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Sample records for fat metabolizing genes

  1. FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness

    DEFF Research Database (Denmark)

    Kring, Sofia I I; Holst, Claus; Zimmermann, Esther

    2008-01-01

    A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already...

  2. Transcription profiling and regulation of fat metabolism genes in diapausing adults of the mosquito Culex pipiens

    Science.gov (United States)

    Sim, Cheolho

    2009-01-01

    Culex pipiens, the mosquito that vectors West Nile virus in North America, overwinters in an adult diapause (dormancy) that is programmed by the short day length and low temperatures of autumn. In response to these environmental signals, females cease feeding on blood and instead seek sources of nectar used to generate the huge lipid reserves required for winter survival. To identify regulatory networks that regulate fat accumulation and fat consumption during diapause, we compared expression of fat-related genes from nondiapausing females with expression of those same genes in early and late diapause and at diapause termination. Among the 31 genes we examined, 4 were expressed more highly in early diapause than in nondiapause, while 14 genes were downregulated in early diapause. In the transition from early to late diapause, 19 genes related to fat metabolism were upregulated. As reported previously, fatty acid synthase, identified as fas-1 in this study, was upregulated in early diapause. Numerous fat metabolism genes, including multiple kinetic classes and genes involved in β-oxidation, an energy-generation step, were suppressed in early diapause but were highly expressed in late diapause and at diapause termination. RNA interference (RNAi) analysis revealed that the fas-1 gene and others (fas-3 and fabp) have important roles in fat storage during early diapause. When expression of these genes is suppressed, female mosquitoes fail to sequester the lipids needed for overwintering. PMID:19706691

  3. Diet-gene interactions between dietary fat intake and common polymorphisms in determining lipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Corella, D.

    2009-07-01

    Current dietary guidelines for fat intake have not taken into consideration the possible genetic differences underlying the individual variability in responsiveness to dietary components. Genetic variability has been identified in humans for all the known lipid metabolism-related genes resulting in a plethora of candidate genes and genetic variants to examine in diet-gene interaction studies focused on fat consumption. Some examples of fat-gene interaction are reviewed. These include: the interaction between total intake and the 14C/T in the hepatic lipase gene promoter in determining high-density lipoprotein cholesterol (HDL-C) metabolism; the interaction between polyunsaturated fatty acids (PUFA) and the 5G/A polymorphism in the APOA1 gene plasma HDL-C concentrations; the interaction between PUFA and the L162V polymorphism in the PPARA gene in determining triglycerides and APOC3 concentrations; and the interaction between PUFA intake and the -1131T>C in the APOA5 gene in determining triglyceride metabolism. Although hundreds of diet-gene interaction studies in lipid metabolism have been published, the level of evidence to make specific nutritional recommendations to the population is still low and more research in nutrigenetics has to be undertaken. (Author) 31 refs.

  4. Effects of abhydrolase domain containing 5 gene (ABHD5) expression and variations on chicken fat metabolism.

    Science.gov (United States)

    Ouyang, Hongjia; Liu, Qing; Xu, Jiguo; Zeng, Fang; Pang, Xiaolin; Jebessa, Endashaw; Liang, Shaodong; Nie, Qinghua; Zhang, Xiquan

    2016-01-01

    Abhydrolase domain containing 5 gene (ABHD5), also known as comparative gene identification 58 (CGI-58), is a member of the α/β-hydrolase family as a protein cofactor of ATGL stimulating its triacylglycerol hydrolase activity. In this study, we aim to characterize the expression and variations of ABHD5 and to study their functions in chicken fat metabolism. We compared the ABHD5 expression level in various tissues and under different nutrition conditions, identified the variations of ABHD5, and associated them with production traits in an F2 resource population of chickens. Overexpression analysis with two different genotypes and siRNA interfering analysis of ABHD5 were performed in chicken preadipocytes. Chicken ABDH5 was expressed widely and most predominantly in adipose tissue. Five SNPs of the ABHD5 gene were identified and genotyped in the F2 resource population. The c.490C > T SNP was associated with subcutaneous fat thickness (P  C SNP was also associated with chicken body weight (P chicken preadipocytes, overexpression of wild type ABDH5 did not affect the mRNA level of ATGL (adipose triglyceride lipase) but markedly decreased (P chickens with a high fat diet. These results suggest that expression and variations of ABHD5 may affect fat metabolism through regulating the activity of ATGL in chickens. © 2015 Poultry Science Association Inc.

  5. RNA-Seq Analysis of Abdominal Fat in Genetically Fat and Lean Chickens Highlights a Divergence in Expression of Genes Controlling Adiposity, Hemostasis, and Lipid Metabolism.

    Directory of Open Access Journals (Sweden)

    Christopher W Resnyk

    Full Text Available Genetic selection for enhanced growth rate in meat-type chickens (Gallus domesticus is usually accompanied by excessive adiposity, which has negative impacts on both feed efficiency and carcass quality. Enhanced visceral fatness and several unique features of avian metabolism (i.e., fasting hyperglycemia and insulin insensitivity mimic overt symptoms of obesity and related metabolic disorders in humans. Elucidation of the genetic and endocrine factors that contribute to excessive visceral fatness in chickens could also advance our understanding of human metabolic diseases. Here, RNA sequencing was used to examine differential gene expression in abdominal fat of genetically fat and lean chickens, which exhibit a 2.8-fold divergence in visceral fatness at 7 wk. Ingenuity Pathway Analysis revealed that many of 1687 differentially expressed genes are associated with hemostasis, endocrine function and metabolic syndrome in mammals. Among the highest expressed genes in abdominal fat, across both genotypes, were 25 differentially expressed genes associated with de novo synthesis and metabolism of lipids. Over-expression of numerous adipogenic and lipogenic genes in the FL chickens suggests that in situ lipogenesis in chickens could make a more substantial contribution to expansion of visceral fat mass than previously recognized. Distinguishing features of the abdominal fat transcriptome in lean chickens were high abundance of multiple hemostatic and vasoactive factors, transporters, and ectopic expression of several hormones/receptors, which could control local vasomotor tone and proteolytic processing of adipokines, hemostatic factors and novel endocrine factors. Over-expression of several thrombogenic genes in abdominal fat of lean chickens is quite opposite to the pro-thrombotic state found in obese humans. Clearly, divergent genetic selection for an extreme (2.5-2.8-fold difference in visceral fatness provokes a number of novel regulatory responses

  6. Dietary fat influences the expression of contractile and metabolic genes in rat skeletal muscle.

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    Wataru Mizunoya

    Full Text Available Dietary fat plays a major role in obesity, lipid metabolism, and cardiovascular diseases. To determine whether the intake of different types of dietary fats affect the muscle fiber types that govern the metabolic and contractile properties of the skeletal muscle, we fed male Wistar rats with a 15% fat diet derived from different fat sources. Diets composed of soybean oil (n-6 polyunsaturated fatty acids (PUFA-rich, fish oil (n-3 PUFA-rich, or lard (low in PUFAs were administered to the rats for 4 weeks. Myosin heavy chain (MyHC isoforms were used as biomarkers to delineate the skeletal muscle fiber types. Compared with soybean oil intake, fish oil intake showed significantly lower levels of the fast-type MyHC2B and higher levels of the intermediate-type MyHC2X composition in the extensor digitorum longus (EDL muscle, which is a fast-type dominant muscle. Concomitantly, MyHC2X mRNA levels in fish oil-fed rats were significantly higher than those observed in the soybean oil-fed rats. The MyHC isoform composition in the lard-fed rats was an intermediate between that of the fish oil and soybean oil-fed rats. Mitochondrial uncoupling protein 3, pyruvate dehydrogenase kinase 4, and porin mRNA showed significantly upregulated levels in the EDL of fish oil-fed rats compared to those observed in soybean oil-fed and lard-fed rats, implying an activation of oxidative metabolism. In contrast, no changes in the composition of MyHC isoforms was observed in the soleus muscle, which is a slow-type dominant muscle. Fatty acid composition in the serum and the muscle was significantly influenced by the type of dietary fat consumed. In conclusion, dietary fat affects the expression of genes related to the contractile and metabolic properties in the fast-type dominant skeletal muscle, where the activation of oxidative metabolism is more pronounced after fish oil intake than that after soybean oil intake.

  7. Dietary Fat, Fat Metabolizing Genes, and Prostate Cancer Risk in African-Americans and Whites

    National Research Council Canada - National Science Library

    Ingles, Sue A

    2004-01-01

    ... African-Americans and whites in Los Angels County. In the first year of the study, we finished genotyping three LOX gene polymorphisms, including 12-LOX G1n261Arg, Ser322Asn, and the 5_LOX promoter Sp1 motif polymorphism...

  8. Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Rehrer, N J; Pilegaard, H

    2007-01-01

    nmol kg(-1) d.w.; n = 7, P lipoprotein lipase and glycogen synthase increased (P ... exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes....

  9. Dietary fat source affects metabolism of fatty acids in pigs as evaluated by altered expression of lipogenic genes in liver and adipose tissues

    DEFF Research Database (Denmark)

    Duran-Montge, P; Theil, Peter Kappel; Lauridsen, Charlotte

    2009-01-01

    Little is known about pig gene expressions related to dietary fatty acids (FAs) and most work have been conducted in rodents. The aim of this study was to investigate how dietary fats regulate fat metabolism of pigs in different tissues. Fifty-six crossbred gilts (62 ± 5.2 kg BW) were fed one...... of seven dietary treatments (eight animals per treatment): a semi-synthetic diet containing a very low level of fat (no fat (NF)) and six fat-supplemented diets (ca. 10%) based on barley and soybean meal. The supplemental fat sources were tallow (T), high-oleic sunflower oil (HOSF), sunflower oil (SFO...

  10. Hepatic gene expression involved in glucose and lipid metabolism in transition cows: effects of fat mobilization during early lactation in relation to milk performance and metabolic changes.

    Science.gov (United States)

    Weber, C; Hametner, C; Tuchscherer, A; Losand, B; Kanitz, E; Otten, W; Sauerwein, H; Bruckmaier, R M; Becker, F; Kanitz, W; Hammon, H M

    2013-09-01

    Insufficient feed intake during early lactation results in elevated body fat mobilization to meet energy demands for milk production. Hepatic energy metabolism is involved by increasing endogenous glucose production and hepatic glucose output for milk synthesis and by adaptation of postcalving fuel oxidation. Given that cows differ in their degree of fat mobilization around parturition, indicated by variable total liver fat concentration (LFC), the study investigated the influence of peripartum fat mobilization on hepatic gene expression involved in gluconeogenesis, fatty acid oxidation, ketogenesis, and cholesterol synthesis, as well as transcriptional factors referring to energy metabolism. German Holstein cows were grouped according to mean total LFC on d 1, 14, and 28 after parturition as low [300 mg of total fat/g of DM; n=7), indicating fat mobilization during early lactation. Cows were fed total mixed rations ad libitum and held under equal conditions. Liver biopsies were taken at d 56 and 15 before and d 1, 14, 28, and 49 after parturition to measure mRNA abundances of pyruvate carboxylase (PC); phosphoenolpyruvate carboxykinase; glucose-6-phosphatase; propionyl-coenzyme A (CoA) carboxylase α; carnitine palmitoyl-transferase 1A (CPT1A); acyl-CoA synthetase, long chain 1 (ASCL1); acyl-CoA dehydrogenase, very long chain; 3-hydroxy-3-methylglutaryl-CoA synthase 1 and 2; sterol regulatory element-binding factor 1; and peroxisome proliferator-activated factor α. Total LFC postpartum differed greatly among cows, and the mRNA abundance of most enzymes and transcription factors changed with time during the experimental period. Abundance of PC mRNA increased at parturition to a greater extent in high- and medium-LFC groups than in the low-LFC group. Significant LFC × time interactions for ACSL1 and CPT1A during the experimental period indicated variable gene expression depending on LFC after parturition. Correlations between hepatic gene expression and

  11. Polymorphism of fat metabolism genes as candidate markers for meat quality and production traits in heavy pigs.

    Science.gov (United States)

    Renaville, B; Bacciu, N; Lanzoni, M; Corazzin, M; Piasentier, E

    2015-12-01

    High meat quality is required for dry-cured ham production, which quality depends on meat fat quantity and composition. The aim was to study the polymorphisms of six genes involved in fat metabolism, namely, Stearoyl-CoA desaturase (SCD), Diacylglycerol acyltransferase 1 and 2 (DGAT1 &DGAT2), Microsomal triglyceride transfer protein (MTTP), Fatty acid synthase (FASN) and Heart fatty acid binding protein (H-FABP) in two traditional (Large White or Duroc × (Landrace × Large White)) and two industrial hybrids (Goland and Danbred), which are used for dry-cured ham production. Significant associations of SCD and MTTP were found with carcass weight. DGAT2 was associated with back fat thickness and L* fat colour (objective white colour score). Several genes (DGAT2, MTTP &FASN) were associated with weight loss during salting, first step in dry-cured ham production, affecting final yield. Finally, MTTP was associated with shear force. Our findings suggest that the SCD, DGAT2, MTTP and FASN polymorphisms are associated with quality of heavy pig meat products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice.

    Science.gov (United States)

    Kandasamy, A D; Sung, M M; Boisvenue, J J; Barr, A J; Dyck, J R B

    2012-09-10

    Adiponectin is an adipokine secreted primarily from adipose tissue that can influence circulating plasma glucose and lipid levels through multiple mechanisms involving a variety of organs. In humans, reduced plasma adiponectin levels induced by obesity are associated with insulin resistance and type 2 diabetes, suggesting that low adiponectin levels may contribute the pathogenesis of obesity-related insulin resistance. The objective of the present study was to investigate whether gene therapy designed to elevate circulating adiponectin levels is a viable strategy for ameliorating insulin resistance in mice fed a high-fat, high-sucrose (HFHS) diet. Electroporation-mediated gene transfer of mouse adiponectin plasmid DNA into gastrocnemius muscle resulted in elevated serum levels of globular and high-molecular weight adiponectin compared with control mice treated with empty plasmid. In comparison to HFHS-fed mice receiving empty plasmid, mice receiving adiponectin gene therapy displayed significantly decreased weight gain following 13 weeks of HFHS diet associated with reduced fat accumulation, and exhibited increased oxygen consumption and locomotor activity as measured by indirect calorimetry, suggesting increased energy expenditure in these mice. Consistent with improved whole-body metabolism, mice receiving adiponectin gene therapy also had lower blood glucose and insulin levels, improved glucose tolerance and reduced hepatic gluconeogenesis compared with control mice. Furthermore, immunoblot analysis of livers from mice receiving adiponectin gene therapy showed an increase in insulin-stimulated phosphorylation of insulin signaling proteins. Based on these data, we conclude that adiponectin gene therapy ameliorates the metabolic abnormalities caused by feeding mice a HFHS diet and may be a potential therapeutic strategy to improve obesity-mediated impairments in insulin sensitivity.

  13. Fat metabolism is regulated by altered gene expression oflipogenic enzymes and regulatory factors in liver and adiposetissue but not in semimembranosus muscle of pigs during thefattening period

    DEFF Research Database (Denmark)

    Duran-Montge, P; Theil, Peter Kappel; Lauridsen, Charlotte

    2009-01-01

    It has been shown previously that lipid metabolism is regulated by fatty acids (FA) and that thyroid hormones are important regulators of energy metabolism. The effects of weight, dietary fat level and dietary FA profile on thyroid hormone levels and expression of lipogenic genes and tissue FA......, in particular, in regulating whole animal fat metabolism, with effects brought about by altered expression of lipogenic genes. Liver sterol receptor element binding protein-1 (SREBP1) mRNA content was affected by dietary treatment ( P,0.001) and was correlated with ACACA and SCD, whereas adipose tissue SREBP1...... was not correlated with the mRNA abundance of any lipogenic enzyme. Weight and tissue factors showed greater influence on mRNA abundance of genes related with lipid metabolism than diet and tissue FA composition. In the pig, FA synthesis appear to be of greater magnitude in adipose tissue than in the liver...

  14. Transgenesis of humanized fat1 promotes n-3 polyunsaturated fatty acid synthesis and expression of genes involved in lipid metabolism in goat cells.

    Science.gov (United States)

    Fan, Yixuan; Ren, Caifang; Wang, Zhibo; Jia, Ruoxin; Wang, Dan; Zhang, Yanli; Zhang, Guomin; Wan, Yongjie; Huang, Mingrui; Wang, Feng

    2016-01-15

    The n-3 fatty acid desaturase gene fat1 codes for the n-3 desaturase enzyme, which can convert n-6 polyunsaturated fatty acids (PUFAs) to n-3 PUFAs. The n-3 PUFAs are essential components required for normal cellular function and have preventive and therapeutic effects on many diseases. Goat is an important domestic animal for human consumption of meat and milk. To elevate the concentrations of n-3 PUFAs and examine the regulatory mechanism of fat1 in PUFA metabolism in goat cells, we successfully constructed a humanized fat1 expression vector and confirmed the efficient expression of fat1 in goat ear skin-derived fibroblast cells (GEFCs) by qRT-PCR and Western blot analysis. Fatty acid analysis showed that fat1 overexpression significantly increased the levels of total n-3 PUFAs and decreased the levels of total n-6 PUFAs in GEFCs. In addition, qRT-PCR results indicate that the FADS1 and FADS2 desaturase genes, ELOV2 and ELOV5 elongase genes, ACO and CPT1 oxidation genes, and PPARa and PPARγ transcription factors are up-regulated, and transcription factors of SREBP-1c gene are down-regulated in the fat1 transgenic goat cells. Overall, fat1-overexpression resulted in an increase in the n-3 fatty acids and altered expression of PUFA synthesis related genes in GEFCs. This work lays a foundation for both the production of fat1 transgenic goats and further study of the mechanism of fat1 function in the PUFAs metabolism. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Eicosapentaenoic acid regulates brown adipose tissue gene expression and metabolism in high fat fed mice

    Science.gov (United States)

    Brown adipose tissue (BAT) is a thermogenic tissue, a key regulator of energy balance and a potential therapeutic target for obesity. We previously reported that eicosapentaenoic acid (EPA) reduced high fat (HF) diet-induced obesity and insulin resistance in mice, independent of energy intake. We hy...

  16. De novo cloning and annotation of genes associated with immunity, detoxification and energy metabolism from the fat body of the oriental fruit fly, Bactrocera dorsalis.

    Directory of Open Access Journals (Sweden)

    Wen-Jia Yang

    Full Text Available The oriental fruit fly, Bactrocera dorsalis, is a destructive pest in tropical and subtropical areas. In this study, we performed transcriptome-wide analysis of the fat body of B. dorsalis and obtained more than 59 million sequencing reads, which were assembled into 27,787 unigenes with an average length of 591 bp. Among them, 17,442 (62.8% unigenes matched known proteins in the NCBI database. The assembled sequences were further annotated with gene ontology, cluster of orthologous group terms, and Kyoto encyclopedia of genes and genomes. In depth analysis was performed to identify genes putatively involved in immunity, detoxification, and energy metabolism. Many new genes were identified including serpins, peptidoglycan recognition proteins and defensins, which were potentially linked to immune defense. Many detoxification genes were identified, including cytochrome P450s, glutathione S-transferases and ATP-binding cassette (ABC transporters. Many new transcripts possibly involved in energy metabolism, including fatty acid desaturases, lipases, alpha amylases, and trehalose-6-phosphate synthases, were identified. Moreover, we randomly selected some genes to examine their expression patterns in different tissues by quantitative real-time PCR, which indicated that some genes exhibited fat body-specific expression in B. dorsalis. The identification of a numerous transcripts in the fat body of B. dorsalis laid the foundation for future studies on the functions of these genes.

  17. De novo Cloning and Annotation of Genes Associated with Immunity, Detoxification and Energy Metabolism from the Fat Body of the Oriental Fruit Fly, Bactrocera dorsalis

    Science.gov (United States)

    Yang, Wen-Jia; Yuan, Guo-Rui; Cong, Lin; Xie, Yi-Fei; Wang, Jin-Jun

    2014-01-01

    The oriental fruit fly, Bactrocera dorsalis, is a destructive pest in tropical and subtropical areas. In this study, we performed transcriptome-wide analysis of the fat body of B. dorsalis and obtained more than 59 million sequencing reads, which were assembled into 27,787 unigenes with an average length of 591 bp. Among them, 17,442 (62.8%) unigenes matched known proteins in the NCBI database. The assembled sequences were further annotated with gene ontology, cluster of orthologous group terms, and Kyoto encyclopedia of genes and genomes. In depth analysis was performed to identify genes putatively involved in immunity, detoxification, and energy metabolism. Many new genes were identified including serpins, peptidoglycan recognition proteins and defensins, which were potentially linked to immune defense. Many detoxification genes were identified, including cytochrome P450s, glutathione S-transferases and ATP-binding cassette (ABC) transporters. Many new transcripts possibly involved in energy metabolism, including fatty acid desaturases, lipases, alpha amylases, and trehalose-6-phosphate synthases, were identified. Moreover, we randomly selected some genes to examine their expression patterns in different tissues by quantitative real-time PCR, which indicated that some genes exhibited fat body-specific expression in B. dorsalis. The identification of a numerous transcripts in the fat body of B. dorsalis laid the foundation for future studies on the functions of these genes. PMID:24710118

  18. Concurrence of High Fat Diet and APOE Gene Induces Allele Specific Metabolic and Mental Stress Changes in an AD Model

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    Yifat Segev

    2016-09-01

    Full Text Available Aging is the main risk factor for neurodegenerative diseases, including Alzheimer’s disease (AD. However, evidence indicates that the pathological process begins long before actual cognitive or pathological symptoms are apparent. The long asymptomatic phase and complex integration between genetic, environmental, and metabolic factors make it one of the most challenging diseases to understand and cure. In the present study, we asked whether an environmental factor such as high-fat diet would synergize with a genetic factor to affect the metabolic and cognitive state in the ApoE4 mouse model of AD. Our data suggest that a high-fat diet induces diabetes mellitus-like metabolism in ApoE4 mice, as well as changes in BACE1 protein levels between the two ApoE strains. Furthermore, high-fat diet induces anxiety in this AD mouse model. Our results suggest that young ApoE4 carriers are prone to psychological stress and metabolic abnormalities related to AD, which can easily be triggered via high-fat nutrition.

  19. Individual Responsiveness to Exercise-Induced Fat Loss and Improvement of Metabolic Profile in Young Women is Associated with Polymorphisms of Adrenergic Receptor Genes

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    Agata Leońska-Duniec, Zbigniew Jastrzębski, Aleksandra Jażdżewska, Waldemar Moska, Ewelina Lulińska-Kuklik, Marek Sawczuk, Svetlana I. Gubaydullina, Alsu T. Shakirova, Pawel Cięszczyk, Adam Maszczyk, Ildus I. Ahmetov

    2018-03-01

    Full Text Available The effectiveness of physical exercise on fat loss and improvement of aerobic capacity varies considerably between individuals. A strong linkage exists between common allelic variants of the adrenergic receptor genes and weight gain, as well as changes in body composition. Therefore we aimed to check if body composition and metabolic variables were modulated by the ADRB2 (Gly16Arg and Glu27Gln, ADRB3 (Trp64Arg and ADRA2A (rs553668 G/A gene polymorphisms in 163 Polish sedentary women (age 19-24; body mass index (BMI 21.7 ± 0.2 kg·m-2 involved in a 12-week aerobic training program. Only 74.8% of participants lost fat mass. On average, participants lost 5.8 (10.4% of their relative fat mass with training (range: +28.3 to -63.6%. The improvement of VO2max was significantly greater in women who could lose their fat mass compared to women who were unsuccessful in fat loss (4.5 (5.6% vs. 1.5 (3.8%; p = 0.0045. The carriers of a low number (0-3 of obesity-related risk alleles (ADRB2 Gly16, ADRB2 Glu27, ADRA2A rs553668 G were more successful in fat mass loss compared to the carriers of a high number (5-6 of risk alleles (7.7 (9.8 vs 4.0 (9.4%, p = 0.0362. The presented results support the assumption that variation within adrenergic receptor genes contributes to interindividual changes of body composition in response to physical exercise.

  20. MiR-27a suppresses triglyceride accumulation and affects gene mRNA expression associated with fat metabolism in dairy goat mammary gland epithelial cells.

    Science.gov (United States)

    Lin, Xian-Zi; Luo, Jun; Zhang, Li-Ping; Wang, Wei; Shi, Heng-Bo; Zhu, Jiang-Jiang

    2013-05-25

    MicroRNAs (miRNAs), a well-defined group of small RNAs containing about 22 nucleotides, participate in various biological metabolic processes. miR-27a is a miRNA that is known to regulate fat synthesis and differentiation in preadipocyte cells. However, little is known regarding the role that miR-27a plays in regulating goat milk fat synthesis. In this study, we determined the miR-27a expression profile in goat mammary gland and found that miR-27a expression was correlated with the lactation cycle. Additionally, prolactin promoted miR-27a expression in goat mammary gland epithelial cells. Further functional analysis showed that over-expression of miR-27a down-regulated triglyceride accumulation and decreased the ratio of unsaturated/saturated fatty acid in mammary gland epithelial cells. miR-27a also significantly affected mRNA expression related to milk fat metabolism. Specifically, over-expression of miR-27a reduced gene mRNA expression associated with triglyceride synthesis by suppressing PPARγ protein levels. This study provides the first experimental evidence that miR-27a regulates triglyceride synthesis in goat mammary gland epithelial cells and improves our understanding about the importance of miRNAs in milk fat synthesis. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  1. Variable liver fat concentration as a proxy for body fat mobilization postpartum has minor effects on insulin-induced changes in hepatic gene expression related to energy metabolism in dairy cows.

    Science.gov (United States)

    Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Bruckmaier, R M; Röntgen, M; Kuhla, B; Hammon, H M

    2017-02-01

    The liver plays a central role in adaptation for energy requirements around calving, and changes in the effects of insulin on hepatic energy metabolism contribute to metabolic adaptation in dairy cows. Hepatic insulin effects may depend on body fat mobilization. The objective of this study was to investigate the effects of insulin on the hepatic gene expression of enzymes involved in energy metabolism and factors related to nutrition partitioning in cows with high and low total liver fat concentration (LFC) after calving. Holstein cows were retrospectively grouped according to their LFC after calving as a proxy for body fat mobilization. Cows were classified as low (LLFC; LFC 24.4% fat/dry matter; n = 10) fat-mobilizing after calving. Euglycemic-hyperinsulinemic clamps [6 mU/(kg × min) of insulin for 6 h] were performed in wk 5 antepartum (ap) and wk 3 postpartum (pp). Before and at the end of the euglycemic-hyperinsulinemic clamps, liver biopsies were taken to measure the mRNA abundance of enzymes involved in carbohydrate and lipid metabolism, expression related to the somatotropic axis, and adrenergic and glucocorticoid receptors. The mRNA abundance of pyruvate carboxylase, cytosolic phosphoenolpyruvate carboxykinase (PEPCK; PCK1), acyl-CoA-dehydrogenase very long chain (ACADVL), and hydroxyl-methyl-glutaryl-CoA-synthase 1 increased, but the mRNA abundance of solute carrier family 2 (SLC2A2 and SLC2A4), growth hormone receptor 1A (GHR1A), insulin-like growth factor 1 (IGF1), sterol regulatory element binding factor 1, adrenoceptor α 1A, and glucocorticoid receptor decreased from ap to pp. Insulin treatment was associated with decreased PCK1, mitochondrial PEPCK, glucose-6-phosphatase, propionyl-CoA-carboxylase α, carnitine-palmitoyl-transferase 1A, ACADVL, and insulin receptor mRNA, but increased IGF1 and SLC2A4 mRNA ap and pp and GHR1A mRNA pp. The mRNA abundance of SLC2A4 was greater, and the mRNA abundance of GHR1A and IGF1 tended to be lower in LLFC than

  2. Comparison of glucose and lipid metabolic gene expressions between fat and lean lines of rainbow trout after a glucose load.

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    Junyan Jin

    Full Text Available Two experimental rainbow trout lines developed through divergent selection for low (Lean 'L' line or high (Fat 'F' line muscle fat content were used as models to study the genetic determinism of fat depots. Previous nutritional studies suggested that the F line had a better capability to use glucose than the L line during feeding trials. Based on that, we put forward the hypothesis that F line has a greater metabolic ability to clear a glucose load effectively, compared to L line. In order to test this hypothesis, 250 mg/kg glucose was intraperitoneally injected to the two rainbow trout lines fasted for 48 h. Hyperglycemia was observed after glucose treatment in both lines without affecting the phosphorylation of AMPK (cellular energy sensor and Akt-TOR (insulin signaling components. Liver glucokinase and glucose-6-phosphate dehydrogenase expression levels were increased by glucose, whereas mRNA levels of β-oxidation enzymes (CPT1a, CPT1b, HOAD and ACO were down-regulated in the white skeletal muscle of both lines. Regarding the genotype effect, concordant with normoglycemia at 12 h after glucose treatment, higher muscle glycogen was found in F line compared to L line which exhibited hyperglycemia. Moreover, mRNA levels of hepatic glycolytic enzymes (GK, 6PFK and PK, gluconeogenic enzyme PEPCK and muscle fatty acid oxidation enzymes (CPT1a, CPT1b and HOAD were concurrently higher in the F line. Overall, these findings suggest that F line may have a better ability to maintain glucose homeostasis than L line.

  3. Red pitaya juice supplementation ameliorates energy balance homeostasis by modulating obesity-related genes in high-carbohydrate, high-fat diet-induced metabolic syndrome rats.

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    Ramli, Nurul Shazini; Ismail, Patimah; Rahmat, Asmah

    2016-07-26

    Red pitaya (Hylocereus polyrhizus) or known as buah naga merah in Malay belongs to the cactus family, Cactaceae. Red pitaya has been shown to give protection against liver damage and may reduce the stiffness of the heart. Besides, the beneficial effects of red pitaya against obesity have been reported; however, the mechanism of this protection is not clear. Therefore, in the present study, we have investigated the red pitaya-targeted genes in obesity using high-carbohydrate, high-fat diet-induced metabolic syndrome rat model. A total of four groups were tested: corn-starch (CS), corn-starch + red pitaya juice (CRP), high-carbohydrate, high-fat (HCHF) and high-carbohydrate, high-fat + red pitaya juice (HRP). The intervention with 5 % red pitaya juice was continued for 8 weeks after 8 weeks initiation of the diet. Retroperitoneal, epididymal and omental fat pads were collected and weighed. Plasma concentration of IL-6 and TNF-α were measured using commercial kits. Gene expression analysis was conducted using RNA extracted from liver samples. A total of eighty-four genes related to obesity were analyzed using PCR array. The rats fed HCHF-diet for 16 weeks increased body weight, developed excess abdominal fat deposition and down-regulated the expression level of IL-1α, IL-1r1, and Cntfr as compared to the control group. Supplementation of red pitaya juice for 8 weeks increased omental and epididymal fat but no change in retroperitoneal fat was observed. Red pitaya juice reversed the changes in energy balance homeostasis in liver tissues by regulation of the expression levels of Pomc and Insr. The increased protein expression levels of IL-6 and TNF-α in HCHF group and red pitaya treated rats confirmed the results of gene expression. Collectively, this study revealed the usefulness of this diet-induced rat model and the beneficial effects of red pitaya on energy balance homeostasis by modulating the anorectic, orexigenic and energy expenditure related

  4. A high fat diet does not affect the iron bioavailability in Wistar rats fed with chia and increases gene expression of iron metabolism proteins.

    Science.gov (United States)

    da Silva, Bárbara Pereira; Matyelka, Jéssika Camila da Silva; Moreira, Maria Eliza de Castro; Toledo, Renata Celi Lopes; Della Lucia, Ceres Mattos; Pinheiro-Sant'Ana, Helena Maria; Martino, Hércia Stampini Duarte

    2016-12-07

    This study evaluated the effect of chia on the iron bioavailability and gene expression of proteins involved in iron metabolism in animals fed with a high fat diet and a standard diet. Four experimental groups were tested (n = 8): standard diet + ferrous sulfate (SD + FS), standard diet + chia (SD + C), high fat diet + ferrous sulfate (HFD + FS), high fat diet + chia (HFD + C). The hemoglobin gain, hemoglobin regeneration efficiency, biological relative value of HRE, serum ferritin and transferrin, liver iron concentration and gene expression of proteins were evaluated. The SD + C group showed lower transferrin expression when compared to the control group. The control group showed serum transferrin concentration higher than the other groups. Serum ferritin and liver iron concentration did not differ among the animals that received chia ferritin and hephaestin expression was lower in experimental groups when compared with the control group. The peroxisome proliferator activated receptor expression was higher in animals fed with SD + C than in the control group. The expression of duodenal cytochrome B and divalent metal transporter 1 in the HFD + C group was higher and ferroportin was lower in the groups containing chia. Animals fed with chia showed similar iron bioavailability compared to animals fed with ferrous sulfate.

  5. Voluntary exercise and green tea enhance the expression of genes related to energy utilization and attenuate metabolic syndrome in high fat fed mice.

    Science.gov (United States)

    Sae-Tan, Sudathip; Rogers, Connie J; Lambert, Joshua D

    2014-05-01

    Obesity and metabolic syndrome are growing public health problems. We investigated the effects of decaffeinated green tea extract (GTE) and voluntary running exercise (Ex) alone or in combination against obesity and metabolic syndrome in high fat (HF) fed C57BL/6J mice. After 16 wk, GTE + Ex treatment reduced final body mass (27.1% decrease) and total visceral fat mass (36.6% decrease) compared to HF-fed mice. GTE + Ex reduced fasting blood glucose (17% decrease), plasma insulin (65% decrease), and insulin resistance (65% decrease) compared to HF-fed mice. GTE or Ex alone had less significant effects. In the skeletal muscle, the combination of Ex and GTE increased the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (Ppargc1a), mitochondrial NADH dehydrogenase 5 (mt-Nd5), mitochondrial cytochrome b (mt-Cytb), and mitochondrial cytochrome c oxidase III (mt-Co3). An increase in hepatic expression of peroxisome proliferator-activated receptor-α (Ppara) and liver carnitine palmitoyl transferase-1α (Cpt1a) and a decrease in hepatic expression of stearoyl-CoA desaturase 1 (Scd1) mRNA was observed in GTE + Ex mice. GTE + Ex was more effective than either treatment alone in reducing diet-induced obesity. These effects are due in part to modulation of genes related to energy metabolism and de novo lipogenesis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Effects of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in bovine mammary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Hongyun Liu

    Full Text Available As the main precursor for lactose synthesis, large amounts of glucose are required by lactating dairy cows. Milk yield greatly depends on mammary lactose synthesis due to its osmoregulatory property for mammary uptake of water. Thus, glucose availability to the mammary gland could be a potential regulator of milk production. In the present study, the effect of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in vitro was investigated. Bovine mammary epithelial cells (BMEC were treated for 12 h with various concentrations of glucose (2.5, 5, 10 or 20 mmol/L. The higher concentrations of glucose (10-20 mmol/L did not affect the mRNA expression of acetyl-CoA carboxylase, diacyl glycerol acyl transferase, glycerol-3 phosphate acyl transferase and α-lactalbumin, whereas fatty acid synthase, sterol regulatory element binding protein-1 and beta-1, 4-galactosyl transferase mRNA expression increased at 10 mmol/L and then decreased at 20 mmol/L. The content of lactose synthase increased with increasing concentration of glucose, with addition of highest value at 20 mmol/L of glucose. Moreover, the increased glucose concentration stimulated the activities of pyruvate kinase and glucose-6-phosphate dehydrogenase, and elevated the energy status of the BMEC. Therefore, it was deduced that after increasing glucose availability, the extra absorbed glucose was partitioned to entering the synthesis of milk fat and lactose by the regulation of the mRNA expression of key genes, promoting glucose metabolism by glycolysis and pentose phosphate pathway as well as energy status. These results indicated that the sufficient availability of glucose in BMEC may promote glucose metabolism, and affect the synthesis of milk composition.

  7. NF-E2-related factor 2 deletion facilitates hepatic fatty acids metabolism disorder induced by high-fat diet via regulating related genes in mice.

    Science.gov (United States)

    Wang, Xinghe; Li, Chunyan; Xu, Shang; Ishfaq, Muhammad; Zhang, Xiuying

    2016-08-01

    There is increasing evidence that Nrf2 participates in hepatic fatty acid metabolism in non-alcoholic fatty liver disease; however, the mechanism remains unclear. We investigated the role of Nrf2 in hepatic fatty acid metabolism disorder induced by high-fat diet (HFD). Mice fed HFD developed hepatic steatosis and exhibited Nrf2 deficiency. Change of fatty acid composition mediated by Nrf2 deletion was observed predominantly in the liver and not the serum. HFD-induced variations in hepatic 18-carbon and 22-carbon fatty acids were enhanced by Nrf2 deficiency. In the HFD group, Nrf2 deficiency led to increases in the mRNA expression of PPARα, FXR, FAS, LXR and ACC-1, while levels of PGC-1α and Srebp-1c mRNA were decreased. Nrf2 mRNA expression was enhanced in the liver of HFD-induced wild type mice, whereas it was undetectable in Nrf2-null mice. These results suggest that Nrf2 deficiency induced by HFD promoted hepatic fatty acid metabolism disorder by altering 18-carbon and 22-carbon fatty acid composition. Changes in fatty acid content were also associated with alteration of the transcription of genes involved in hepatic fatty acid metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Relation of -55CT polymorphism of UCP3 gene with weight loss and metabolic changes after a high monounsaturated fat diet in obese non diabetic patients.

    Science.gov (United States)

    De Luis, D A; Aller, R; Izaola, O; De La Fuente, B; Conde, R; Eiros Bouza, J M

    2013-10-01

    The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on metabolic response, weight loss and serum adipokine levels to a high monounsaturated fat hypocaloric diet in obese patients. A sample of 128 obese patients was analyzed in a prospective way during 3 months. Eighty eight patients (21 males/67 females) (68.8%) had the genotype 55CC (wild genotype group) and 40 patients (8 males/32 females) (31.3%) 55CT (mutant genotype group). In wild genotype group, BMI (-1.6±1.3 kg/m2), weight (-4.3±3.7 kg), fat mass (-3.5±3.3 kg), waist circumference (-5.1±2.9 cm), total cholesterol (-7.2±10.6 mg/dl), LDL cholesterol (-5.3±12.8 mg/dl) and leptin (-4.7±10.1 ng/ml) decreased. In mutant genotype group, BMI (1.3±2.2 kg/m2), weight (-3.0±1.4 kg), fat mass (-2.5±1.1 kg), waist circumference (-2.8±3.1 cm) and leptin (-5.8±10.7 decreased. In patients with -55CC UCP3 genotype, a high mono-unsaturated hypocaloric diet reduced BMI, weight, waist circumference, waist to hip ratio, fat mass, LDL-cholesterol, total cholesterol and leptin levels. Carriers of T allele had a different response than -55CC patients, with a significant decrease of the same antropometric parameters, but lower than in the wild genotype group, and without significant changes in cholesterol levels.

  9. Cooked rice prevents hyperlipidemia in hamsters fed a high-fat/cholesterol diet by the regulation of the expression of hepatic genes involved in lipid metabolism.

    Science.gov (United States)

    Choi, Won Hee; Gwon, So Young; Ahn, Jiyun; Jung, Chang Hwa; Ha, Tae Youl

    2013-07-01

    Rice has many health-beneficial components for ameliorating obesity, diabetes, and dyslipidemia. However, the effect of cooked rice as a useful carbohydrate source has not been investigated yet; so we hypothesized that cooked rice may have hypolipidemic effects. In the present study, we investigated the effect of cooked rice on hyperlipidemia and on the expression of hepatic genes involved in lipid metabolism. Golden Syrian hamsters were divided into 2 groups and fed a high-fat (15%, wt/wt)/cholesterol (0.5%, wt/wt) diet supplemented with either corn starch (HFD, 54.5% wt/wt) or cooked rice (HFD-CR, 54.5% wt/wt) as the main carbohydrate source for 8 weeks. In the HFD-CR group, the triglyceride and total cholesterol levels in the serum and liver were decreased, and the total lipid, total cholesterol, and bile acid levels in the feces were increased, compared with the HFD group. In the cooked-rice group, the messenger RNA and protein levels of 3-hydroxy-3-methylglutaryl CoA reductase were significantly downregulated; and the messenger RNA and protein levels of the low-density lipoprotein receptor and cholesterol-7α-hydroxylase were upregulated. Furthermore, the expressions of lipogenic genes such as sterol response element binding protein-1, fatty acid synthase, acetyl CoA carboxylase, and stearoyl CoA desaturase-1 were downregulated, whereas the β-oxidation related genes (carnitine palmitoyl transferase-1, acyl CoA oxidase, and peroxisome proliferator-activated receptor α) were upregulated, in the cooked-rice group. Our results suggest that the hypolipidemic effect of cooked rice is partially mediated by the regulation of hepatic genes involved in lipid metabolism, which results in the suppression of cholesterol and fatty acid synthesis and the enhancement of cholesterol excretion and fatty acid β-oxidation. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Mechanisms and Metabolic Implications of Regional Differences among Fat Depots

    Science.gov (United States)

    Zhu, Yi; Karagiannides, Iordanes; Pothoulakis, Charalabos; Jensen, Michael D.; Kirkland, James L.

    2014-01-01

    Fat distribution is closely linked to metabolic disease risk. Distribution varies with sex, genetic background, disease state, certain drugs and hormones, development, and aging. Preadipocyte replication and differentiation, developmental gene expression, susceptibility to apoptosis and cellular senescence, vascularity, inflammatory cell infiltration, and adipokine secretion vary among depots, as do fatty-acid handling and mechanisms of enlargement with positive-energy and loss with negative-energy balance. How interdepot differences in these molecular, cellular, and pathophysiological properties are related is incompletely understood. Whether fat redistribution causes metabolic disease or whether it is a marker of underlying processes that are primarily responsible is an open question. PMID:23583168

  11. Fat-soluble micronutrients and metabolic syndrome

    Science.gov (United States)

    Goncalves, Aurélie; Amiot, Marie-Josèphe

    2017-01-01

    Purpose of review Metabolic syndrome (MetS) is associated with increased risk of obesity, type 2 diabetes mellitus and cardiovascular diseases. MetS prevalence has been associated with diet inadequacy. Conversely, the cumulative incidence of MetS has been inversely associated with a Mediterranean-style diet that includes many different health-beneficial nutrients. Adherence to a Mediterranean-style diet could reduce or at least stabilize metabolic risk factors. Recent findings Low serum level of fat-soluble micronutrients, such as carotenoids, vitamin (vit) A, D and E, has been linked to MetS. Fat-soluble micronutrients could contribute to prevent MetS thanks to their antioxidant and anti-inflammatory properties (vit E, carotenoids) or to their central role as hormone regulators (vit D) and/or lipid metabolism and glucose homeostasis sensors (vit D and E). Summary This review summarizes recent epidemiological studies linking fat-soluble micronutrients to MetS and highlights new evidence on their mechanisms of actions. PMID:28858890

  12. Responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes: a randomized trial.

    Directory of Open Access Journals (Sweden)

    Susan J van Dijk

    Full Text Available The ability of subjects to respond to nutritional challenges can reflect the flexibility of their biological system. Nutritional challenge tests could be used as an indicator of health status but more knowledge on metabolic and immune responses of different subjects to nutritional challenges is needed. The aim of this study was to compare the responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes.In a cross-over design 42 men (age 50-70 y consumed three high-fat shakes containing saturated fat (SFA, monounsaturated fat (MUFA or n-3 polyunsaturated (PUFA. Men were selected on BMI and health status (lean, obese or obese diabetic and phenotyped with MRI for adipose tissue distribution. Before and 2 and 4 h after shake consumption blood was drawn for measurement of expression of metabolic and inflammation-related genes in peripheral blood mononuclear cells (PBMCs, plasma triglycerides (TAG, glucose, insulin, cytokines and ex vivo PBMC immune response capacity. The MUFA and n-3 PUFA challenge, compared to the SFA challenge, induced higher changes in expression of inflammation genes MCP1 and IL1β in PBMCs. Obese and obese diabetic subjects had different PBMC gene expression and metabolic responses to high-fat challenges compared to lean subjects. The MUFA challenge induced the most pronounced TAG response, mainly in obese and obese diabetic subjects.The PBMC gene expression response and metabolic response to high-fat challenges were affected by fat type and metabolic risk phenotype. Based on our results we suggest using a MUFA challenge to reveal differences in response capacity of subjects.ClinicalTrials.gov NCT00977262.

  13. Beneficial effect of CLOCK gene polymorphism rs1801260 in combination with low-fat diet on insulin metabolism in the patients with metabolic syndrome

    Science.gov (United States)

    Genetic variation at the Circadian Locomotor Output Cycles Kaput (CLOCK) locus has been associated with lifestyle-related conditions such as obesity, metabolic syndrome (MetS) and cardiovascular diseases. In fact, it has been suggested that the disruption of the circadian system may play a causal ro...

  14. Transcriptomic coordination in the human metabolic network reveals links between n-3 fat intake, adipose tissue gene expression and metabolic health.

    Science.gov (United States)

    Morine, Melissa J; Tierney, Audrey C; van Ommen, Ben; Daniel, Hannelore; Toomey, Sinead; Gjelstad, Ingrid M F; Gormley, Isobel C; Pérez-Martinez, Pablo; Drevon, Christian A; López-Miranda, Jose; Roche, Helen M

    2011-11-01

    Understanding the molecular link between diet and health is a key goal in nutritional systems biology. As an alternative to pathway analysis, we have developed a joint multivariate and network-based approach to analysis of a dataset of habitual dietary records, adipose tissue transcriptomics and comprehensive plasma marker profiles from human volunteers with the Metabolic Syndrome. With this approach we identified prominent co-expressed sub-networks in the global metabolic network, which showed correlated expression with habitual n-3 PUFA intake and urinary levels of the oxidative stress marker 8-iso-PGF(2α). These sub-networks illustrated inherent cross-talk between distinct metabolic pathways, such as between triglyceride metabolism and production of lipid signalling molecules. In a parallel promoter analysis, we identified several adipogenic transcription factors as potential transcriptional regulators associated with habitual n-3 PUFA intake. Our results illustrate advantages of network-based analysis, and generate novel hypotheses on the transcriptomic link between habitual n-3 PUFA intake, adipose tissue function and oxidative stress.

  15. Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model.

    Science.gov (United States)

    Park, Se Eun; Park, Cheol-Young; Choi, Jung Mook; Chang, Eugene; Rhee, Eun-Jung; Lee, Won-Young; Oh, Ki Won; Park, Sung Woo; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo

    2016-01-01

    Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.

  16. Metabolic implications of body fat distribution.

    Science.gov (United States)

    Björntorp, P

    1991-12-01

    Insulin resistance is the cornerstone for the development of non-insulin-dependent diabetes mellitus (NIDDM). Free fatty acids (FFAs) cause insulin resistance in muscle and liver and increase hepatic gluconeogenesis and lipoprotein production and perhaps decrease hepatic clearance of insulin. It is suggested that the depressing effect of insulin on circulating FFA concentration is dependent on the fraction derived from visceral adipocytes, which have a low responsiveness to the antilipolytic effect of insulin. Elevated secretion of cortisol and/or testosterone induces insulin resistance in muscle. This also seems to be the case for low testosterone concentrations in men. In addition, cortisol increases hepatic gluconeogenesis. Cortisol and testosterone have "permissive" effect on adipose lipolysis and therefore amplify lipolytic stimulation; FFA, cortisol, and testosterone thus have powerful combined effects, resulting in insulin resistance and increased hepatic gluconeogenesis. All these factors promoting insulin resistance are active in abdominal visceral obesity, which is closely associated with insulin resistance, NIDDM, and the "metabolic syndrome." In addition, the endocrine aberrations may provide a cause for visceral fat accumulation, probably due to regional differences in steroid-hormone-receptor density. In addition to the increased activity along the adrenocorticosteroid axis, there also seem to be signs of increased activity from the central sympathetic nervous system. These are the established endocrine consequences of hypothalamic arousal in the defeat and defense reactions. There is some evidence that suggests an increased prevalence of psychosocial stress factors is associated with visceral distribution of body fat. Therefore, it is hypothesized that such factors might provide a background not only to a defense reaction and primary hypertension, suggested previously, but also to a defeat reaction, which contributes to an endocrine aberration

  17. C30F12.4 influences oogenesis, fat metabolism, and lifespan in C. elegans.

    Science.gov (United States)

    Wang, Lu; Xu, Fei; Wang, Guishuan; Wang, Xiaorong; Liang, Ajuan; Huang, Hefeng; Sun, Fei

    2016-10-01

    Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.

  18. Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy.

    Science.gov (United States)

    Pingel, Jessica; Petersen, M Christine H; Fredberg, Ulrich; Kjær, Søren G; Quistorff, Bjørn; Langberg, Henning; Hansen, Jacob B

    2015-01-01

    Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager's fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between Kager's fat pad and its surrounding structures during movement of the ankle, suggesting that Kager's fat pad may stabilize and protect the mechanical function of the ankle joint. The aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression of inflammatory markers and metabolic enzymes in Kager's fat pad. A biopsy was taken from Kager's fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation and lipid metabolism. Expression of the majority of analyzed inflammatory marker genes was increased in patients with Achilles tendinopathy compared to that in healthy controls. Expression patterns of the patient group were consistent with reduced lipolysis and increased fatty acid β-oxidation. In the fat pad, the pain-signaling neuropeptide substance P was found to be present in one third of the subjects in the Achilles tendinopathy group but in none of the healthy controls. Gene expression changes in Achilles tendinopathy patient samples were consistent with Kager's fat pad being more inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager's fat pad of Achilles tendinopathy patients.

  19. Diet high in fat and sucrose induces rapid onset of obesity-related metabolic syndrome partly through rapid response of genes involved in lipogenesis, insulin signalling and inflammation in mice

    Directory of Open Access Journals (Sweden)

    Yang Zhi-Hong

    2012-07-01

    Full Text Available Abstract Background Frequent consumption of a diet high in fat and sucrose contributes to lifestyle-related diseases. However, limited information is available regarding the short-term effects of such a diet on the onset of obesity-associated metabolic abnormalities. Methods Male C57BL/6 J mice were divided into two groups and fed a standard chow diet (control group or a high fat–high sucrose diet containing 21% fat and 34% sucrose (HF–HS diet group for 2 or 4 weeks. Results The HF–HS diet significantly induced body weight gain beginning at week 1 and similarly increased mesenteric white adipose tissue weight and plasma insulin levels at weeks 2 and 4. Plasma resistin levels were notably elevated after feeding with the HF–HS diet for 4 weeks. Measurement of hepatic triglycerides and Oil Red O staining clearly indicated increased hepatic lipid accumulation in response to the HF–HS diet as early as 2 weeks. Quantitative PCR analysis of liver and white adipose tissue indicated that, starting at week 2, the HF–HS diet upregulated mRNA expression from genes involved in lipid metabolism and inflammation and downregulated genes involved in insulin signalling. Although plasma cholesterol levels were also rapidly increased by the HF–HS diet, no differences were found between the control and HF–HS diet–fed animals in the expression of key genes involved in cholesterol biosynthesis. Conclusions Our study demonstrates that the rapid onset of hepatosteatosis, adipose tissue hypertrophy and hyperinsulinemia by ingestion of a diet high in fat and sucrose may possibly be due to the rapid response of lipogenic, insulin signalling and inflammatory genes.

  20. Isocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat deposition

    KAUST Repository

    Diaz Rua, Ruben

    2016-03-22

    Background/Objectives: Consumption of fat-rich foods is associated with obesity and related alterations. However, there is a group of individuals, the metabolically obese normal-weight (MONW) subjects, who present normal body weight but have metabolic features characteristic of the obese status, including fat deposition in critical tissues such as liver, recognized as a major cause for the promotion of metabolic diseases. Our aim was to better understand metabolic alterations present in liver of MONW rats applying whole genome transcriptome analysis. Methods: Wistar rats were chronically fed a high-fat diet isocaloric relative to Control animals to avoid the hyperphagia and overweight and to mimic MONW features. Liver transcriptome analysis of both groups was performed. Results: Sustained intake of an isocaloric high-fat diet had a deep impact on the liver transcriptome, mainly affecting lipid metabolism. Although serum cholesterol levels were not affected, circulating triacylglycerols were lower, and metabolic adaptations at gene expression level indicated adaptation toward handling the increased fat content of the diet, an increased triacylglycerol and cholesterol deposition in liver of MONW rats was observed. Moreover, gene expression pointed to increased risk of liver injury. One of the top upregulated genes in this tissue was Krt23, a marker of hepatic disease in humans that was also increased at the protein level.Conclusion:Long-term intake of a high-fat diet, even in the absence of overweight/obesity or increase in classical blood risk biomarkers, promotes a molecular environment leading to hepatic lipid accumulation and increasing the risk of suffering from hepatic diseases.

  1. Fat metabolism during exercise: mechanisms of regulation

    Directory of Open Access Journals (Sweden)

    Monique da Silva Gevaerd

    2006-12-01

    Full Text Available Fats are important energetic fuel to exercise. However, the regulation of fat uptake during exercise is unclear. The main objective of this review was to focus on physiological control mechanisms of mobilization, transport and fat uptake during exercise. The articles of fat metabolism were searched in Pubmed and Lilacs indexes. Classical and current papers were preferred. Evidence suggests that transport of fatty acids (FA from extracellular to intracellular spaces could be the main factor to limit fatty acid uptake. Future studies on fat uptake during exercise can focus on this mechanism. In intense exercise, the lower blood fl ow in the adipose tissue and higher fatty acid reesterifi cation rate impairs fat uptake during exercise. Supplementation of the FA has been used, however, the ideal quantities and forms to prevent gastrointestinal discomfort were not yet determined. In the biological point of view, intramuscular reserve of FA could be more effi cient, because is not necessary to FA to cross the cell membrane. RESUMO Os lipídios são considerados importantes fontes energéticas para a realização de exercícios físicos. Entretanto, os mecanismos de regulação do consumo desse substrato durante o exercício não estão totalmente esclarecidos. O objetivo principal da presente revisão foi abordar mecanismos fisiológicos de controle da mobilização, transporte e utilização de gordura durante o exercício. Os trabalhos indexados no banco de dados Pubmed e Lilacs sobre metabolismo de gordura, foram analisados e os clássicos e recentes foram preferencialmente utilizados. A partir dos dados recentes da literatura, especula-se que o transporte de ácidos graxos do meio extracelular para o meio intracelular pode constituir um dos principais mecanismos limitantes no consumo desse substrato. Estudos sobre o consumo de lipídios durante o exercício devem ser focados sobre esse mecanismo. Em exercício intenso, o menor fl uxo de sangue

  2. Consumption of Walnuts in Combination with Other Whole Foods Produces Physiologic, Metabolic, and Gene Expression Changes in Obese C57BL/6J High-Fat-Fed Male Mice.

    Science.gov (United States)

    Luo, Ting; Miranda-Garcia, Omar; Adamson, Allysa; Hamilton-Reeves, Jill; Sullivan, Debra K; Kinchen, Jason M; Shay, Neil F

    2016-09-01

    Although a reductionist approach has sought to understand the roles of individual nutrients and biochemicals in foods, it has become apparent that there can be differences when studying food components in isolation or within the natural matrix of a whole food. The objective of this study was to determine the ability of whole-food intake to modulate the development of obesity and other metabolic dysfunction in mice fed a high-fat (HF), Western-style obesogenic diet. To test the hypothesis that an n-3 (ω-3) polyunsaturated fatty acid-rich food could synergize with other, largely polyphenol-rich foods by producing greater reductions in metabolic disease conditions, the intake of English walnuts was evaluated in combination with 9 other whole foods. Eight-week-old male C57Bl/6J mice were fed low-fat (LF; 10% fat) and HF control diets, along with an HF diet with 8.6% (wt:wt) added walnuts for 9 wk. The HF control diet contained 46% fat with added sucrose (10.9%, wt:wt) and cholesterol (1%, wt:wt); the added sucrose and cholesterol were not present in the LF diet. Other groups were provided the walnut diet with a second whole food-raspberries, apples, cranberries, tart cherries, broccoli sprouts, olive oil, soy protein, or green tea. All of the energy-containing whole foods were added at an energy level equivalent to 1.5 servings/d. Body weights, food intake, and glucose tolerance were determined. Postmortem, serum lipids and inflammatory markers, hepatic fat, gene expression, and the relative concentrations of 594 biochemicals were measured. The addition of walnuts with either raspberries, apples, or green tea reduced glucose area under the curve compared with the HF diet alone (-93%, -64%, and -54%, respectively, P sprouts or green tea (-49% and -61%, respectively, P < 0.05) had reduced hepatic fat concentrations. There were differences in global gene expression patterns related to whole-food content, with many examples of differences in LF- and HF-fed mice, HF- and

  3. Fat metabolism in formerly obese women

    DEFF Research Database (Denmark)

    Ranneries, C; Bülow, J; Buemann, B

    1998-01-01

    An impaired fat oxidation has been implicated to play a role in the etiology of obesity, but it is unclear to what extent impaired fat mobilization from adipose tissue or oxidation of fat is responsible. The present study aimed to examine fat mobilization from adipose tissue and whole body fat...... intensity. Lipolysis was assessed by glycerol release using microdialysis and blood flow measurement by 133Xe clearance technique. The FO women had lower resting EE than C (3.77 +/- 1.01 vs. 4.88 +/- 0.74 kJ/min, P ... in FO than in C at rest (0.455 +/- 0.299 vs. 0.206 +/- 0.102 mumol.100 g-1.min-1, P fat oxidation rates during rest and recovery were lower in FO than in C (1...

  4. Androgen effect on body composition and fat metabolism.

    Science.gov (United States)

    Jensen, M D

    2000-01-01

    Recognizing the adverse metabolic effects of predominantly visceral body fat distribution associated with low testosterone levels, researchers have investigated the effects of androgen treatment on body fat distribution in men. This presentation reviews the results of research on acute and longer-term effects of treatment with testosterone and dihydrotestosterone. Methods for investigating these results, including measurement of lipoprotein lipase activity and of radiolabeled fat uptake and turnover, are described and discussed.

  5. Quantitative Protein And Fat Metabolism In West African Dwarf ...

    African Journals Online (AJOL)

    Quantitative Protein And Fat Metabolism In West African Dwarf Sheep Fed Margaritaria Discoidea As Supplement. ... Animal Research International ... Protein and energy utilization and quantitative retention of protein, fat and energy was investigated with twelve castrated Djallonke sheep averaging (20.0 ± 2.2kg BW) in ...

  6. Inflammatory and metabolic alterations of Kager's fat pad in chronic achilles tendinopathy

    DEFF Research Database (Denmark)

    Pingel, Jessica; Petersen, Marie Christine Helby; Fredberg, Ulrich

    2015-01-01

    of inflammatory markers and metabolic enzymes in Kager's fat pad. METHODS: A biopsy was taken from Kager's fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation...... inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager's fat pad of Achilles tendinopathy patients.......BACKGROUND: Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager's fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between...

  7. Fat metabolism in formerly obese women

    DEFF Research Database (Denmark)

    Ranneries, C; Bülow, J; Buemann, B

    1998-01-01

    An impaired fat oxidation has been implicated to play a role in the etiology of obesity, but it is unclear to what extent impaired fat mobilization from adipose tissue or oxidation of fat is responsible. The present study aimed to examine fat mobilization from adipose tissue and whole body fat...... oxidation stimulated by exercise in seven formerly obese women (FO) and eight matched controls (C). Lipolysis in the periumbilical subcutaneous adipose tissue, whole body energy expenditure (EE), and substrate oxidation rates were measured before, during, and after a 60-min bicycle exercise bout of moderate...... intensity. Lipolysis was assessed by glycerol release using microdialysis and blood flow measurement by 133Xe clearance technique. The FO women had lower resting EE than C (3.77 +/- 1.01 vs. 4.88 +/- 0.74 kJ/min, P tissue glycerol release was twice as high...

  8. Dietary fats and membrane function: implications for metabolism and disease.

    Science.gov (United States)

    Hulbert, A J; Turner, N; Storlien, L H; Else, P L

    2005-02-01

    Lipids play varied and critical roles in metabolism, with function dramatically modulated by the individual fatty acid moities in complex lipid entities. In particular, the fatty acid composition of membrane lipids greatly influences membrane function. Here we consider the role of dietary fatty acid profile on membrane composition and, in turn, its impact on prevalent disease clusters of the metabolic syndrome and mental illness. Applying the classical physiological conformer-regulator paradigm to quantify the influence of dietary fats on membrane lipid composition (i.e. where the membrane variable is plotted against the same variable in the environment--in this case dietary fats), membrane lipid composition appears as a predominantly regulated parameter. Membranes remain relatively constant in their saturated (SFA) and monounsaturated (MUFA) fatty acid levels over a wide range of dietary variation for these fatty acids. Membrane composition was found to be more responsive to n-6 and n-3 polyunsaturated fatty acid (PUFA) levels in the diet and most sensitive to n-3 PUFA and to the n-3/n-6 ratio. These differential responses are probably due to the fact that both n-6 and n-3 PUFA classes cannot be synthesised de novo by higher animals. Diet-induced modifications in membrane lipid composition are associated with changes in the rates of membrane-linked cellular processes that are major contributors to energy metabolism. For example, in the intrinsic activity of fundamental processes such as the Na+/K+ pump and proton pump-leak cycle. Equally, dietary lipid profile impacts substantially on diseases of the metabolic syndrome with evidence accruing for changes in metabolic rate and neuropeptide regulation (thus influencing both sides of the energy balance equation), in second messenger generation and in gene expression influencing a range of glucose and lipid handling pathways. Finally, there is a growing literature relating changes in dietary fatty acid profile to many

  9. Fat metabolism during exercise in patients with mitochondrial disease

    DEFF Research Database (Denmark)

    Jeppesen, Tina Dysgaard; Orngreen, Mette Cathrine; Van Hall, Gerrit

    2009-01-01

    of palmitate and total free fatty acids, glucose mobilization, and total carbohydrate oxidation. RESULTS: Fat turnover and plasma concentrations of palmitate and total free fatty acids were similar in patients and healthy subjects at rest and during exercise. In line with the higher relative workload......OBJECTIVE: To determine whether patients with defects of the respiratory chain have metabolic adaptations that promote a preferential use of fats or carbohydrates, similar to what is observed in metabolic myopathies affecting glycolysis or fat oxidation. DESIGN: Causation and case-control study...

  10. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism

    Science.gov (United States)

    Yen, Chi-Liang Eric; Nelson, David W.; Yen, Mei-I

    2015-01-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. PMID:25231105

  11. Effects of TiO2 nanoparticles on nutrition metabolism in silkworm fat body

    Directory of Open Access Journals (Sweden)

    J. H. Tian

    2016-06-01

    Full Text Available Silkworm (Bombyx mori is an important economic insect with a fat body that plays a crucial role in the storage and transfer of nutrients. It is also known that TiO2 nanoparticles (NPs can improve feed efficiency and promote silk protein synthesis in the silkworm. In this study, we profiled gene expression in the silkworm fat body after TiO2 NP treatment, validated the major RNA-seq findings, and determined the contents of trehalose and triglyceride, the activity of lipase, and the amount of total proteins. RNA-seq analysis revealed that TiO2 NP treatment caused significant expression changes in 341 genes (P≤0.01, 138 of which were upregulated while the other 203 were downregulated. The expression levels of two target genes in the insulin signaling pathway and two protein metabolism-related target genes, three lipid metabolism-associated target genes, two carbohydrate metabolism related target genes and expression levels of seven heat shock protein genes were increased, and that of threonine dehydratase gene and fatty acid transport protein gene were decreased. The RNA-seq results of 16 genes were validated by quantitative real-time PCR. The lipase activity, content of trehalose, and amount of total proteins were elevated by 3.86-fold, 1.34-fold, and 1.21-fold, respectively, and the content of triglyceride was decreased by 0.94-fold after TiO2 NP treatment. These results indicated that TiO2 NPs activated the insulin signaling pathway, promoted the metabolism of protein, fat, and carbohydrate, and improved nutrition metabolism. Our study provides new support for the understanding of the beneficial effect of TiO2 NPs on silkworm nutrient metabolism.

  12. A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression of insulin signalling and lipid metabolism genes and proteins in male rat offspring: effect of folic acid supplementation.

    Science.gov (United States)

    Cuthbert, Candace E; Foster, Jerome E; Ramdath, D Dan

    2017-10-01

    A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS diet induced higher fasting glucose in offspring v. HFS/F (P=0·027) and down-regulation (Pinsulin resistance v. CON (P=0·030) and HFS/F was associated with higher insulin (P=0·016) and lower glucose (P=0·025). Maternal HFS diet alters offspring insulin sensitivity and de novo hepatic lipogenesis via altered gene and protein expression, which appears to be potentiated by folate supplementation.

  13. Premigratory fat metabolism in hummingbirds: A rumsfeldian approach

    Directory of Open Access Journals (Sweden)

    Raul K. SUAREZ

    2013-06-01

    Full Text Available Hummingbird migration is a remarkable feat, given the small body sizes of migratory species, their high metabolic rates during flight and the long distances traveled using fat to fuel the effort. Equally remarkable is the ability of premigratory hummingbirds in the wild to accumulate fat, synthesized from sugar, at rates as high as 10% of body mass per day. This paper summarizes, using Rumsfeldian terminology, “known knowns” concerning the energetics of hummingbird migration and premigratory fattening. Energy metabolism during hover-feeding on floral nectar is fueled directly by dietary sugar through the pathway recently named the “sugar oxidation cascade”. However, flight without feeding for more than a few minutes requires shifting to fat as a fuel. It is proposed that behavior and metabolic fuel choice are coadapted to maximize the rate of fat deposition during premigratory fattening. The hummingbird liver appears to possess extraordinarily high capacities for fatty acid synthesis. The analysis of “known knowns” leads to identification of “known unknowns”, e.g., the fates of dietary glucose and fructose, the regulation of fat metabolism and metabolic interactions between liver and adipose tissue. The history of science behooves recognition of “unknown unknowns” that, when discovered serendipitously, might shed new light on fundamental mechanisms as well as human pathological conditions [Current Zoology 59 (3: 371–380, 2013].

  14. Adipochemokines induced by ultraviolet irradiation contribute to impaired fat metabolism in subcutaneous fat cells.

    Science.gov (United States)

    Kim, E J; Kim, Y K; Kim, S; Kim, J E; Tian, Y D; Doh, E J; Lee, D H; Chung, J H

    2018-02-01

    Adipose tissue is now appreciated as the pivotal regulator of metabolic and endocrine functions. Subcutaneous (SC) fat, in contrast to visceral fat, may protect against metabolic syndrome and systemic inflammation. We demonstrated that chronic as well as acute ultraviolet (UV) irradiation to the skin induces loss of underlying SC fat. UV-irradiated SC fat may produce chemokines or cytokines that modulate lipid homeostasis and secretion of adipokines. To elucidate UV-induced specific adipochemokines implicated in UV-induced modulation of SC fat. Primary cultured adipocytes were treated with conditioned medium from UV- or sham-irradiated skin cells. Young and older healthy participants provided SC fat from sun-exposed and sun-protected skin. Sun-protected skin from other participants was irradiated with UV. Differentially expressed adipochemokines were screened by cytokine array, and confirmed in vitro and in vivo. The functions of select adipochemokines involved in lipid metabolism were examined via short interfering RNA-mediated knockdown of cognate receptors. Specific adipochemokines, including C-X-C motif chemokine (CXCL) family members such as CXCL5/ENA-78, and C-C motif chemokine (CCL) family members such as CCL20/MIP-3α and CCL5/RANTES, were greatly induced in SC fat by UV exposure. They could impair triglyceride synthesis via downregulation of lipogenic enzymes and sterol regulatory element-binding protein-1 through their respective cognate receptors, CXC chemokine receptor type (CXC-R)2, C-C chemokine receptor type (CCR)-6, and CCR-5. In addition, UV irradiation induced infiltration of adipose tissue macrophages responsible for the secretion of several chemokines into SC fat. These UV-induced adipochemokines may be implicated in the reduction of lipogenesis in SC fat, leading to impairment of fat homeostasis and associated comorbidities such as obesity. © 2017 British Association of Dermatologists.

  15. A pilot investigation of visceral fat adiposity and gene expression profile in peripheral blood cells.

    Science.gov (United States)

    Yamaoka, Masaya; Maeda, Norikazu; Nakamura, Seiji; Kashine, Susumu; Nakagawa, Yasuhiko; Hiuge-Shimizu, Aki; Okita, Kohei; Imagawa, Akihisa; Matsuzawa, Yuji; Matsubara, Ken-ichi; Funahashi, Tohru; Shimomura, Iichiro

    2012-01-01

    Evidence suggests that visceral fat accumulation plays a central role in the development of metabolic syndrome. Excess visceral fat causes local chronic low-grade inflammation and dysregulation of adipocytokines, which contribute in the pathogenesis of the metabolic syndrome. These changes may affect the gene expression in peripheral blood cells. This study for the first time examined the association between visceral fat adiposity and gene expression profile in peripheral blood cells. The gene expression profile was analyzed in peripheral blood cells from 28 obese subjects by microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed using peripheral blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m(2) according to the Japanese criteria, and the estimated visceral fat area (eVFA) was measured by abdominal bioelectrical impedance. Analysis of gene expression profile was carried out with Agilent whole human genome 4 × 44 K oligo-DNA microarray. The expression of several genes related to circadian rhythm, inflammation, and oxidative stress correlated significantly with visceral fat accumulation. Period homolog 1 (PER1) mRNA level in blood cells correlated negatively with visceral fat adiposity. Stepwise multiple regression analysis identified eVFA as a significant determinant of PER1 expression. In conclusion, visceral fat adiposity correlated with the expression of genes related to circadian rhythm and inflammation in peripheral blood cells.

  16. Does caffeine alter muscle carbohydrate and fat metabolism during exercise?

    DEFF Research Database (Denmark)

    Graham, Terry E; Battram, Danielle S; Dela, Flemming

    2008-01-01

    Caffeine, an adenosine receptor antagonist, has been studied for decades as a putative ergogenic aid. In the past 2 decades, the information has overwhelmingly demonstrated that it indeed is a powerful ergogenic aid, and frequently theories have been proposed that this is due to alterations in fat...... and carbohydrate metabolism. While caffeine certainly mobilizes fatty acids from adipose tissue, rarely have measures of the respiratory exchange ratio indicated an increase in fat oxidation. However, this is a difficult measure to perform accurately during exercise, and small changes could be physiologically...... and increased (p caffeine were to increase (p caffeine has ergogenic effects as a result of enhanced fat oxidation...

  17. Fat-soluble micronutrients and metabolic syndrome

    OpenAIRE

    Goncalves, Aurélie; Amiot, Marie-Josèphe

    2017-01-01

    Purpose of review Metabolic syndrome (MetS) is associated with increased risk of obesity, type 2 diabetes mellitus and cardiovascular diseases. MetS prevalence has been associated with diet inadequacy. Conversely, the cumulative incidence of MetS has been inversely associated with a Mediterranean-style diet that includes many different health-beneficial nutrients. Adherence to a Mediterranean-style diet could reduce or at least stabilize metabolic risk factors. Recent findings Low serum level...

  18. C30F12.4 influences oogenesis, fat metabolism, and lifespan in C. elegans

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2016-09-01

    Full Text Available ABSTRACT Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.

  19. Abdominal fat and metabolic risk in obese children and adolescents.

    Science.gov (United States)

    Revenga-Frauca, J; González-Gil, E M; Bueno-Lozano, G; De Miguel-Etayo, P; Velasco-Martínez, P; Rey-López, J P; Bueno-Lozano, O; Moreno, L A

    2009-12-01

    The aim of this study was to investigate fat distribution, mainly abdominal fat, and its relationship with metabolic risk variables in a group of 126 children and adolescents (60 males and 66 females) aged 5.0 to 14.9. According to IOTF criteria, 46 were classified as normal weight, 28 overweight and 52 obese. Weight, height, waist (WC) and hip circumferences were measured. The body mass index (BMI) was calculated. Total body fat, trunkal and abdominal fat were also assessed by dual energy x-ray absorptiometry (DXA). Glucose, insulin, HDL-Cholesterol, triglycerides (TG), ferritine, homocystein and C-reactive protein (CRP) were measured. Obesity status was related with insulin concentrations, CRP, TG and HDL. Obese patients had higher abdominal fat and higher CRP values than overweight and normal subjects. All markers of central body adiposity were related with insulin and lipid metabolism; however, they were not related with homocystein or ferritin. A simple anthropometric measurement, like waist circumference, seems to be a good predictor of the majority of the obesity related metabolic risk variables.

  20. No genetic footprints of the fat mass and obesity associated (FTO) gene in human plasma 1H CPMG NMR metabolic profiles

    DEFF Research Database (Denmark)

    Kjeldahl, Karin; Rasmussen, Morten Arendt; Hasselbalch, Ann Louise

    2014-01-01

    in the plasma samples was investigated at the subject level using supervised multivariate classification in the form of extended canonical variate analysis, classification tree modeling and Lasso (L1) regularized linear logistic regression model (GLMNET). Univariate hypothesis testing of peak intensities...... was used to explore the genotypic effect on the plasma at the population level. The multivariate classification approaches indicated poor discriminative power of the metabolic profiles whereas univariate hypothesis testing provided seven spectral regions with p ..., no reliable markers could be identified, which was confirmed by test set validation. We conclude that it is very unlikely that an FTO-correlated signal can be identified in these 1H CPMG NMR plasma metabolic profiles and speculate that high-throughput un-targeted genotype-metabolic correlations will in many...

  1. Fat distribution, androgens, and metabolism in nonobese women

    NARCIS (Netherlands)

    Seidell, J C; Cigolini, M; Deurenberg, P.; Oosterlee, A.; Doornbos, G

    Eighty-five randomly selected women, all born in 1948, were studied. All were nonobese (body mass index [BMI], 23.3 +/- 0.3 (means +/- SD]). The relationships between three indicators of fat distribution (waist-hip, waist-thigh, and subscapular-triceps ratios) and hormonal and metabolic variables

  2. The dynamics of fat, protein and sugar metabolism during walnut ...

    African Journals Online (AJOL)

    Yomi

    Walnut (Juglans regia L.) is named the “super food” in the 21st century. In this study, the 9-year-old precocious walnut cultivar 'Xiangling' were used to exam the developmental process, and the dynamics of fat, protein and sugar content in the fruit, and the activities of enzymes related with sugar metabolism were further ...

  3. Messenger RNA levels and transcription rates of hepatic lipogenesis genes in genetically lean and fat chickens

    Directory of Open Access Journals (Sweden)

    Douaire Madeleine

    2000-09-01

    Full Text Available Abstract Levels of body fat content in commercial meat chickens have prompted research in order to control the development of this trait. Based on experimentally selected divergent lean and fat lines, many studies have shown that liver metabolism has a major role in the fatness variability. In order to identify which genes are involved in this variability, we investigated the expression of several genes implicated in the hepatic lipid metabolism. The studied genes code for enzymes of fatty acid synthesis [ATP citrate-lyase (ACL, acetyl-CoA carboxylase (ACC, fatty acid synthase (FAS, malic enzyme (ME, stearoyl-CoA desaturase (SCD1], for an apolipoprotein [apolipoprotein A1 (APOA1], and for the CCAAT/enhancer binding protein α (C/EBPα, which is a transcription factor implied in the regulation of several genes of lipid metabolism. The results show that the fat-line chickens display significantly higher hepatic transcription rates and mRNA levels than the lean-line chickens for the ACL, ME and APOA1 genes. This suggests that these genes could be responsible for the phenotypic fatness variability.

  4. Messenger RNA levels and transcription rates of hepatic lipogenesis genes in genetically lean and fat chickens.

    Science.gov (United States)

    Daval, S; Lagarrigue, S; Douaire, M

    2000-01-01

    Levels of body fat content in commercial meat chickens have prompted research in order to control the development of this trait. Based on experimentally selected divergent lean and fat lines, many studies have shown that liver metabolism has a major role in the fatness variability. In order to identify which genes are involved in this variability, we investigated the expression of several genes implicated in the hepatic lipid metabolism. The studied genes code for enzymes of fatty acid synthesis [ATP citrate-lyase (ACL), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), malic enzyme (ME), stearoyl-CoA desaturase (SCD1)], for an apolipoprotein [apolipoprotein A1 (APOA1)], and for the CCAAT/enhancer binding protein alpha (C/EBPalpha), which is a transcription factor implied in the regulation of several genes of lipid metabolism. The results show that the fat-line chickens display significantly higher hepatic transcription rates and mRNA levels than the lean-line chickens for the ACL, ME and APOA1 genes. This suggests that these genes could be responsible for the phenotypic fatness variability.

  5. Fat oxidation at rest predicts peak fat oxidation during exercise and metabolic phenotype in overweight men

    DEFF Research Database (Denmark)

    Rosenkilde, M; Nordby, P; Nielsen, L B

    2010-01-01

    OBJECTIVE: To elucidate if fat oxidation at rest predicts peak fat oxidation during exercise and/or metabolic phenotype in moderately overweight, sedentary men. DESIGN: Cross-sectional study.Subjects:We measured respiratory exchange ratio (RER) at rest in 44 moderately overweight, normotensive...... and normoglycemic men and selected 8 subjects with a low RER (L-RER, body mass index (BMI): 27.9+/-0.9 kg m(-2), RER: 0.76+/-0.02) and 8 with a high RER (H-RER; BMI 28.1+/-1.1 kg m(-2), RER: 0.89+/-0.02). After an overnight fast, a venous blood sample was obtained and a graded exercise test was performed. Fat...... oxidation during exercise was quantified using indirect calorimetry. RESULTS: Peak fat oxidation during exercise was higher in L-RER than in H-RER (0.333+/-0.096 vs 0.169+/-0.028 g min(-1); P

  6. The adverse effect of 4-tert-octylphenol on fat metabolism in pregnant rats via regulation of lipogenic proteins.

    Science.gov (United States)

    Kim, Jun; Kang, Eun-Jin; Park, Mee-Na; Kim, Ji-Eun; Kim, Seung-Chul; Jeung, Eui-Bae; Lee, Geun-Shik; Hwang, Dae-Youn; An, Beum-Soo

    2015-07-01

    Alkylphenols such as 4-tert-octylphenol (OP), nonylphenol, and bisphenol A are classified as endocrine-disrupting chemicals (EDCs). Digestion and metabolism of food are controlled by many endocrine factors, including insulin, glucagon, and estrogen. These factors are differentially regulated during pregnancy. The alteration of nutritional intake and fat metabolism may affect the maintenance of pregnancy and supplementation of nutrients to the fetus, and therefore can cause severe metabolic diseases such as ketosis, marasmus and diabetes mellitus in pregnant individuals. In this study, we examined the effects of OP on fat metabolism in pregnant rats. Ethinyl estradiol (EE) was also administered as an estrogenic positive control. In our results, rats treated with OP showed significantly reduced body weights compared to the control group. In addition, histological analysis showed that the amount of fat deposited in adipocytes was reduced by OP treatment. To study the mechanism of action of OP in fat metabolism, we examined the expression levels of fat metabolism-associated genes in rat adipose tissue and liver by real-time PCR. OP and EE negatively regulated the expression of lipogenic enzymes, including FAS (fatty acid synthase), ACC-1 (acetyl-CoA carboxylase-1), and SCD-1 (stearoyl-CoA desaturase-1). The levels of lipogenic enzyme-associated transcription factors such as C/EBP-α (CAAT enhancer binding protein alpha) and SREBP-1c (sterol regulatory element binding protein-1c) were also reduced in both liver and adipose tissue. In summary, these findings suggest that OP has adverse effects on fat metabolism in pregnant rats and inhibits fat deposition via regulating lipogenic genes in the liver and adipose tissue. The altered fat metabolism by OP may affect the nutrition balance during pregnancy and can cause metabolism-related diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Insulin resistance and postreceptor changes of liver metabolism in fat-fed mice

    DEFF Research Database (Denmark)

    Hedeskov, Carl Jørgen; Capito, Kirsten; Hansen, Svend Erik

    1992-01-01

    Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet......Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet...

  8. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol...

  9. Metabolic abnormalities in young Egyptian women with polycystic ovary syndrome and their relation to ADIPOQ gene variants and body fat phenotype

    Directory of Open Access Journals (Sweden)

    Moushira Zaki

    2015-10-01

    Conclusion: The prevalence of MS was significantly higher in PCOS women than controls, and central obesity and hypertension are risk factors for insulin resistance. Moreover, obesity plays a key role in the development of PCOS and ADIPOQ −11391G>A gene variants showed association with MS.

  10. Common variants near MC4R in relation to body fat, body fat distribution, metabolic traits and energy expenditure

    DEFF Research Database (Denmark)

    Kring, Sofia Inez Iqbal; Holst, C; Toubro, Søren

    2010-01-01

    Common variants near melanocortin receptor 4 (MC4R) have been related to fatness and type 2 diabetes. We examined the associations of rs17782313 and rs17700633 in relation to body fat, body fat distribution, metabolic traits, weight development and energy expenditure....

  11. MiR-183 regulates milk fat metabolism via MST1 in goat mammary epithelial cells.

    Science.gov (United States)

    Chen, Zhi; Shi, HuaiPing; Sun, Shuang; Luo, Jun; Zhang, Wei; Hou, Yu; Loor, Juan J

    2018-03-10

    The nutritional value of goat milk largely depends on its fatty acid content and composition. MicroRNAs (miRNAs) are a class of RNA molecules 18-25nt in length that regulate gene expression and play crucial roles in several biological processes, including fatty acid metabolism. In this study, we analyzed the correlation between differentially expressed miRNAs in goat mammary tissue and the fatty acid composition of goat milk by using Pearson correlations. Results revealed that levels of miR-183 were highly and positively correlated with the fatty acid content in the milk. In addition, we demonstrated that overexpression of miR-183 inhibits milk fat metabolism and inhibition of miR-183 promotes milk fat metabolism. Using Western blot, we demonstrate that MST1, one of the major elements of the Hippo signaling pathway, is a target of miR-183. Immunofluorescence assays revealed that miR-183 targets MST1 in the cytoplasm. In summary, data indicate that miR-183 inhibits the metabolism of milk fat by targeting the MST1 gene in the cytoplasm in goat mammary epithelial cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Effects of high-fat feeding on ectopic fat storage and postprandial lipid metabolism in mouse offspring

    NARCIS (Netherlands)

    Ewijk, Van Petronella A.; Paglialunga, Sabina; Kooi, M.E.; Nunes, Patricia M.; Gemmink, Anne; Slenter, Jos; Kornips, Esther; Jörgensen, Johanna A.; Hoeks, Joris; Wildberger, Joachim E.; Hesselink, Matthijs K.C.; Glatz, Jan F.C.; Heerschap, Arend; Kersten, Sander; Schrauwen, Patrick; Schrauwen-Hinderling, Vera B.

    2015-01-01

    Objective Parental high-fat feeding was proposed to negatively impact metabolic health in offspring. Here, the ectopic fat storage in heart and liver in offspring was investigated, and the effects on mitochondrial function, de novo lipogenesis, and postprandial lipid metabolism were explored in

  13. Effects of high-fat feeding on ectopic fat storage and postprandial lipid metabolism in mouse offspring

    NARCIS (Netherlands)

    Ewijk, P.A. van; Paglialunga, S.; Kooi, M.E.; Nunes, P.M.; Gemmink, A.; Slenter, J.; Kornips, E.; Jorgensen, J.A.; Hoeks, J.; Wildberger, J.E.; Hesselink, M.K.; Glatz, J.F.C.; Heerschap, A.; Kersten, S.; Schrauwen, P.; Schrauwen-Hinderling, V.B.

    2015-01-01

    OBJECTIVE: Parental high-fat feeding was proposed to negatively impact metabolic health in offspring. Here, the ectopic fat storage in heart and liver in offspring was investigated, and the effects on mitochondrial function, de novo lipogenesis, and postprandial lipid metabolism were explored in

  14. Bovine gene polymorphisms related to fat deposition and meat tenderness

    Directory of Open Access Journals (Sweden)

    Marina R.S. Fortes

    2009-01-01

    Full Text Available Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP, thyroglobulin (TG and diacylglycerol O-acyltransferase (DGAT1. A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus, Canchim (5/8 Bos taurus + 3/8 Bos indicus, Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus, Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus.

  15. Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men

    DEFF Research Database (Denmark)

    Brøns, Charlotte; Jensen, Christine B.; Storgaard, Heidi

    2009-01-01

    A high-fat, high-calorie diet is associated with obesity and type 2 diabetes. However, the relative contribution of metabolic defects to the development of hyperglycaemia and type 2 diabetes is controversial. Accumulation of excess fat in muscle and adipose tissue in insulin resistance and type 2...... diabetes may be linked with defective mitochondrial oxidative phosphorylation. The aim of the current study was to investigate acute effects of short-term fat overfeeding on glucose and insulin metabolism in young men. We studied the effects of 5 days' high-fat (60% energy) overfeeding (+50%) versus...... significantly in response to overfeeding. However, peripheral insulin action, muscle mitochondrial function, and general and specific oxidative phosphorylation gene expression were unaffected by high-fat feeding. Insulin secretion increased appropriately to compensate for hepatic, and not for peripheral...

  16. Dietary restriction of mice on a high-fat diet induces substrate efficiency and improves metabolic health.

    Science.gov (United States)

    Duivenvoorde, Loes P M; van Schothorst, Evert M; Bunschoten, Annelies; Keijer, Jaap

    2011-08-01

    High energy intake and, specifically, high dietary fat intake challenge the mammalian metabolism and correlate with many metabolic disorders such as obesity and diabetes. However, dietary restriction (DR) is known to prevent the development of metabolic disorders. The current western diets are highly enriched in fat, and it is as yet unclear whether DR on a certain high-fat (HF) diet elicits similar beneficial effects on health. In this research, we report that HF-DR improves metabolic health of mice compared with mice receiving the same diet on an ad libitum basis (HF-AL). Already after five weeks of restriction, the serum levels of cholesterol and leptin were significantly decreased in HF-DR mice, whereas their glucose sensitivity and serum adiponectin levels were increased. The body weight and measured serum parameters remained stable in the following 7 weeks of restriction, implying metabolic adaptation. To understand the molecular events associated with this adaptation, we analyzed gene expression in white adipose tissue (WAT) with whole genome microarrays. HF-DR strongly influenced gene expression in WAT; in total, 8643 genes were differentially expressed between both groups of mice, with a major role for genes involved in lipid metabolism and mitochondrial functioning. This was confirmed by quantitative real-time reverse transcription-PCR and substantiated by increase in mitochondrial density in WAT of HF-DR mice. These results provide new insights in the metabolic flexibility of dietary restricted animals and suggest the development of substrate efficiency.

  17. Genes involved in bovine milk-fat composition

    NARCIS (Netherlands)

    Schennink, A.

    2009-01-01

    The aim of the research described in this thesis was to identify genes that underlie the genetic variation in bovine milk-fat composition. The fat composition of milk samples from approximately 2,000 Dutch Holstein Friesian cows in their first lactation was measured by gas chromatography.

  18. Individuals with Metabolically Healthy Overweight/Obesity Have Higher Fat Utilization than Metabolically Unhealthy Individuals

    Directory of Open Access Journals (Sweden)

    Arturo Pujia

    2016-01-01

    Full Text Available The mechanisms underlying the change in phenotype from metabolically healthy to metabolically unhealthy obesity are still unclear. The aim of this study is to investigate whether a difference in fasting fat utilization exists between overweight/obese individuals with a favorable cardiovascular risk profile and those with Metabolic Syndrome and Type 2 diabetes. Furthermore, we sought to explore whether there is an association between fasting fat utilization and insulin resistance. In this cross-sectional study, 172 overweight/obese individuals underwent a nutritional assessment. Those with fasting glucose ≥126 mg/dL or antidiabetic treatment were considered to be diabetics. If at least three of the NCEP criteria were present, they had Metabolic Syndrome, while those with less criteria were considered to be healthy overweight/obese. An indirect calorimetry was performed to estimate Respiratory Quotient, an index of nutrient utilization. A lower Respiratory Quotient (i.e., higher fat utilization was found in healthy overweight/obese individuals than in those with Metabolic Syndrome and Type 2 diabetes (0.85 ± 0.05; 0.87 ± 0.06; 0.88 ± 0.05 respectively, p = 0.04. The univariate and multivariable analysis showed a positive association between the Respiratory Quotient and HOMA-IR (slope in statistic (B = 0.004; β = 0.42; p = 0.005; 95% Confidence interval = 0.001–0.006. In this study, we find, for the first time, that the fasting Respiratory Quotient is significantly lower (fat utilization is higher in individuals who are metabolically healthy overweight/obese than in those with metabolically unhealthy obesity. In addition, we demonstrated the association between fat utilization and HOMA-IR, an insulin resistance index.

  19. Impact of visceral fat on gene expression profile in peripheral blood cells in obese Japanese subjects.

    Science.gov (United States)

    Obata, Yoshinari; Maeda, Norikazu; Yamada, Yuya; Yamamoto, Koji; Nakamura, Seiji; Yamaoka, Masaya; Tanaka, Yoshimitsu; Masuda, Shigeki; Nagao, Hirofumi; Fukuda, Shiro; Fujishima, Yuya; Kita, Shunbun; Nishizawa, Hitoshi; Funahashi, Tohru; Matsubara, Ken-Ichi; Matsuzawa, Yuji; Shimomura, Iichiro

    2016-11-29

    Visceral fat plays a central role in the development of metabolic syndrome and atherosclerotic cardiovascular diseases. The association of visceral fat accumulation with cardio-metabolic diseases has been reported, but the impact of visceral fat on the gene expression profile in peripheral blood cells remains to be determined. The aim of this study was to determine the effects of visceral fat area (VFA) and subcutaneous fat area (SFA) on the gene expression profile in peripheral blood cells of obese subjects. All 17 enrolled subjects were hospitalized to receive diet therapy for obesity (defined as body mass index, BMI, greater than 25 kg/m 2 ). VFA and SFA were measured at the umbilical level by computed tomography (CT). Blood samples were subjected to gene expression profile analysis by using SurePrint G3 Human GE Microarray 8 × 60 k ver. 2.0. The correlation between various clinical parameters, including VFA and SFA, and peripheral blood gene expression levels was analyzed. Among the 17 subjects, 12 had normal glucose tolerance or borderline diabetes, and 5 were diagnosed with type 2 diabetes without medications [glycated hemoglobin (HbA1c); 6.3 ± 1.3%]. The mean BMI, VFA, and SFA were 30.0 ± 5.5 kg/m 2 , 177 ± 67 and 245 ± 131 cm 2 , respectively. Interestingly, VFA altered the expression of 1354 genes, including up-regulation of 307 and down-regulation of 1047, under the statistical environment that the parametric false discovery rate (FDR) was less than 0.1. However, no significant effects were noted for SFA or BMI. Gene ontology analysis showed higher prevalence of VFA-associated genes than that of SFA-associated genes, among the genes associated with inflammation, oxidative stress, immune response, lipid metabolism, and glucose metabolism. Accumulation of visceral fat, but not subcutaneous fat, has a significant impact on the gene expression profile in peripheral blood cells in obese Japanese subjects.

  20. The acute effects on duodenal gene expression in healthy men following consumption of a low-fat meal enriched with theobromine or fat.

    Science.gov (United States)

    Smolders, Lotte; Mensink, Ronald P; Boekschoten, Mark V; de Ridder, Rogier J J; Plat, Jogchum

    2018-01-26

    Increasing apoA-I synthesis may improve HDL functionality and lower CVD risk. As theobromine and fat increase fasting apoA-I concentrations, and the intestine is involved in apoA-I production, the acute effects of both were studied on duodenal gene transcription to better understand underlying mechanisms. In this crossover study, 8 healthy men received once a low fat (LF) meal, a LF meal plus theobromine (850 mg), or a high fat (HF) meal. Five hours after meal intake duodenal biopsies were taken for microarray analysis. Theobromine and HF consumption did not change duodenal apoA-I expression. Theobromine did not change gene expression related to lipid and cholesterol metabolism, whereas those related to glycogen/glucose breakdown were downregulated. HF consumption increased gene expression related to lipid and cholesterol uptake and transport, and to glucose storage, while it decreased those related to glucose uptake. Furthermore, genes related to inflammation were upregulated, but inflammation markers in plasma were not changed. In healthy men, acute theobromine and fat consumption did not change duodenal apoA-I mRNA, but inhibited expression of genes related to glucose metabolism. Furthermore, HF intake activated in the duodenum expression of genes related to lipid and cholesterol metabolism and to inflammation.

  1. Dietary fat content and fiber type modulate hind gut microbial community and metabolic markers in the pig.

    Directory of Open Access Journals (Sweden)

    Hui Yan

    Full Text Available Obesity leads to changes in the gut microbial community which contribute to the metabolic dysregulation in obesity. Dietary fat and fiber affect the caloric density of foods. The impact of dietary fat content and fiber type on the microbial community in the hind gut is unknown. Effect of dietary fat level and fiber type on hindgut microbiota and volatile fatty acid (VFA profiles was investigated. Expression of metabolic marker genes in the gut, adipose tissue and liver was determined. A 2 × 2 experiment was conducted in pigs fed at two dietary fat levels (5% or 17.5% swine grease and two fiber types (4% inulin, fermentable fructo-oligosaccharide or 4% solka floc, non-fermentable cellulose. High fat diets (HFD resulted in a higher (P<0.05 total body weight gain, feed efficiency and back fat accumulation than the low fat diet. Feeding of inulin, but not solka floc, attenuated (P<0.05 the HFD-induced higher body weight gain and fat mass accumulation. Inulin feeding tended to lead to higher total VFA production in the cecum and resulted in a higher (P<0.05 expression of acyl coA oxidase (ACO, a marker of peroxisomal β-oxidation. Inulin feeding also resulted in lower expression of sterol regulatory element binding protein 1c (SREBP-1c, a marker of lipid anabolism. Bacteria community structure characterized by DGGE analysis of PCR amplified 16S rRNA gene fragments showed that inulin feeding resulted in greater bacterial population richness than solka floc feeding. Cluster analysis of pairwise Dice similarity comparisons of the DGGE profiles showed grouping by fiber type but not the level of dietary fat. Canonical correspondence analysis (CCA of PCR- DGGE profiles showed that inulin feeding negatively correlated with back fat thickness. This study suggests a strong interplay between dietary fat level and fiber type in determining susceptibility to obesity.

  2. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  3. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ∼40 and ∼1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  4. Effect of testosterone deficiency on cholesterol metabolism in pigs fed a high-fat and high-cholesterol diet

    OpenAIRE

    Cai, Zhaowei; Xi, Haitao; Pan, Yongming; Jiang, Xiaoling; Chen, Liang; Cai, Yueqin; Zhu, Keyan; Chen, Cheng; Xu, Xiaoping; Chen, Minli

    2015-01-01

    Background Testosterone deficiency is associated with increased serum cholesterol levels. However, how testosterone deficiency precisely affects cholesterol metabolism remains unclear. Therefore, in the current study, we examined the effect of testosterone deficiency on cholesterol metabolism and liver gene expression in pigs fed a high-fat and high-cholesterol (HFC) diet. Methods Sexually mature male miniature pigs (6?7 months old) were randomly divided into 3 groups as follows: intact male ...

  5. ACE Reduces Metabolic Abnormalities in a High-Fat Diet Mouse Model

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    Seong-Jong Lee

    2015-01-01

    Full Text Available The medicinal plants Artemisia iwayomogi (A. iwayomogi and Curcuma longa (C. longa radix have been used to treat metabolic abnormalities in traditional Korean medicine and traditional Chinese medicine (TKM and TCM. In this study we evaluated the effect of the water extract of a mixture of A. iwayomogi and C. longa (ACE on high-fat diet-induced metabolic syndrome in a mouse model. Four groups of C57BL/6N male mice (except for the naive group were fed a high-fat diet freely for 10 weeks. Among these, three groups (except the control group were administered a high-fat diet supplemented with ACE (100 or 200 mg/kg or curcumin (50 mg/kg. Body weight, accumulation of adipose tissues in abdomen and size of adipocytes, serum lipid profiles, hepatic steatosis, and oxidative stress markers were analyzed. ACE significantly reduced the body and peritoneal adipose tissue weights, serum lipid profiles (total cholesterol and triglycerides, glucose levels, hepatic lipid accumulation, and oxidative stress markers. ACE normalized lipid synthesis-associated gene expressions (peroxisome proliferator-activated receptor gamma, PPARγ; fatty acid synthase, FAS; sterol regulatory element-binding transcription factor-1c, SREBP-1c; and peroxisome proliferator-activated receptor alpha, PPARα. The results from this study suggest that ACE has the pharmaceutical potential reducing the metabolic abnormalities in an animal model.

  6. 'Fat mass and obesity associated' gene (FTO: No significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents

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    Müller Timo D

    2008-09-01

    Full Text Available Abstract Background We have previously identified strong association of six single nucleotide polymorphisms (SNPs in FTO (fat mass and obesity associated gene to early onset extreme obesity within the first genome wide association study (GWA for this phenotype. The aim of this study was to investigate whether the obesity risk allele of one of these SNPs (rs9939609 is associated with weight loss in a lifestyle intervention program. Additionally, we tested for association of rs9939609 alleles with fasting blood parameters indicative of glucose and lipid metabolism. Methods We initially analysed rs9939609 in a case-control study comprising 519 German overweight and obese children and adolescents and 178 normal weight adults. In 207 of the obese individuals who took part in the outpatient obesity intervention program 'Obeldicks' we further analysed whether carrier status of the obesity risk A-allele of rs9939609 has a differential influence on weight loss after the intervention program. Additionally, we investigated in 480 of the overweight and obese patients whether rs9939609 is associated with fasting blood levels of glucose, triglycerides and HDL and LDL-cholesterol. Genotyping was performed using allele specific polymerase chain reaction (ARMS-PCR. For the association study (case-control approach, the Cochran-Armitage trend test was applied. Blood parameters were analysed using commercially available test kits and the log10-transformed blood parameters and changes in BMI-standard deviation scores (BMI-SDS were analysed by linear regression with sex and age as covariates under an additive mode of inheritance with the rs9939609 A-allele as risk allele. Results We confirmed the association of the risk A-allele of rs9939609 with overweight and early onset obesity (one sided p = 0.036. However, we observed no association of rs9939609 alleles with weight loss or fasting levels of blood glucose, triglycerides and cholesterol. Conclusion We confirmed

  7. Dietary fat content and fiber type modulate hind gut microbial community and metabolic markers in the pig.

    Science.gov (United States)

    Yan, Hui; Potu, Ramesh; Lu, Hang; Vezzoni de Almeida, Vivian; Stewart, Terry; Ragland, Darryl; Armstrong, Arthur; Adeola, Olayiwola; Nakatsu, Cindy H; Ajuwon, Kolapo M

    2013-01-01

    Obesity leads to changes in the gut microbial community which contribute to the metabolic dysregulation in obesity. Dietary fat and fiber affect the caloric density of foods. The impact of dietary fat content and fiber type on the microbial community in the hind gut is unknown. Effect of dietary fat level and fiber type on hindgut microbiota and volatile fatty acid (VFA) profiles was investigated. Expression of metabolic marker genes in the gut, adipose tissue and liver was determined. A 2 × 2 experiment was conducted in pigs fed at two dietary fat levels (5% or 17.5% swine grease) and two fiber types (4% inulin, fermentable fructo-oligosaccharide or 4% solka floc, non-fermentable cellulose). High fat diets (HFD) resulted in a higher (Pfiber type but not the level of dietary fat. Canonical correspondence analysis (CCA) of PCR- DGGE profiles showed that inulin feeding negatively correlated with back fat thickness. This study suggests a strong interplay between dietary fat level and fiber type in determining susceptibility to obesity.

  8. Fatness-Associated FTO Gene Variant Increases Mortality Independent of Fatness - in Cohorts of Danish Men

    DEFF Research Database (Denmark)

    Zimmermann, E; Kring, SI; Berentzen, TL

    2009-01-01

    The A-allele of the single nucleotide polymorphism (SNP), rs9939609, in the FTO gene is associated with increased fatness. We hypothesized that the SNP is associated with morbidity and mortality through the effect on fatness. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 362,200 Danish young...... to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system....

  9. Liver fat percent is associated with metabolic risk factors and the metabolic syndrome in a high-risk vascular cohort

    OpenAIRE

    Hoenig, Michel R; Cowin, Gary; Buckley, Raymond; McHenery, Christine; Coulthard, Alan

    2010-01-01

    Abstract Objective To determine whether liver fat percent (LFP) is associated with the metabolic syndrome independently of visceral fat area (VFA). Methods 43 High-risk vascular patients not on lipid-lowering therapy were evaluated for the Adult Treatment Panel III (ATPIII) metabolic syndrome criteria and underwent magnetic resonance imaging (MRI) to quantify VFA and subcutaneous fat area (SFA) at the L4-L5 disc and liver magnetic resonance spectroscopy (MRS) to quantify LFP. Comparisons: 1. ...

  10. Body fat distribution and inflammation among obese older adults with and without metabolic syndrome

    NARCIS (Netherlands)

    Koster, A.; Stenholm, S.; Alley, D.E.; Kim, L.J.; Simonsick, E.M.; Kanaya, A.M.; Visser, M.; Houston, D.K.; Nicklas, B.J.; Tylavsky, F.A.; Satterfield, S.; Goodpaster, B.H.; Ferrucci, L.; Harris, T.B.

    2010-01-01

    The protective mechanisms by which some obese individuals escape the detrimental metabolic consequences of obesity are not understood. This study examined differences in body fat distribution and adipocytokines in obese older persons with and without metabolic syndrome. Additionally, we examined

  11. Chronic psychological stress and high-fat high-fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice.

    Science.gov (United States)

    de Sousa Rodrigues, Maria Elizabeth; Bekhbat, Mandakh; Houser, Madelyn C; Chang, Jianjun; Walker, Douglas I; Jones, Dean P; Oller do Nascimento, Claudia M P; Barnum, Christopher J; Tansey, Malú G

    2017-01-01

    The mechanisms underlying the association between chronic psychological stress, development of metabolic syndrome (MetS), and behavioral impairment in obesity are poorly understood. The aim of the present study was to assess the effects of mild chronic psychological stress on metabolic, inflammatory, and behavioral profiles in a mouse model of diet-induced obesity. We hypothesized that (1) high-fat high-fructose diet (HFHF) and psychological stress would synergize to mediate the impact of inflammation on the central nervous system in the presence of behavioral dysfunction, and that (2) HFHF and stress interactions would impact insulin and lipid metabolism. C57Bl/6 male mice underwent a combination of HFHF and two weeks of chronic psychological stress. MetS-related conditions were assessed using untargeted plasma metabolomics, and structural and immune changes in the gut and liver were evaluated. Inflammation was measured in plasma, liver, gut, and brain. Our results show a complex interplay of diet and stress on gut alterations, energetic homeostasis, lipid metabolism, and plasma insulin levels. Psychological stress and HFHF diet promoted changes in intestinal tight junctions proteins and increases in insulin resistance and plasma cholesterol, and impacted the RNA expression of inflammatory factors in the hippocampus. Stress promoted an adaptive anti-inflammatory profile in the hippocampus that was abolished by diet treatment. HFHF increased hippocampal and hepatic Lcn2 mRNA expression as well as LCN2 plasma levels. Behavioral changes were associated with HFHF and stress. Collectively, these results suggest that diet and stress as pervasive factors exacerbate MetS-related conditions through an inflammatory mechanism that ultimately can impact behavior. This rodent model may prove useful for identification of possible biomarkers and therapeutic targets to treat metabolic syndrome and mood disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. The response of gene expression associated with lipid metabolism, fat deposition and fatty acid profile in the longissimus dorsi muscle of Gannan yaks to different energy levels of diets.

    Directory of Open Access Journals (Sweden)

    Chao Yang

    Full Text Available The energy available from the diet, which affects fat deposition in vivo, is a major factor in the expression of genes regulating fat deposition in the longissimus dorsi muscle. Providing high-energy diets to yaks might increase intramuscular fat deposition and fatty acid concentrations under a traditional grazing system in cold seasons. A total of fifteen adult castrated male yaks with an initial body weight 274.3 ± 3.14 kg were analyzed for intramuscular adipose deposition and fatty acid composition. The animals were divided into three groups and fed low-energy (LE: 5.5 MJ/kg, medium-energy (ME: 6.2 MJ/kg and high-energy (HE: 6.9 MJ/kg diets, respectively. All animals were fed ad libitum twice daily at 08:00-09:00 am and 17:00-18:00 pm and with free access to water for 74 days, including a 14-d period to adapt to the diets and the environment. Intramuscular fat (IMF content, fatty acid profile and mRNA levels of genes involved in fatty acid synthesis were determined. The energy levels of the diets significantly (P<0.05 affected the content of IMF, total SFA, total MUFA and total PUFA. C16:0, C18:0 and C18:1n9c account for a large proportion of total fatty acids. Relative expression of acetyl-CoA carboxylase (ACACA, fatty acid synthase (FASN, stearoyl-CoA desaturase (SCD, sterol regulatory element-binding protein-1c (SREBP-1c, peroxisome proliferator-activated receptor γ (PPARγ and fatty acid-binding protein 4 (FABP4 was greater in HE than in LE yaks (P<0.05. Moreover, ME yaks had higher (P<0.05 mRNA expression levels of PPARγ, ACACA, FASN, SCD and FABP4 than did the LE yaks. The results demonstrate that the higher energy level of the diets increased IMF deposition and fatty acid content as well as increased intramuscular lipogenic gene expression during the experimental period.

  13. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

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    Nicholas M Morton

    Full Text Available Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L strain.To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney was performed. Known obesity quantitative trait loci (QTL information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity.A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.

  14. Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans

    Science.gov (United States)

    2013-01-01

    Background Animal models are indispensable to understand the lipid metabolism and lipid metabolic diseases. Over the last decade, the nematode Caenorhabditis elegans has become a popular animal model for exploring the regulation of lipid metabolism, obesity, and obese-related diseases. However, the genomic and functional conservation of lipid metabolism from C. elegans to humans remains unknown. In the present study, we systematically analyzed genes involved in lipid metabolism in the C. elegans genome using comparative genomics. Results We built a database containing 471 lipid genes from the C. elegans genome, and then assigned most of lipid genes into 16 different lipid metabolic pathways that were integrated into a network. Over 70% of C. elegans lipid genes have human orthologs, with 237 of 471 C. elegans lipid genes being conserved in humans, mice, rats, and Drosophila, of which 71 genes are specifically related to human metabolic diseases. Moreover, RNA-mediated interference (RNAi) was used to disrupt the expression of 356 of 471 lipid genes with available RNAi clones. We found that 21 genes strongly affect fat storage, development, reproduction, and other visible phenotypes, 6 of which have not previously been implicated in the regulation of fat metabolism and other phenotypes. Conclusions This study provides the first systematic genomic insight into lipid metabolism in C. elegans, supporting the use of C. elegans as an increasingly prominent model in the study of metabolic diseases. PMID:23496871

  15. Integration of transcriptome and whole genomic resequencing data to identify key genes affecting swine fat deposition.

    Directory of Open Access Journals (Sweden)

    Kai Xing

    Full Text Available Fat deposition is highly correlated with the growth, meat quality, reproductive performance and immunity of pigs. Fatty acid synthesis takes place mainly in the adipose tissue of pigs; therefore, in this study, a high-throughput massively parallel sequencing approach was used to generate adipose tissue transcriptomes from two groups of Songliao black pigs that had opposite backfat thickness phenotypes. The total number of paired-end reads produced for each sample was in the range of 39.29-49.36 millions. Approximately 188 genes were differentially expressed in adipose tissue and were enriched for metabolic processes, such as fatty acid biosynthesis, lipid synthesis, metabolism of fatty acids, etinol, caffeine and arachidonic acid and immunity. Additionally, many genetic variations were detected between the two groups through pooled whole-genome resequencing. Integration of transcriptome and whole-genome resequencing data revealed important genomic variations among the differentially expressed genes for fat deposition, for example, the lipogenic genes. Further studies are required to investigate the roles of candidate genes in fat deposition to improve pig breeding programs.

  16. Consumption of Quercetin and Quercetin-Containing Apple and Cherry Extracts Affects Blood Glucose Concentration, Hepatic Metabolism, and Gene Expression Patterns in Obese C57BL/6J High Fat-Fed Mice.

    Science.gov (United States)

    Snyder, Sarah M; Zhao, Bingxin; Luo, Ting; Kaiser, Clive; Cavender, George; Hamilton-Reeves, Jill; Sullivan, Debra K; Shay, Neil F

    2016-05-01

    Intake of polyphenols and polyphenol-rich fruit extracts has been shown to reduce markers of inflammation, diabetes, and hepatic complications that result from the consumption of a high-fat (HF) diet. The objective of this study was to determine whether mice fed polyphenol-rich apple peel extract (AE), cherry extract (CE), and quercetin, a phytochemical abundant in fruits including apples and cherries, would modulate the harmful effects of adiposity on blood glucose regulation, endocrine concentrations, and hepatic metabolism in HF-fed C57BL/6J male mice. Groups of 8-wk-old mice (n = 8 each) were fed 5 diets for 10 wk, including low-fat (LF; 10% of total energy) and HF (60% of total energy) control diets and 3 HF diets containing polyphenol-rich AE, CE, and quercetin (0.2% wt:wt). Also, an in vitro study used HepG2 cells exposed to quercetin (0-100 μmol/L) to determine whether intracellular lipid accumulation could be modulated by this phytochemical. Mice fed the HF control diet consumed 36% more energy, gained 14 g more body weight, and had ∼50% elevated blood glucose concentrations (all P fruit phytochemicals may reduce hepatic lipid accumulation. A quantitative analysis of lipid accumulation in HepG2 cells demonstrated a dose-dependent decrease in lipid content in cells treated with 0-100 μmol quercetin/L (P < 0.05). In mice, consumption of AE, CE, or quercetin appears to modulate some of the harmful effects associated with the consumption of an obesogenic HF diet. Furthermore, in a cell culture model, quercetin was shown to reduce intracellular lipid accumulation in a dose-dependent fashion. © 2016 American Society for Nutrition.

  17. Comparative transcriptome analysis reveals potentially novel roles of Homeobox genes in adipose deposition in fat-tailed sheep.

    Science.gov (United States)

    Kang, Danju; Zhou, Guangxian; Zhou, Shiwei; Zeng, Jie; Wang, Xiaolong; Jiang, Yu; Yang, Yuxin; Chen, Yulin

    2017-11-03

    Adipose tissues are phenotypically, metabolically and functionally heterogeneous based on the sites of their deposition. Undesirable fat deposits in the body are often detrimental to animal and human health. To unravel the potential underlying mechanisms governing accumulation of adipose tissues in various regions of the body, i.e., subcutaneous (SAT), visceral (VAT) and tail (TAT), we profiled transcriptomes from Tan sheep, a Chinese indigenous breed with notable fat tail using RNA-seq. Upon comparison, we identified a total of 1,058 differentially expressed genes (DEGs) between the three adipose types (218, 324, and 795 in SAT/VAT, SAT/TAT, and VAT/TAT, respectively), from which several known key players were identified that are involved in lipid metabolic process, Wnt signals, Vitamin A metabolism, and transcriptional regulation of adipocyte differentiation. We also found that many elevated genes in VAT were notably enriched for key biological processes such as cytokine secretion, signaling molecule interaction and immune systems. Several developmental genes including HOXC11, HOXC12 and HOXC13, and adipose-expressed genes in the tail region, such as HOTAIR_2, HOTAIR_3 and SP9 were specially highlighted, indicating their strong associations with tail fat development in fat-tailed sheep. Our results provide new insight into exploring the specific fat deposition in tail, also contribute to the understanding of differences between adipose depots.

  18. Identifying lipid metabolism genes in pig liver after clenbuterol administration.

    Science.gov (United States)

    Liu, Qiuyue; Zhang, Jin; Guo, Wei; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2012-06-01

    Clenbuterol is a repartition agent (beta 2-adrenoceptor agonist) that can decrease fat deposition and increase skeletal muscle growth at manageable dose. To better understand the molecular mechanism of Clenbuterol's action, GeneChips and real-time PCR were used to compare the gene expression profiles of liver tissue in pigs with/without administration of Clenbuterol. Metabolism effects and the global gene expression profiles of liver tissue from Clenbuterol-treated and untreated pigs were conducted. Function enrichment tests showed that the differentially expressed genes are enriched in glycoprotein protein, plasma membrane, fatty acid and amino acid metabolic process, and cell differentiation and signal transduction groups. Pathway mining analysis revealed that physiological pathways such as MAPK, cell adhesion molecules, and the insulin signaling pathway, were remarkably regulated when Clenbuterol was administered. Gene prioritization algorithm was used to associate a number of important differentially expressed genes with lipid metabolism in response to Clenbuterol. Genes identified as differentially expressed in this study will be candidates for further investigation of the molecular mechanisms involved in Clenbuterol's effects on adipose and skeletal muscle tissue.

  19. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Directory of Open Access Journals (Sweden)

    Amandine Girousse

    Full Text Available When energy is needed, white adipose tissue (WAT provides fatty acids (FAs for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  20. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Science.gov (United States)

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  1. Consumption of a single serving of red raspberries per day reduces metabolic syndrome parameters in high-fat fed mice.

    Science.gov (United States)

    Luo, T; Miranda-Garcia, O; Sasaki, G; Shay, N F

    2017-11-15

    Using an animal model for diet-induced metabolic disease, we have shown previously that the addition of raspberry juice concentrate (RJC) and raspberry puree concentrate (RPC) at a level of 10% of kcal, equivalent to four servings per day, to an obesogenic high-fat, western-style diet (HF) significantly reduced body weight gain, serum resistin levels, and altered the expression of hepatic genes related to lipid metabolism and oxidative stress. This study was designed to examine the effect of a lower level of RJC or RPC consumption, at a level representing a single serving of food per day (2.5% of kcal). For ten weeks, four groups of C57BL/6J mice (n = 8 ea.) were fed: low fat (LF), HF, HF + RJC, or HF + RPC diets. Intake of RJC and RPC decreased final body weight. Hepatic lipid accumulation was significantly decreased in HF + RPC- and HF + RJC-fed mice, compared to HF-fed mice. Further, the relative expression of hepatic genes including Heme oxygenase 1 (Hmox1) and Hormone sensitive lipase (Lipe), were altered by RPC or RJC consumption. In this mouse model of diet-induced metabolic disease, consumption of the equivalent of a single daily serving of either RPC or RJC improved metabolism in mice fed HF diet. We hypothesize that the phytochemicals contained in raspberries, and/or their subsequent metabolites, may be acting to influence gene expression and other regulatory pathways, to produce the metabolic improvements observed in this study.

  2. Body fat distribution in women with familial partial lipodystrophy caused by mutation in the lamin A/C gene

    Directory of Open Access Journals (Sweden)

    Luciana Z Monteiro

    2012-01-01

    Full Text Available Familial partial lipodystrophy (FPLD, Dunnigan variety, is an autosomal dominant disorder caused due to missense mutations in the lamin A/C (LMNA gene encoding nuclear lamina proteins. Patients with FPLD are predisposed to metabolic complications of insulin resistance such as diabetes. We sought to evaluate and compare body fat distribution with dual-emission X-ray absorptiometry in women with and without FPLD and identify densitometric, clinical and metabolic features.

  3. Effects of Chronic Estrogen Administration in the Ventromedial Nucleus of the Hypothalamus (VMH) on Fat and Bone Metabolism in Ovariectomized Rats.

    Science.gov (United States)

    Zhang, Z; Liu, J; Veldhuis-Vlug, A G; Su, Y; Foppen, E; van der Eerden, B C J; Koedam, M; Bravenboer, N; Kalsbeek, A; Boelen, A; Fliers, E; Bisschop, P H

    2016-12-01

    Estrogen deficiency after ovariectomy (OVX) results in increased adiposity and bone loss, which can be prevented by systemic 17-β estradiol (E2) replacement. Studies in transgenic mice suggested that in addition to direct actions of estrogen in peripheral tissues, also estrogen signaling in the hypothalamus regulates fat distribution and bone metabolism. We hypothesized that the protective effect of systemic E2 on fat and bone metabolism in the OVX model is partly mediated through the ventromedial nucleus of the hypothalamus (VMH). To test this hypothesis, we determined the effect of systemic, central, and targeted VMH administration of E2 on fat and bone metabolism in OVX rats. Subcutaneous administration of E2 for 4 weeks decreased body weight, gonadal and perirenal fat, and bone formation rate in OVX rats. This effect was completely mimicked by intracerebroventricular injections of E2, once every 4 days for 4 weeks. Administration of E2 locally in the VMH by retromicrodialysis (3 h) acutely increased expression of the lipolytic gene hormone-sensitive lipase in gonadal and perirenal fat. Finally, chronic administration of E2 in the VMH for 8 weeks decreased perirenal fat but did not affect body weight, trabecular bone volume, or cortical thickness. In conclusion, we demonstrated that intracerebroventricular E2 replacement reduces body weight gain, ameliorates intraabdominal fat accumulation, and reduces bone formation in the OVX rats. E2 administration selectively in the VMH also reduced intraabdominal fat but did not affect bone metabolism.

  4. Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

    International Nuclear Information System (INIS)

    Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun; Yu, Dong Hun; Kim, Hei Jung; Ji, Young Rae; Park, Seo Jin; Park, Si Jun; Kang, Min-Cheol; Jeong, Ja In; Park, Sang-Joon; Lee, Sang Gyu; Lee, Inkyu; Kim, Myoung Ok; Yoon, Duhak; Ryoo, Zae Young

    2014-01-01

    Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes

  5. Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun; Yu, Dong Hun; Kim, Hei Jung; Ji, Young Rae; Park, Seo Jin; Park, Si Jun; Kang, Min-Cheol; Jeong, Ja In [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Park, Sang-Joon [College of Veterinary Medicine, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Sang Gyu [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Inkyu [School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842 (Korea, Republic of); Kim, Myoung Ok [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Yoon, Duhak, E-mail: dhyoon@knu.ac.kr [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Ryoo, Zae Young, E-mail: jaewoong64@hanmail.net [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of)

    2014-02-14

    Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes.

  6. Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism in High Fat Diet-induced Obesity*

    Science.gov (United States)

    Walton, R. Grace; Zhu, Beibei; Unal, Resat; Spencer, Michael; Sunkara, Manjula; Morris, Andrew J.; Charnigo, Richard; Katz, Wendy S.; Daugherty, Alan; Howatt, Deborah A.; Kern, Philip A.; Finlin, Brian S.

    2015-01-01

    Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization of the adipose tissue of the male mice after HFD challenge revealed that the mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ) and a number of PPARγ-regulated genes were higher in the epididymal fat pads of Adipoq-LPL mice than control mice. This included adiponectin, whose mRNA levels were increased, leading to increased adiponectin serum levels in the Adipoq-LPL mice. In many respects, the adipose phenotype of these animals resembles thiazolidinedione treatment except for one important difference, the Adipoq-LPL mice did not gain more fat mass on HFD than control mice and did not have increased expression of genes in adipose such as glycerol kinase, which are induced by high affinity PPAR agonists. Rather, there was selective induction of PPARγ-regulated genes such as adiponectin in the adipose of the Adipoq-LPL mice, suggesting that increasing adipose tissue LPL improves glucose metabolism in diet-induced obesity by improving the adipose tissue phenotype. Adipoq-LPL mice also have increased energy expenditure. PMID:25784555

  7. Dietary enrichment with fish oil prevents high fat-induced metabolic dysfunction in skeletal muscle in mice.

    Directory of Open Access Journals (Sweden)

    Lisa K Philp

    Full Text Available High saturated fat (HF-S diets increase intramyocellular lipid, an effect ameliorated by omega-3 fatty acids in vitro and in vivo, though little is known about sex- and muscle fiber type-specific effects. We compared effects of standard chow, HF-S, and 7.5% HF-S replaced with fish oil (HF-FO diets on the metabolic profile and lipid metabolism gene and protein content in red (soleus and white (extensor digitorum longus muscles of male and female C57BL/6 mice (n = 9-12/group. Weight gain was similar in HF-S- and HF-FO-fed groups. HF-S feeding increased mesenteric fat mass and lipid marker, Oil Red O, in red and mixed muscle; HF-FO increased interscapular brown fat mass. Compared to chow, HF-S and HF-FO increased expression of genes regulating triacylglycerol synthesis and fatty acid transport, HF-S suppressed genes and proteins regulating fatty acid oxidation, whereas HF-FO increased oxidative genes, proteins and enzymes and lipolytic gene content, whilst suppressing lipogenic genes. In comparison to HF-S, HF-FO further increased fat transporters, markers of fatty acid oxidation and mitochondrial content, and reduced lipogenic genes. No diet-by-sex interactions were observed. Neither diet influenced fiber type composition. However, some interactions between muscle type and diet were observed. HF-S induced changes in triacylglycerol synthesis and lipogenic genes in red, but not white, muscle, and mitochondrial biogenesis and oxidative genes were suppressed by HF-S and increased by HF-FO in red muscle only. In conclusion, HF-S feeding promotes lipid storage in red muscle, an effect abrogated by the fish oil, which increases mediators of lipolysis, oxidation and thermogenesis while inhibiting lipogenic genes. Greater storage and synthesis, and lower oxidative genes in red, but not white, muscle likely contribute to lipid accretion encountered in red muscle. Despite several gender-dimorphic genes, both sexes exhibited a similar HF-S-induced metabolic

  8. Dietary Enrichment with Fish Oil Prevents High Fat-Induced Metabolic Dysfunction in Skeletal Muscle in Mice

    Science.gov (United States)

    Philp, Lisa K.; Heilbronn, Leonie K.; Janovska, Alena; Wittert, Gary A.

    2015-01-01

    High saturated fat (HF-S) diets increase intramyocellular lipid, an effect ameliorated by omega-3 fatty acids in vitro and in vivo, though little is known about sex- and muscle fiber type-specific effects. We compared effects of standard chow, HF-S, and 7.5% HF-S replaced with fish oil (HF-FO) diets on the metabolic profile and lipid metabolism gene and protein content in red (soleus) and white (extensor digitorum longus) muscles of male and female C57BL/6 mice (n = 9-12/group). Weight gain was similar in HF-S- and HF-FO-fed groups. HF-S feeding increased mesenteric fat mass and lipid marker, Oil Red O, in red and mixed muscle; HF-FO increased interscapular brown fat mass. Compared to chow, HF-S and HF-FO increased expression of genes regulating triacylglycerol synthesis and fatty acid transport, HF-S suppressed genes and proteins regulating fatty acid oxidation, whereas HF-FO increased oxidative genes, proteins and enzymes and lipolytic gene content, whilst suppressing lipogenic genes. In comparison to HF-S, HF-FO further increased fat transporters, markers of fatty acid oxidation and mitochondrial content, and reduced lipogenic genes. No diet-by-sex interactions were observed. Neither diet influenced fiber type composition. However, some interactions between muscle type and diet were observed. HF-S induced changes in triacylglycerol synthesis and lipogenic genes in red, but not white, muscle, and mitochondrial biogenesis and oxidative genes were suppressed by HF-S and increased by HF-FO in red muscle only. In conclusion, HF-S feeding promotes lipid storage in red muscle, an effect abrogated by the fish oil, which increases mediators of lipolysis, oxidation and thermogenesis while inhibiting lipogenic genes. Greater storage and synthesis, and lower oxidative genes in red, but not white, muscle likely contribute to lipid accretion encountered in red muscle. Despite several gender-dimorphic genes, both sexes exhibited a similar HF-S-induced metabolic and gene

  9. Cocos nucifera water improves metabolic functions in offspring of high fat diet fed Wistar rats.

    Science.gov (United States)

    Kunle-Alabi, Olufadekemi T; Akindele, Opeyemi O; Raji, Yinusa

    2018-03-28

    Maternal high fat diet has been implicated in the aetiology of metabolic diseases in their offspring. The hypolipidaemic actions of Cocos nucifera water improve metabolic indices of dams consuming a high fat diet during gestation. This study investigated the effects of C. nucifera water on metabolism of offspring of dams exposed to high fat diet during gestation. Four groups of pregnant Wistar rat dams (n=6) were treated orally from Gestation Day (GD) 1 to GD 21 as follows: standard rodent feed+10 mL/kg distilled water (Control), standard rodent feed+10 mL/kg C. nucifera water, high fat feed+10 mL/kg distilled water (high fat diet), and high fat feed+10 mL/kg C. nucifera water (high fat diet+C. nucifera water). The feeds were given ad libitum and all dams received standard rodent feed after parturition. Fasting blood glucose was measured in offspring before being euthanized on Postnatal Day (PND) 120. Serum insulin, leptin, lipid profile and liver enzymes were measured. Serum total cholesterol (TC), insulin, alanine transaminase (ALT) and alkaline phosphatase levels were significantly increased (pnucifera water offspring. Results suggest that the adverse effects of maternal high fat diet on offspring's metabolism can be ameliorated by C. nucifera water.

  10. The dynamics of fat, protein and sugar metabolism during walnut ...

    African Journals Online (AJOL)

    The result shows that the developmental process of walnut fruit could be divided into four stages: Slow growth {within 30 days after florescence, (DAF)}, fast growth (30 to 60 DAF), fat accumulation (60 to 100 DAF) and fruit maturity (100 to 140 DAF). Fat content in walnut fruit increased continuously and the maximum ...

  11. Relationship between abdominal fat area measured by screening abdominal fat CT and metabolic syndrome in asymptomatic Korean individuals

    Energy Technology Data Exchange (ETDEWEB)

    Park, Dae Woong; Park, Noh Hyuck; Park, Ji Yeon; Kim, Seon Jeong [Dept. of Radiology, MyoungJi Hospital, Seonam University College of Medicine, Goyang (Korea, Republic of)

    2017-07-15

    The purpose of this study was to investigate the relationship between abdominal fat as assessed by abdominal fat CT and metabolic syndrome (MS), especially in asymptomatic Korean individuals. Retrospectively, a medical record analysis was performed in a total of 111 patients with screening abdominal fat CT. The data such as visceral fat (VF), subcutaneous fat (SF) and VF/SF were elicited by abdominal fat CT, and we analyzed the relationship of VF, SF, and VF/SF with MS and cardiovascular risk factors. In males, VF and SF had a positive correlation with many cardiovascular risk factors and MS, but VF was superior to SF. In females, VF, but not SF, had a positive correlation with some cardiovascular risk factors and MS. The cut-off values of VF and SF to predict MS, which were calculated by drawing receiver operating characteristic curves, were as follows: the cut-off value of VF in men: 136.50 cm{sup 2}, the cut-off value of SF in men: 159.50 cm{sup 2}, and the cut-off value of VF in women: 134.50 cm{sup 2}. In conclusion, VF accumulation was the best predictor of MS and it had a positive correlation with cardiovascular risk factors in both sexes. SF also had a significant association with MS, especially in men, although it was not superior to VF.

  12. Extensive decoupling of metabolic genes in cancer.

    Science.gov (United States)

    Reznik, Ed; Sander, Chris

    2015-05-01

    Tumorigenesis requires the re-organization of metabolism to support malignant proliferation. We examine how the altered metabolism of cancer cells is reflected in the rewiring of co-expression patterns among metabolic genes. Focusing on breast and clear-cell kidney tumors, we report the existence of key metabolic genes which act as hubs of differential co-expression, showing significantly different co-regulation patterns between normal and tumor states. We compare our findings to those from classical differential expression analysis, and counterintuitively observe that the extent of a gene's differential co-expression only weakly correlates with its differential expression, suggesting that the two measures probe different features of metabolism. Focusing on this discrepancy, we use changes in co-expression patterns to highlight the apparent loss of regulation by the transcription factor HNF4A in clear cell renal cell carcinoma, despite no differential expression of HNF4A. Finally, we aggregate the results of differential co-expression analysis into a Pan-Cancer analysis across seven distinct cancer types to identify pairs of metabolic genes which may be recurrently dysregulated. Among our results is a cluster of four genes, all components of the mitochondrial electron transport chain, which show significant loss of co-expression in tumor tissue, pointing to potential mitochondrial dysfunction in these tumor types.

  13. Dietary fat proportionately enhances oxidative stress and glucose intolerance followed by impaired expression of the genes associated with mitochondrial biogenesis.

    Science.gov (United States)

    Das, Nabanita; Mandala, Ashok; Bhattacharjee, Sudarshan; Mukherjee, Debasri; Bandyopadhyay, Debasish; Roy, Sib Sankar

    2017-04-19

    Consumption of food that surpasses the metabolic necessity of the body leads to an epidemic condition termed obesity, which causes several metabolic disorders including oxidative damage. Dietary intervention can enlighten the mechanisms and therapeutics associated with these metabolic disorders. The reported studies related to diet include fat of different kinds and from different sources, however they lack dose response aspects. Our study highlighted the importance of dietary fat modification in modulating oxidative stress-induced glucose intolerance. Animals were maintained on a diet with a varied content of fat (30%/45%/60%) for 12 weeks and the 'withdrawal' group was fed a standard diet for another 10 weeks. The diet containing 60 energy% of fat displayed glucose intolerance, high ALT, low GSH levels and tissue-specific modulation of the prooxidant/antioxidant enzymatic activities in the liver/muscles. Prolonged sustenance of the 60 energy% fat containing diet-fed rats on standard diet led to the alteration of antioxidant activities, reversing the oxidative damage. Notably, the 'withdrawal' group displayed an organ-specific response towards dietary modification where the recovery of the antioxidant activities was observed to be much more pronounced in the liver as compared to the muscle. Further, we identified the differential expression of liver/muscle-specific genes associated with oxidative stress and mitochondrial biogenesis in response to the differing fat content. These genes can serve as markers for HFD-induced metabolic complications involving the liver/muscle. Altogether, our study has highlighted the novel area where obesity-induced oxidative stress linked alterations expressed diet and organ specific responses that are recovered by altering the dietary regimen. Future investigation of dietary modulation will open nascent avenues for developing therapeutic modalities addressing obesity-related metabolic complications.

  14. Lipid metabolic effect of Korean red ginseng extract in mice fed on a high-fat diet.

    Science.gov (United States)

    Song, Yong-Bum; An, Yu Ri; Kim, Seung Jun; Park, Hye-Won; Jung, Jin-Wook; Kyung, Jong-Soo; Hwang, Seung Yong; Kim, Young-Sook

    2012-01-30

    Ginseng saponin and ginsenosides exert anti-obesity effects via the modulation of physiological lipid metabolism in vivo or intracellular signalling in cell culture systems. However, the complicated relationship between the anti-obesity effects of ginseng and gene expression has yet to be defined under in vivo conditions. Therefore, we evaluated the relationship between the anti-obesity effects of Korean red ginseng extract (KRGE) and hepatic gene expression profiles in mice fed long-term on a high-fat diet (HFD) in this study. KRGE reduces the levels of cholesterol, low-density lipoprotein-cholesterol (LDL-C), serum triglycerides, and atherogenic indices. Levels of leptin, adiponectin and insulin, which regulate glucose and lipid metabolism, were impaired profoundly by HFD. However, KRGE treatment brought these levels back to normal. KRGE was found to down-regulate genes associated with lipid metabolism or cholesterol metabolism (Lipa, Cyp7a1, Il1rn, Acot2, Mogat1, Osbpl3, Asah3l, Insig1, Anxa2, Vldlr, Hmgcs1, Sytl4, Plscr4, Pla2g4e, Slc27a3, Enpp6), all of which were up-regulated by HFD. KRGE regulated the expression of genes associated with abnormal physiology via HFD. Leptin, insulin, and adiponectin, which carry out critical functions in energy and lipid metabolism, were shown to be modulated by KRGE. These results show that KRGE is effective in preventing obesity. Copyright © 2011 Society of Chemical Industry.

  15. A Single Nucleotide Polymorphism in the FADS1 Gene is Associated with Plasma Fatty Acid and Lipid Profiles and Might Explain Gender Difference in Body Fat Distribution.

    Science.gov (United States)

    Guo, Huilan; Zhang, Lichao; Zhu, Chaonan; Yang, Fei; Wang, Shanshan; Zhu, Shankuan; Ma, Xiaoguang

    2017-03-31

    Genotyping of the rs174547 polymorphism in the fatty acid desaturase 1 gene (FADS1) shows that it is associated with the FA composition of plasma phospholipids and lipid metabolic indices among several ethnic groups. However, this association requires further confirmation in the Chinese population, and little is known about the effect of polymorphisms in fatty acid-related genes on body fat distribution. Anthropometric measurements of 951 Chinese adults aged 18-79 were obtained and body fat distribution was estimated using dual-energy X-ray absorptiometry. The FA composition of plasma phospholipids was measured by gas chromatography. Multiple linear regression assessed whether the rs174547 genotype was associated with FA composition, body fat distribution, and metabolic traits in additive, dominant, and recessive models. The rs174547 C minor allele was associated with a higher proportion of linoleic acid, lower arachidonic acid and docosahexaenoic acid, as well as lower delta-6-desaturase and delta-5-desaturase activity. Female C allele carriers had lower android fat percentages and lower levels of low-density lipoprotein-cholesterol, while male C allele carriers had lower gynoid fat percentages and higher triglyceride after adjusting for age, income, BMI, behavioral risk factors, and regional fat percentages. An association of FADS1 rs174547 with the FA composition of plasma phospholipids was identified among this Chinese adult population. The association with body fat distribution and lipid metabolic indices differed between men and women, which might explain sexual differences in body fat distribution and lipid metabolism.

  16. Relationship between vaspin gene expression and abdominal fat distribution of Korean women

    International Nuclear Information System (INIS)

    Lee, Jin-A; Park, Hye-Soon; Song, Young-Sook; Jang, Yeon-Jin; Kim, Jong-Hyeok; Lee, Yeon-Ji; Heo, Yoon-Suk

    2011-01-01

    Visceral adipose tissue-derived serpin (vaspin) is a novel adipokine that is thought to have insulin-sensitizing effects. We investigated vaspin mRNA expression in abdominal adipose tissue and examined how gene expression related to abdominal fat distribution and metabolic parameters in Korean women. We measured anthropometric variables, metabolic parameters, serum vaspin concentration, and vaspin mRNA expression in abdominal adipose tissue obtained from women who underwent abdominal gynecological surgery and were aged 18-67 years (n=85). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area were measured in 40 subjects using computed tomography (CT). Vaspin expression was analyzed by real-time quantitative radiotherapy-polymerase chain reaction (RT-PCR) according to abdominal fat distribution. Vaspin mRNA expression was greater in adipocytes than in stroma/vascular cells. In the total subjects, vaspin expression was significantly higher in SAT than in VAT. Vaspin expression in SAT in subcutaneous fat type (VSR ≤0.3) was significantly higher than in visceral fat type (VSR >0.3), although vaspin expression in VAT was similar between subcutaneous and visceral fat type. There was a significant negative correlation between vaspin expression in SAT and VAT area (r=-0.55, p=0.001). Serum vaspin concentration was significantly correlated with fasting insulin (r=0.30, p=0.02), homeostasis model assessment-insulin resistance (HOMA-IR) (r=0.29, p=0.02), and the ratio of vaspin expression in VAT to vaspin expression in SAT (r=0.41, p=0.04). Vaspin expression in abdominal adipose tissue was adipocyte-specific and vaspin expression in SAT decreased as VAT area increased. (author)

  17. Liver fat content in type 2 diabetes: relationship with hepatic perfusion and substrate metabolism

    NARCIS (Netherlands)

    Rijzewijk, Luuk J.; van der Meer, Rutger W.; Lubberink, Mark; Lamb, Hildo J.; Romijn, Johannes A.; de Roos, Albert; Twisk, Jos W.; Heine, Robert J.; Lammertsma, Adriaan A.; Smit, Johannes W. A.; Diamant, Michaela

    2010-01-01

    Hepatic steatosis is common in type 2 diabetes. It is causally linked to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular disease. Experimental data have indicated that increased liver fat may impair hepatic perfusion and metabolism. The aim of the current study was to

  18. Liver fat content in type 2 diabetes: relationship with hepatic perfusion and substrate metabolism

    NARCIS (Netherlands)

    Rijzewijk, L.J.; van der Meer, R.W.; Lubberink, J.M.; Lamb, H.J.; Romijn, J.A.; de Roos, A.; Twisk, J.W.R.; Heine, R.J.; Lammertsma, A.A.; Smit, J.W.A.; Diamant, M.

    2010-01-01

    OBJECTIVE - Hepatic steatosis is common in type 2 diabetes. It is causally linked to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular disease. Experimental data have indicated that increased liver fat may impair hepatic perfusion and metabolism. The aim of the current

  19. Heart disease researchers tailor new theories--now maybe it's genes that make people fat

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, M.F.

    1990-01-05

    Some people who get too big for their britches may be able to blame it on fat genes, according to several reports at the annual meeting of the American Heart Association in New Orleans, La. Two researchers presented studies they say suggest the existence of a genetic basis for obesity, although they have not yet searched for the specific genes, and a third scientist spoke about the structure and metabolic role of the human lipoprotein lipase (LPL) gene. (The molecular biology of the LPL genes has been understood only since 1986.)

  20. Metabolism of fat in subacute combined degeneration of the spinal cord

    Directory of Open Access Journals (Sweden)

    Horacio M. Canelas

    1966-03-01

    Full Text Available In 10 cases of subacute combined degeneration of the spinal cord the absorption, clearance and utilization of labeled fat was studied. In 4 cases disorders of the lipid metabolism were found. Although not significantly, the peripheral and dorsal funiculi syndromes were more severe in the 4 cases with impaired fat metabolism than in the normal cases, while the pyramidal syndrome was almost the same in the two groups. The whole neurological picture was also more severe in the 4 cases with disorders of fat metabolism. These results seem to indicate that the impairment of lipid metabolism evidenced in such cases bears no direct relationship with the demyelinating process in general, and would rather attend a deficiency of metabolites (probably B-complex vitamins other than vitamin B12, which play a more significant role in the preservation of the peripheral nerves.

  1. Sexual dimorphism in obesity-related genes in the epicardial fat during aging.

    Science.gov (United States)

    Kocher, Caitlin; Christiansen, Matthew; Martin, Sarah; Adams, Christopher; Wehner, Paulette; Gress, Todd; Santanam, Nalini

    2017-05-01

    Aging increases the risk of cardiovascular disease and metabolic syndrome. Alterations in epicardial fat play an important pathophysiological role in coronary artery disease and hypertension. We investigated the impact of normal aging on obesity-related genes in epicardial fat. Sex-specific changes in obesity-related genes with aging in epicardial fat (EF) were determined in young (6 months) and old (30/36 months) female and male, Fischer 344 × Brown Norway hybrid (FBN) rats, using a rat obesity RT 2 PCR Array. Circulating sex hormone levels, body and heart weights were determined. Statistical significance was determined using two-tailed Student's t test and Pearson's correlation. Our results revealed sex-specific differences in obesity-related genes with aging. Dramatic changes in the expression profile of obesity-related genes in EF with aging in female, but not in male, FBN rats were observed. The older (30 months) female rats had more significant variations in the abundance of obesity-related genes in the EF compared to that seen in younger female rats or both age groups in male rats. A correlation of changes in obesity-related genes in EF to heart weights was observed in female rats, but not in male rats with aging. No correlation was observed to circulating sex hormone levels. Our findings indicate a dysfunctional EF in female rats with aging compared to male rats. These findings, with further functional validation, might help explain the sex differences in cardiovascular risk and mortality associated with aging observed in humans.

  2. Conjugated Linoleic Acid Supplementation Improves Maternal High Fat Diet-Induced Programming of Metabolic Dysfunction in Adult Male Rat Offspring.

    Science.gov (United States)

    Segovia, Stephanie A; Vickers, Mark H; Gray, Clint; Zhang, Xiaoyuan D; Reynolds, Clare M

    2017-07-27

    The developmental origins of health and disease hypothesis proposes that an adverse early life environment, including in utero exposure to a maternal obesogenic environment, can lead to an increased long-term risk of obesity and related metabolic complications in offspring. We assessed whether maternal supplementation with conjugated linoleic acid (CLA) could prevent some of these adverse effects in offspring exposed to a maternal high fat diet. Sprague-Dawley dams consumed either a: control (CD), control with CLA (CLA), high fat (HF) or high fat with CLA (HFCLA) diet 10 days prior to mating and throughout pregnancy/lactation. Male offspring were weaned onto a standard chow diet. Body composition was quantified by DXA and oral glucose tolerance tests conducted on adult offspring. Gene/protein expression and histological analysis were conducted in adipose tissue. Offspring from HF dams had increased body weight, body fat deposition, impaired insulin sensitivity and adipocyte hypertrophy; all of which were rescued in HFCLA offspring. Molecular and histological analyses of the adipose tissue suggest that disturbances in adipogenesis may mediate the metabolic dysfunction observed in HF offspring. Therefore, CLA supplementation to a maternal obesogenic diet may be a promising strategy to prevent adverse programming outcomes.

  3. Metabolic regulation and the anti-obesity perspectives of human brown fat.

    Science.gov (United States)

    Scheele, Camilla; Nielsen, Søren

    2017-08-01

    Activation of brown adipose tissue (BAT) in adult humans increase glucose and fatty acid clearance as well as resting metabolic rate, whereas a prolonged elevation of BAT activity improves insulin sensitivity. However, substantial reductions in body weight following BAT activation has not yet been shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat. Batokines also seems to be involved in BAT recruitment by stimulating proliferation and differentiation of brown fat progenitors. Increasing human BAT capacity could thus include inducing brown fat biogenesis as well as identifying novel batokines. Another attractive approach would be to induce a brown fat phenotype, the so-called brite or beige fat, within the white fat depots. In adult humans, white fat tissue transformation into beige has been observed in patients with pheochromocytoma, a norepinephrine-producing tumor. Interestingly, human beige fat is predominantly induced in regions that were BAT during early childhood, possibly reflecting that a presence of human beige progenitors is depot specific and originating from BAT. In conclusion, to utilize the anti-obesity potential of human BAT focus should be directed towards identifying novel regulators of brown and beige fat progenitor cells, as well as feedback mechanisms of BAT activation. This would allow for identification of novel anti-obesity targets. Copyright © 2017. Published by Elsevier B.V.

  4. High-fat diet effects on metabolic responses to chronic stress.

    Science.gov (United States)

    Nemati, Marzieh; Zardooz, Homeira; Rostamkhani, Fatemeh; Abadi, Alireza; Foroughi, Forough

    2017-07-01

    High-fat diets and chronic stress are prevalent risk factors for various chronic diseases in modern societies. This study investigated the effect of high-fat diet on glucose-related metabolic responses to chronic foot-shock stress. Male rats were divided into high-fat diet (containing 54.21% saturated and 44.89% unsaturated fatty acids) and normal diet groups and then into stress and non-stress subgroups. The diets were applied for 5 weeks, and stress was induced during the last week of the diet course. Plasma levels of metabolic parameters, HOMA-IR index, intra-abdominal fat weight, and islets' insulin secretion were assessed. High-fat diet increased abdominal fat weight and plasma leptin, and insulin levels in response to stress without affecting HOMA-IR index and islets' insulin secretion. High proportion of unsaturated fat may not lead to deleterious metabolic responses; however combined with chronic stress has a synergistic and adverse effect on visceral adiposity and results in elevated plasma leptin.

  5. Liver fat percent is associated with metabolic risk factors and the metabolic syndrome in a high-risk vascular cohort

    Directory of Open Access Journals (Sweden)

    McHenery Christine

    2010-06-01

    Full Text Available Abstract Objective To determine whether liver fat percent (LFP is associated with the metabolic syndrome independently of visceral fat area (VFA. Methods 43 High-risk vascular patients not on lipid-lowering therapy were evaluated for the Adult Treatment Panel III (ATPIII metabolic syndrome criteria and underwent magnetic resonance imaging (MRI to quantify VFA and subcutaneous fat area (SFA at the L4-L5 disc and liver magnetic resonance spectroscopy (MRS to quantify LFP. Comparisons: 1. Baseline differences in patients with and without the metabolic syndrome 2. Forward binary logistic regression analysis of predictors of the metabolic syndrome with VFA, SFA and LFP as independents 3. Correlates of LFP. Results 43 patients were included in analysis. Patients with metabolic syndrome had greater VFA, SFA and LFP than patients without the metabolic syndrome (all p Conclusions LFP is associated with the metabolic syndrome and renders the current gold standard of VFA redundant in this analysis. This measure of obesity-related cardiovascular risk requires further validation and evaluation in a prospective cohort.

  6. Hepatic gene therapy rescues high-fat diet responses in circadianClockmutant mice.

    Science.gov (United States)

    Meyer-Kovac, Judit; Kolbe, Isa; Ehrhardt, Lea; Leliavski, Alexei; Husse, Jana; Salinas, Gabriela; Lingner, Thomas; Tsang, Anthony H; Barclay, Johanna L; Oster, Henrik

    2017-06-01

    Circadian Clock gene mutant mice show dampened 24-h feeding rhythms and an increased sensitivity to high-fat diet (HFD) feeding. Restricting HFD access to the dark phase counteracts its obesogenic effect in wild-type mice. The extent to which altered feeding rhythms are causative for the obesogenic phenotype of Clock mutant mice, however, remains unknown. Metabolic parameters of wild-type (WT) and Clock Δ19 mutant mice (MT) were investigated under ad libitum and nighttime restricted HFD feeding. Liver circadian clock function was partially rescued by hydrodynamic tail vein delivery of WT- Clock DNA vectors in mutant mice and transcriptional, metabolic, endocrine and behavioral rhythms studied. Nighttime-restricted feeding restored food intake, but not body weight regulation in MT mice under HFD, suggesting Clock -dependent metabolic dysregulation downstream of circadian appetite control. Liver-directed Clock gene therapy partially restored liver circadian oscillator function and transcriptome regulation without affecting centrally controlled circadian behaviors. Under HFD, MT mice with partially restored liver clock function (MT-LR) showed normalized body weight gain, rescued 24-h food intake rhythms, and WT-like energy expenditure. This was associated with decreased nighttime leptin and daytime ghrelin levels, reduced hepatic lipid accumulation, and improved glucose tolerance. Transcriptome analysis revealed that hepatic Clock rescue in MT mice affected a range of metabolic pathways. Liver Clock gene therapy improves resistance against HFD-induced metabolic impairments in mice with circadian clock disruption. Restoring or stabilizing liver clock function might be a promising target for therapeutic interventions in obesity and metabolic disorders.

  7. A Key Gene, PLIN1, Can Affect Porcine Intramuscular Fat Content Based on Transcriptome Analysis

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    Bojiang Li

    2018-04-01

    Full Text Available Intramuscular fat (IMF content is an important indicator for meat quality evaluation. However, the key genes and molecular regulatory mechanisms affecting IMF deposition remain unclear. In the present study, we identified 75 differentially expressed genes (DEGs between the higher (H and lower (L IMF content of pigs using transcriptome analysis, of which 27 were upregulated and 48 were downregulated. Notably, Kyoto Encyclopedia of Genes and Genomes (KEGG enrichment analysis indicated that the DEG perilipin-1 (PLIN1 was significantly enriched in the fat metabolism-related peroxisome proliferator-activated receptor (PPAR signaling pathway. Furthermore, we determined the expression patterns and functional role of porcine PLIN1. Our results indicate that PLIN1 was highly expressed in porcine adipose tissue, and its expression level was significantly higher in the H IMF content group when compared with the L IMF content group, and expression was increased during adipocyte differentiation. Additionally, our results confirm that PLIN1 knockdown decreases the triglyceride (TG level and lipid droplet (LD size in porcine adipocytes. Overall, our data identify novel candidate genes affecting IMF content and provide new insight into PLIN1 in porcine IMF deposition and adipocyte differentiation.

  8. Apolipoprotein gene involved in lipid metabolism

    Science.gov (United States)

    Rubin, Edward; Pennacchio, Len A.

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  9. Maternal High-Fat and High-Salt Diets Have Differential Programming Effects on Metabolism in Adult Male Rat Offspring

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    Stephanie A. Segovia

    2018-03-01

    Full Text Available Maternal high-fat or high-salt diets can independently program adverse cardiometabolic outcomes in offspring. However, there is a paucity of evidence examining their effects in combination on metabolic function in adult offspring. Female Sprague Dawley rats were randomly assigned to either: control (CD; 10% kcal from fat, 1% NaCl, high-salt (SD; 10% kcal from fat, 4% NaCl, high-fat (HF; 45% kcal from fat, 1% NaCl or high-fat and salt (HFSD; 45% kcal from fat, 4% NaCl diets 21 days prior to mating and throughout pregnancy and lactation. Male offspring were weaned onto a standard chow diet and were culled on postnatal day 130 for plasma and tissue collection. Adipocyte histology and adipose tissue, liver, and gut gene expression were examined in adult male offspring. HF offspring had significantly greater body weight, impaired insulin sensitivity and hyperleptinemia compared to CD offspring, but these increases were blunted in HFSD offspring. HF offspring had moderate adipocyte hypertrophy and increased expression of the pre-adipocyte marker Dlk1. There was a significant effect of maternal salt with increased hepatic expression of Dgat1 and Igfb2. Gut expression of inflammatory (Il1r1, Tnfα, Il6, and Il6r and renin–angiotensin system (Agtr1a, Agtr1b markers was significantly reduced in HFSD offspring compared to HF offspring. Therefore, salt mitigates some adverse offspring outcomes associated with a maternal HF diet, which may be mediated by altered adipose tissue morphology and gut inflammatory and renin–angiotensin regulation.

  10. The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism.

    Science.gov (United States)

    Matsuzawa, Yuji; Funahashi, Tohru; Nakamura, Tadashi

    2011-01-01

    Although abdominal obesity or visceral obesity is considered to be one of the components of metabolic syndrome and to have an important role in a cluster of cardiovascular risks, there is no consensus about the definition and diagnostic criteria for this syndrome, probably because there is considerable disagreement about the location and definition of abdominal obesity or visceral obesity.In this review article, the important role of visceral fat accumulation in the development of a variety of lifestyle-related diseases is shown, including cardiovascular disease based on our clinical studies using CT scans, and the mechanism of these disorders is discussed, focusing on adipocytokines, especially adiponectin.The importance of diagnosing metabolic syndrome, in which visceral fat accumulation plays an essential role in the development of multiple risk factors, should be emphasized because lifestyle modification for the reduction of visceral fat may be very effective for the reduction of risks of this type, namely metabolic syndrome in the narrow sense.

  11. Liver metabolism traits in two rabbit lines divergently selected for intramuscular fat.

    Science.gov (United States)

    Martínez-Álvaro, M; Paucar, Y; Satué, K; Blasco, A; Hernández, P

    2017-10-26

    Intramuscular fat (IMF) has a large effect in the sensory properties of meat because it affects tenderness, juiciness and flavour. A divergent selection experiment for IMF in longissimus dorsi (LD) muscle was performed in rabbits. Since liver is the major site of lipogenesis in rabbits, the objective of this work is to study the liver metabolism in the lines of the divergent selection experiment. Intramuscular fat content, perirenal fat weight, liver weight, liver lipogenic activities and plasma metabolites related to liver metabolism were measured in the eighth generation of selection. Direct response on IMF was 0.34 g/100 g of LD, which represented 2.7 SD of the trait, and selection showed a positive correlated response in the perirenal fat weight. High-IMF line showed greater liver size and greater liver lipogenic activities of enzymes glucose-6-phosphate dehydrogenase and malic enzyme. We did not find differences between lines for fatty acid synthase lipogenic activity. With regard to plasma metabolites, low-IMF line showed greater plasma concentration of triglycerides, cholesterol, bilirubin and alkaline phosphatase than high-IMF line, whereas high-IMF line showed greater albumin and alanine transaminase concentrations than low-IMF line. We did not observe differences between lines for glucose, total protein and plasma concentrations. Phenotypic correlations between fat (IMF and perirenal fat weight) and liver traits showed that liver lipogenesis affects fat deposition in both, muscle and carcass. However, the mechanisms whereby liver lipogenesis affected IMF content remain to be clarified.

  12. Metabolic gene polymorphism frequencies in control populations

    DEFF Research Database (Denmark)

    Garte, Seymour; Gaspari, Laura; Alexandrie, Anna-Karin

    2001-01-01

    Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1...

  13. Metabolic gene polymorphism frequencies in control populations.

    NARCIS (Netherlands)

    Garte, S.; Gaspari, L.; Alexandrie, A.K.; Ambrosone, C.; Autrup, H.; Autrup, J.L.; Baranova, H.; Bathum, L.; Benhamou, S.; Boffetta, P.; Bouchardy, C.; Breskvar, K.; Brockmoller, J.; Cascorbi, I.; Clapper, M.L.; Coutelle, C.; Daly, A.; Dell'Omo, M.; Dolzan, V.; Dresler, C.M.; Fryer, A.; Haugen, A.; Hein, D.W.; Hildesheim, A.; Hirvonen, A.; Hsieh, L.L.; Ingelman-Sundberg, M.; Kalina, I.; Kang, D.; Kihara, M.; Kiyohara, C.; Kremers, P.; Lazarus, P.; Marchand, L. le; Lechner, M.C.; Lieshout, E.M.M. van; London, S.; Manni, J.J.; Maugard, C.M.; Morita, S.; Nazar-Stewart, V.; Noda, K.; Oda, Y.; Parl, F.F.; Pastorelli, R.; Persson, I.; Peters, W.H.M.; Rannug, A.; Rebbeck, T.R.; Risch, A.; Roelandt, L.; Romkes, M.; Ryberg, D.; Salagovic, J.; Schoket, B.; Seidegard, J.; Shields, P.G.; Sim, E.; Sinnet, D.; Strange, R.C.; Stucker, I.; Sugimura, H.; To-Figueras, J.; Vineis, P.; Yu, M.C.; Taioli, E.

    2001-01-01

    Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1,

  14. Percentage of Body Fat and Fat Mass Index as a Screening Tool for Metabolic Syndrome Prediction in Colombian University Students

    Science.gov (United States)

    Sanders-Tordecilla, Alejandra; Ojeda-Pardo, Mónica Liliana; Cobo-Mejía, Elisa Andrea; Castellanos-Vega, Rocío del Pilar; Schmidt-RioValle, Jacqueline; González-Ruíz, Katherine

    2017-01-01

    High body fat is related to metabolic syndrome (MetS) in all ethnic groups. Based on the International Diabetes Federation (IDF) definition of MetS, the aim of this study was to explore thresholds of body fat percentage (BF%) and fat mass index (FMI) for the prediction of MetS among Colombian University students. A cross-sectional study was conducted on 1687 volunteers (63.4% women, mean age = 20.6 years). Weight, waist circumference, serum lipids indices, blood pressure, and fasting plasma glucose were measured. Body composition was measured by bioelectrical impedance analysis (BIA) and FMI was calculated. MetS was defined as including more than or equal to three of the metabolic abnormalities according to the IDF definition. Receiver operating curve (ROC) analysis was used to determine optimal cut-off points for BF% and FMI in relation to the area under the curve (AUC), sensitivity, and specificity in both sexes. The overall prevalence of MetS was found to be 7.7%, higher in men than women (11.1% vs. 5.3%; p < 0.001). BF% and FMI were positively correlated to MetS components (p < 0.05). ROC analysis indicated that BF% and FMI can be used with moderate accuracy to identify MetS in university-aged students. BF% and FMI thresholds of 25.55% and 6.97 kg/m2 in men, and 38.95% and 11.86 kg/m2 in women, were found to be indicative of high MetS risk. Based on the IDF criteria, both indexes’ thresholds seem to be good tools to identify university students with unfavorable metabolic profiles. PMID:28902162

  15. Percentage of Body Fat and Fat Mass Index as a Screening Tool for Metabolic Syndrome Prediction in Colombian University Students

    Directory of Open Access Journals (Sweden)

    Robinson Ramírez-Vélez

    2017-09-01

    Full Text Available High body fat is related to metabolic syndrome (MetS in all ethnic groups. Based on the International Diabetes Federation (IDF definition of MetS, the aim of this study was to explore thresholds of body fat percentage (BF% and fat mass index (FMI for the prediction of MetS among Colombian University students. A cross-sectional study was conducted on 1687 volunteers (63.4% women, mean age = 20.6 years. Weight, waist circumference, serum lipids indices, blood pressure, and fasting plasma glucose were measured. Body composition was measured by bioelectrical impedance analysis (BIA and FMI was calculated. MetS was defined as including more than or equal to three of the metabolic abnormalities according to the IDF definition. Receiver operating curve (ROC analysis was used to determine optimal cut-off points for BF% and FMI in relation to the area under the curve (AUC, sensitivity, and specificity in both sexes. The overall prevalence of MetS was found to be 7.7%, higher in men than women (11.1% vs. 5.3%; p < 0.001. BF% and FMI were positively correlated to MetS components (p < 0.05. ROC analysis indicated that BF% and FMI can be used with moderate accuracy to identify MetS in university-aged students. BF% and FMI thresholds of 25.55% and 6.97 kg/m2 in men, and 38.95% and 11.86 kg/m2 in women, were found to be indicative of high MetS risk. Based on the IDF criteria, both indexes’ thresholds seem to be good tools to identify university students with unfavorable metabolic profiles.

  16. Effects of high-fat feeding on ectopic fat storage and postprandial lipid metabolism in mouse offspring.

    Science.gov (United States)

    van Ewijk, Petronella A; Paglialunga, Sabina; Kooi, M Eline; Nunes, Patricia M; Gemmink, Anne; Slenter, Jos; Kornips, Esther; Jörgensen, Johanna A; Hoeks, Joris; Wildberger, Joachim E; Hesselink, Matthijs K C; Glatz, Jan F C; Heerschap, Arend; Kersten, Sander; Schrauwen, Patrick; Schrauwen-Hinderling, Vera B

    2015-11-01

    Parental high-fat feeding was proposed to negatively impact metabolic health in offspring. Here, the ectopic fat storage in heart and liver in offspring was investigated, and the effects on mitochondrial function, de novo lipogenesis, and postprandial lipid metabolism were explored in detail. Male and female mice received either a high-fat (HF) or standard chow (LF) diet during mating, gestation and lactation. All offspring animals received the HF diet. Abdominal visceral adipose tissue tended to be higher in HF/HF mice. Cardiac lipid content was also higher in the HF/HF mice (LF/HF vs. 1.03% ± 0.08% vs. 1.33% ± 0.07% of water signal, P = 0.01). In contrast, hepatic lipid content tended to be lower in HF/HF mice compared to LF/HF mice. A severely disturbed postprandial lipid clearance was revealed in HF/HF mice by the results from the triglyceride (TG) tolerance tests (LF/HF vs. 6,753 ± 2,213 vs. 14,367 ± 1,978 mmol l(-1)  min(-1) , P = 0.01) and (13) C-fatty acid retention test (LF/HF vs. 2.73% ± 0.85% vs. 0.89% ± 0.26% retention from bolus, P = 0.04), which may underlie the lower hepatic lipid content. Here it is shown that HF diet negatively impacts postprandial TG clearance in offspring and results in an overall metabolic unfavorable phenotype and ectopic lipid deposition in the heart and in visceral storage sites. © 2015 The Obesity Society.

  17. Increased susceptibility of post-weaning rats on high-fat diet to metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Hong Sheng Cheng

    2017-11-01

    Full Text Available The present study aimed to examine the effects of the types of high-calorie diets (high-fat and high-fat-high-sucrose diets and two different developmental stages (post-weaning and young adult on the induction of metabolic syndrome. Male, post-weaning and adult (3- and 8-week old, respectively Sprague Dawley rats were given control, high-fat (60% kcal, and high-fat-high-sucrose (60% kcal fat + 30% sucrose water diets for eight weeks (n = 6 to 7 per group. Physical, biochemical, and transcriptional changes as well as liver histology were noted. Post-weaning rats had higher weight gain, abdominal fat mass, fasting glucose, high density lipoprotein cholesterol, faster hypertension onset, but lower circulating advanced glycation end products compared to adult rats. This is accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR α and γ in the liver and receptor for advanced glycation end products (RAGE in the visceral adipose tissue. Post-weaning rats on high-fat diet manifested all phenotypes of metabolic syndrome and increased hepatic steatosis, which are linked to increased hepatic and adipocyte PPARγ expression. Adult rats on high-fat-high-sucrose diet merely became obese and hypertensive within the same treatment duration. Thus, it is more effective and less time-consuming to induce metabolic syndrome in male post-weaning rats with high-fat diet compared to young adult rats. As male rats were selectively included into the study, the results may not be generalisable to all post-weaning rats and further investigation on female rats is required.

  18. Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    So Hun Kim

    2016-01-01

    Full Text Available Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.

  19. High fat diet feeding exaggerates perfluorooctanoic acid-induced liver injury in mice via modulating multiple metabolic pathways.

    Directory of Open Access Journals (Sweden)

    Xiaobing Tan

    Full Text Available High fat diet (HFD is closely linked to a variety of health issues including fatty liver. Exposure to perfluorooctanoic acid (PFOA, a synthetic perfluorinated carboxylic acid, also causes liver injury. The present study investigated the possible interactions between high fat diet and PFOA in induction of liver injury. Mice were pair-fed a high-fat diet (HFD or low fat control with or without PFOA administration at 5 mg/kg/day for 3 weeks. Exposure to PFOA alone caused elevated plasma alanine aminotransferase (ALT and alkaline phosphatase (ALP levels and increased liver weight along with reduced body weight and adipose tissue mass. HFD alone did not cause liver damage, but exaggerated PFOA-induced hepatotoxicity as indicated by higher plasma ALT and AST levels, and more severe pathological changes including hepatocyte hypertrophy, lipid droplet accumulation and necrosis as well as inflammatory cell infiltration. These additive effects of HFD on PFOA-induced hepatotoxicity correlated with metabolic disturbance in liver and blood as well as up-regulation of hepatic proinflammatory cytokine genes. Metabolomic analysis demonstrated that both serum and hepatic metabolite profiles of PFOA, HFD, or HFD-PFOA group were clearly differentiated from that of controls. PFOA affected more hepatic metabolites than HFD, but HFD showed positive interaction with PFOA on fatty acid metabolites including long chain fatty acids and acylcarnitines. Taken together, dietary high fat potentiates PFOA-induced hepatic lipid accumulation, inflammation and necrotic cell death by disturbing hepatic metabolism and inducing inflammation. This study demonstrated, for the first time, that HFD increases the risk of PFOA in induction of hepatotoxicity.

  20. How stable is repression of disallowed genes in pancreatic islets in response to metabolic stress?

    Science.gov (United States)

    Lemaire, Katleen; Granvik, Mikaela; Schraenen, Anica; Goyvaerts, Lotte; Van Lommel, Leentje; Gómez-Ruiz, Ana; In 't Veld, Peter; Gilon, Patrick; Schuit, Frans

    2017-01-01

    The specific phenotype of mature differentiated beta cells not only depends on the specific presence of genes that allow beta cell function but also on the selective absence of housekeeping genes ("disallowed genes") that would interfere with this function. Recent studies have shown that both histone modifications and DNA methylation via the de novo methyltransferase DNMT3A are involved in repression of disallowed genes in neonatal beta cells when these cells acquire their mature phenotype. It is unknown, however, if the environmental influence of advanced age, pregnancy and the metabolic stress of high fat diet or diabetes could alter the repression of disallowed genes in beta cells. In the present study, we show that islet disallowed genes-which are also deeply repressed in FACS-purified beta cells-remain deeply repressed in animals of advanced age and in pregnant females. Moreover, the stability of this repression was correlated with strong and stable histone repression marks that persisted in islets isolated from 2 year old mice and with overall high expression of Dnmt3a in islets. Furthermore, repression of disallowed genes was unaffected by the metabolic stress of high fat diet. However, repression of about half of the disallowed genes was weakened in 16 week-old diabetic db/db mice. In conclusion, we show that the disallowed status of islet genes is stable under physiological challenging conditions (advanced age, pregnancy, high fat diet) but partially lost in islets from diabetic animals.

  1. Mechanisms of TiO2 NPs-induced phoxim metabolism in silkworm (Bombyx mori) fat body.

    Science.gov (United States)

    Hu, J S; Li, F C; Xu, K Z; Ni, M; Wang, B B; Tian, J H; Li, Y Y; Shen, W D; Li, B

    2016-05-01

    Silkworm is an important economic insect. Abuse of organophosphorus pesticides in recent years often leads to poisoning of silkworms, which significantly affects sericulture development by reducing silk production. Previous studies have shown that TiO2 NPs can effectively mitigate the damages caused by organophosphorus pesticides in silk glands and nerve tissues. The fat body is an important metabolic detoxification organ of silkworms, but it is unknown whether TiO2 NPs affect pesticide metabolism in fat body. In this study, we characterized the transcription of antioxidant genes and enzyme activity in fat body after TiO2 NPs and phoxim treatments using transcriptome sequencing, real-time PCR, and enzyme activity assay. Transcriptome sequencing detected 10 720, 10 641, 10 403, and 10 489 genes for control group, TiO2 NPs group, phoxim group, and TiO2 NPs+phoxim group, respectively. The TiO2 NPs+phoxim group had 705 genes with significantly differential expression (FDR<0.001), among which the antioxidant genes thioredoxin reductase 1 and glutathione S-transferase omega 3 were significantly upregulated. In phoxim group, the expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase delta (GSTd), and thioredoxin peroxidase (TPx) were increased by 1.365 -fold, 1.335 -fold, 1.642 -fold, and 1.765 -fold, respectively. The level changes of SOD, CAT, GSTd, and TPx were validated by real time PCR. The contents of reactive oxygen species (ROS), malondialdehyde (MDA), and hydrogen peroxide (H2O2) were increased by 1.598 -fold, 1.946 -fold, and 1.506 -fold, respectively, indicating that TiO2 NPs treatment can relieve phoxim-induced oxidative stress. To clarify the mechanism of TiO2 NPs's effect, the transcription levels of P450 gene family were measured for the TiO2 NPs+phoxim group; the expression levels of CYP4M5, CYP6AB4, CYP6A8, and CYP9G3 were elevated by 2.784 -fold, 3.047 -fold, 2.254 -fold, and 4.253 -fold, respectively, suggesting that

  2. Topographical body fat distribution links to amino acid and lipid metabolism in healthy obese women [corrected].

    Directory of Open Access Journals (Sweden)

    Francois-Pierre J Martin

    Full Text Available Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2 under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

  3. Newborn Body Fat: Associations with Maternal Metabolic State and Placental Size

    OpenAIRE

    Friis, Camilla M.; Qvigstad, Elisabeth; Paasche Roland, Marie Cecilie; Godang, Kristin; Voldner, Nanna; Bollerslev, Jens; Henriksen, Tore

    2013-01-01

    BACKGROUND: Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and pla...

  4. Chlorella Protein Hydrolysate Attenuates Glucose Metabolic Disorder and Fatty Liver in High-fat Diet-induced Obese Mice.

    Science.gov (United States)

    Noguchi, Naoto; Yanagita, Teruyoshi; Rahman, Shaikh Mizanoor; Ando, Yotaro

    2016-07-01

    Chlorella (Parachlorella beijerinckii) powder is reported to show a preventive effect against metabolic syndromes such as arteriosclerosis, hyperlipidemia, and hypertension. Approximately 60% of the chlorella content is protein. In order to understand the role of chlorella protein, we prepared a chlorella protein hydrolysate (CPH) by protease treatment. Male C57BL/6 mice were divided into three groups: a normal diet group, high-fat diet (HFD) group, and high-fat diet supplemented with CPH (HFD+CPH) group. The CPH administration improved glucose intolerance, insulin sensitivity, and adipose tissue hypertrophy in the high-fat diet-fed mice. In addition, the HFD+CPH group had significantly decreased liver total cholesterol and triglyceride levels compared with those in the HFD group. Furthermore, the HFD+CPH group had a decreased level of monocyte chemotactic protein-1 (MCP-1) in serum and a lower MCP-1 mRNA expression level in adipose tissue compared with the HFD group. The present study suggests that chlorella protein hydrolysate can prevent a high-fat diet-induced glucose disorder and fatty liver by inhibiting adipocyte hypertrophy and reducing the MCP-1 protein and gene expression.

  5. Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus.

    Science.gov (United States)

    Nguyen, Long The; Saad, Sonia; Tan, Yi; Pollock, Carol; Chen, Hui

    2017-07-01

    Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity. © 2017 Society for Endocrinology.

  6. Pleiotropic genes for metabolic syndrome and inflammation

    DEFF Research Database (Denmark)

    Kraja, Aldi T; Chasman, Daniel I; North, Kari E

    2014-01-01

    Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors...... metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait...... and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664...

  7. Impact of dietary fat type within the context of altered cholesterol homeostasis on cholesterol and lipoprotein metabolism in the F1B hamster.

    Science.gov (United States)

    Lecker, Jaime L; Matthan, Nirupa R; Billheimer, Jeffrey T; Rader, Daniel J; Lichtenstein, Alice H

    2010-10-01

    Cholesterol status and dietary fat alter several metabolic pathways reflected in lipoprotein profiles. To assess plasma lipoprotein response and mechanisms by which cholesterol and dietary fat type regulate expression of genes involved in lipoprotein metabolism, we developed an experimental model system using F1B hamsters fed diets (12 weeks) enriched in 10% (wt/wt) coconut, olive, or safflower oil with either high cholesterol (0.1%; cholesterol supplemented) or low cholesterol coupled with cholesterol-lowering drugs 10 days before killing (0.01% cholesterol, 0.15% lovastatin, 2% cholestyramine; cholesterol depleted). Irrespective of dietary fat, cholesterol depletion, relative to supplementation, resulted in lower plasma non-high-density lipoprotein (non-HDL) and HDL cholesterol, and triglyceride concentrations (all Ps cholesterol status, coconut oil, relative to olive and safflower oils, resulted in higher non-HDL cholesterol and triglyceride concentrations (both Ps cholesterol depletion are associated with changes in the expression of genes involved in cholesterol metabolism, whereas the effect of dietary fat type on gene expression was modest, which limits the usefulness of the experimental animal model. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Dietary cholesterol and fats at a young age : do they influence cholesterol metabolism in adult life?

    NARCIS (Netherlands)

    Temmerman, A.M.; Vonk, R.J.; Niezen-Koning, K.; Berger, R.; Fernandes, J.

    1989-01-01

    The effects of dietary cholesterol and fats on cholesterol metabolism later in life were studied in Mongolian gerbils. Three groups were given a basic diet with soybean oil, palm kernel oil amounting to 8.75% (w/w), or the basic diet only. In three other groups, cholesterol (0.05%) was added to the

  9. Characterization and mechanisms of lipid metabolism in high-fat diet ...

    African Journals Online (AJOL)

    Characterization and mechanisms of lipid metabolism in high-fat diet induced hyperlipidemia in Mongolian gerbil (Meriones unguiculatus). Hua-Zong Ying, Chen-huan Yu, Zhi-yuan Wang, Bing Yu, Jia-Na Zang, Yue-huan Liu ...

  10. The effect of body fat on basal metabolic rate in adult harp seals (Phoca groenlandica).

    Science.gov (United States)

    Aarseth, J J; Nordøy, E S; Blix, A S

    1999-09-01

    Three adult harp seals (Phoca groenlandica) were fed different daily amounts of capelin (Mallotus villosus), and their body composition determined by use of the tritiated water method at different levels of fattening. Basal metabolic rate (BMR) was measured after 5 days of fasting by indirect calorimetry, and was on average 1.1 W.kg-1 when 45% of body mass (BM) was fat and 2.3 W.kg-1 when body fat was reduced to 13% of BM. This suggests that body fat contributes little to BMR in these animals. It follows, that predictions of BMR on the basis of BM is questionable in seals, in which body fat may change seasonally between 20 and 60% of BM.

  11. Newborn body fat: associations with maternal metabolic state and placental size.

    Directory of Open Access Journals (Sweden)

    Camilla M Friis

    Full Text Available BACKGROUND: Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and placental weight. METHODS: The present work was performed in a subcohort (n = 207 of the STORK study, an observational, prospective study on the determinants of fetal growth and birthweight in healthy pregnancies at Oslo University Hospital, Norway. Fasting glucose, insulin, triglycerides, free fatty acids, HDL- and total cholesterol were measured at week 30-32. Newborn body composition was determined by Dual-Energy X-Ray Absorptiometry (DXA. Placenta was weighed at birth. Linear regression models were used with newborn fat percentage and placental weight as main outcomes. RESULTS: Maternal BMI, fasting glucose and gestational age were independently associated with neonatal fat percentage. However, if placental weight was introduced as a covariate, only placental weight and gestational age remained significant. In the univariate model, the determinants of placenta weight included BMI, insulin, triglycerides, total- and HDL-cholesterol (negatively, gestational weight gain and parity. In the multivariable model, BMI, total cholesterol HDL-cholesterol, gestational weight gain and parity remained independent covariates. CONCLUSION: Maternal BMI and fasting glucose were independently associated with newborn percentage fat. This effect disappeared by introducing placental weight as a covariate. Several metabolic factors associated with maternal BMI were associated with placental weight, but not with neonatal body fat. Our findings are consistent with a concept

  12. Newborn body fat: associations with maternal metabolic state and placental size.

    Science.gov (United States)

    Friis, Camilla M; Qvigstad, Elisabeth; Paasche Roland, Marie Cecilie; Godang, Kristin; Voldner, Nanna; Bollerslev, Jens; Henriksen, Tore

    2013-01-01

    Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and placental weight. The present work was performed in a subcohort (n = 207) of the STORK study, an observational, prospective study on the determinants of fetal growth and birthweight in healthy pregnancies at Oslo University Hospital, Norway. Fasting glucose, insulin, triglycerides, free fatty acids, HDL- and total cholesterol were measured at week 30-32. Newborn body composition was determined by Dual-Energy X-Ray Absorptiometry (DXA). Placenta was weighed at birth. Linear regression models were used with newborn fat percentage and placental weight as main outcomes. Maternal BMI, fasting glucose and gestational age were independently associated with neonatal fat percentage. However, if placental weight was introduced as a covariate, only placental weight and gestational age remained significant. In the univariate model, the determinants of placenta weight included BMI, insulin, triglycerides, total- and HDL-cholesterol (negatively), gestational weight gain and parity. In the multivariable model, BMI, total cholesterol HDL-cholesterol, gestational weight gain and parity remained independent covariates. Maternal BMI and fasting glucose were independently associated with newborn percentage fat. This effect disappeared by introducing placental weight as a covariate. Several metabolic factors associated with maternal BMI were associated with placental weight, but not with neonatal body fat. Our findings are consistent with a concept that the effects of maternal BMI and a number of BMI

  13. Urinary F2-Isoprostanes and Metabolic Markers of Fat Oxidation

    Directory of Open Access Journals (Sweden)

    Dora Il’yasova

    2015-01-01

    Full Text Available Metabolomic studies of increased fat oxidation showed increase in circulating acylcarnitines C2, C8, C10, and C12 and decrease in C3, C4, and C5. We hypothesize that urinary F2-isoprostanes reflect intensity of fatty acid oxidation and are associated with circulating C2, C8, C10, and C12 directly and with C3, C4, and C5 inversely. Four urinary F2-isoprostane isomers and serum acylcarnitines are quantified using LC-MS/MS within the Insulin Resistance Atherosclerosis Study nondiabetic cohort (n = 682. Cross-sectional associations between fasting urinary F2-isoprostanes (summarized as a composite index and the selected acylcarnitines are examined using generalized linear models. F2-isoprostane index is associated with C2 and C12 directly and with C5 inversely: the adjusted beta coefficients are 0.109, 0.072, and −0.094, respectively (P < 0.05. For these acylcarnitines and for F2-isoprostanes, the adjusted odds ratios (ORs of incident diabetes are calculated from logistic regression models: the ORs (95% CI are 0.77 (0.60–0.97, 0.79 (0.62–1.01, 1.18 (0.92–1.53, and 0.51 (0.35–0.76 for C2, C12, C5, and F2-isoprostanes, respectively. The direction of the associations between urinary F2-isoprostanes and three acylcarnitines (C2, C5, and C12 supports our hypothesis. The inverse associations of C2 and C12 and with incident diabetes are consistent with the suggested protective role of efficient fat oxidation.

  14. Prenatal Metformin Exposure in Mice Programs the Metabolic Phenotype of the Offspring during a High Fat Diet at Adulthood

    Science.gov (United States)

    Salomäki, Henriikka; Vähätalo, Laura H.; Laurila, Kirsti; Jäppinen, Norma T.; Penttinen, Anna-Maija; Ailanen, Liisa; Ilyasizadeh, Juan; Pesonen, Ullamari; Koulu, Markku

    2013-01-01

    Aims The antidiabetic drug metformin is currently used prior and during pregnancy for polycystic ovary syndrome, as well as during gestational diabetes mellitus. We investigated the effects of prenatal metformin exposure on the metabolic phenotype of the offspring during adulthood in mice. Methods Metformin (300 mg/kg) or vehicle was administered orally to dams on regular diet from the embryonic day E0.5 to E17.5. Gene expression profiles in liver and brain were analysed from 4-day old offspring by microarray. Body weight development and several metabolic parameters of offspring were monitored both during regular diet (RD-phase) and high fat diet (HFD-phase). At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR. Results Metformin exposed fetuses were lighter at E18.5. There was no effect of metformin on the maternal body weight development or food intake. Metformin exposed offspring gained more body weight and mesenteric fat during the HFD-phase. The male offspring also had impaired glucose tolerance and elevated fasting glucose during the HFD-phase. Moreover, the expression of GLUT4 mRNA was down-regulated in epididymal fat in male offspring prenatally exposed to metformin. Based on the microarray and subsequent qRT-PCR analyses, the expression of Insig-1 was changed in the liver of neonatal mice exposed to metformin prenatally. Furthermore, metformin up-regulated the expression of Insig-1 later in development. Gene set enrichment analysis based on preliminary microarray data identified several differentially enriched pathways both in control and metformin exposed mice. Conclusions The present study shows that prenatal metformin exposure causes long-term programming effects on the metabolic phenotype during high fat diet in mice. This should be taken into consideration when using metformin as a therapeutic agent during

  15. Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood.

    Directory of Open Access Journals (Sweden)

    Henriikka Salomäki

    Full Text Available AIMS: The antidiabetic drug metformin is currently used prior and during pregnancy for polycystic ovary syndrome, as well as during gestational diabetes mellitus. We investigated the effects of prenatal metformin exposure on the metabolic phenotype of the offspring during adulthood in mice. METHODS: Metformin (300 mg/kg or vehicle was administered orally to dams on regular diet from the embryonic day E0.5 to E17.5. Gene expression profiles in liver and brain were analysed from 4-day old offspring by microarray. Body weight development and several metabolic parameters of offspring were monitored both during regular diet (RD-phase and high fat diet (HFD-phase. At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR. RESULTS: Metformin exposed fetuses were lighter at E18.5. There was no effect of metformin on the maternal body weight development or food intake. Metformin exposed offspring gained more body weight and mesenteric fat during the HFD-phase. The male offspring also had impaired glucose tolerance and elevated fasting glucose during the HFD-phase. Moreover, the expression of GLUT4 mRNA was down-regulated in epididymal fat in male offspring prenatally exposed to metformin. Based on the microarray and subsequent qRT-PCR analyses, the expression of Insig-1 was changed in the liver of neonatal mice exposed to metformin prenatally. Furthermore, metformin up-regulated the expression of Insig-1 later in development. Gene set enrichment analysis based on preliminary microarray data identified several differentially enriched pathways both in control and metformin exposed mice. CONCLUSIONS: The present study shows that prenatal metformin exposure causes long-term programming effects on the metabolic phenotype during high fat diet in mice. This should be taken into consideration when using metformin as a

  16. Fat and carbohydrate metabolism during exercise in late-onset Pompe disease

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Laforet, Pascal; Madsen, Karen Lindhardt

    2012-01-01

    forearm exercise testing, and peak work capacity was determined. Fat and carbohydrate metabolism during cycle exercise was examined with a combination of indirect calorimetry and stable isotope methodology. Finally, the effects of an IV glucose infusion on heart rate, ratings of perceived exertion......, and work capacity during exercise were determined. We found that peak oxidative capacity was reduced in the patients to 17.6 vs. 38.8 ml kg(-1) min(-1) in healthy subjects (p = 0.002). There were no differences in the rate of appearance and rate of oxidation of palmitate, or total fat and carbohydrate...... examined the metabolic response to exercise in patients with late-onset Pompe disease, in order to determine if a defect in energy metabolism may play a role in the pathogenesis of Pompe disease. We studied six adult patients with Pompe disease and 10 healthy subjects. The participants underwent ischemic...

  17. Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets.

    Science.gov (United States)

    Shin, Sunhye; Ajuwon, Kolapo M

    2018-02-23

    Dietary fatty acids play important roles in the regulation of fat accumulation or metabolic phenotype of adipocytes, either as brown or beige fat. However, a systematic comparison of effects of diets with different composition of 18-C fatty acids on browning/beiging phenotype has not been done. In this study, we compared the effects of different dietary fats, rich in specific 18-carbon fatty acids, on thermogenesis and lipid metabolism. Male C57BL/6 mice were fed a control diet containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean oil (CON) or high-fat diets (HFD) containing 25% kcal from lard and 20% kcal fat from shea butter (stearic acid-rich fat; SHB), olive oil (oleic acid-rich oil; OO), safflower oil (linoleic acid-rich oil; SFO), or soybean oil (mixed oleic, linoleic, and α-linolenic acids; SBO) ad libitum for 12 weeks, with or without a terminal 4-h norepinephrine (NE) treatment. When compared to SHB, feeding OO, SFO, and SBO resulted in lower body weight gain. The OO fed group had the highest thermogenesis level, which resulted in lower body fat accumulation and improved glucose and lipid metabolism. Feeding SFO downregulated expression of lipid oxidation-related genes and upregulated expression of lipogenic genes, perhaps due to its high n-6:n-3 ratio. In general, HFD-feeding downregulated Ucp1 expression in both subcutaneous and epididymal white adipose tissue, and suppressed NE-induced Pgc1a expression in brown adipose tissue. These results suggest that the position of double bonds in dietary fatty acids, as well as the quantity of dietary fat, may have a significant effect on the regulation of oxidative and thermogenic conditions in vivo.

  18. Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets

    Directory of Open Access Journals (Sweden)

    Sunhye Shin

    2018-02-01

    Full Text Available Dietary fatty acids play important roles in the regulation of fat accumulation or metabolic phenotype of adipocytes, either as brown or beige fat. However, a systematic comparison of effects of diets with different composition of 18-C fatty acids on browning/beiging phenotype has not been done. In this study, we compared the effects of different dietary fats, rich in specific 18-carbon fatty acids, on thermogenesis and lipid metabolism. Male C57BL/6 mice were fed a control diet containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean oil (CON or high-fat diets (HFD containing 25% kcal from lard and 20% kcal fat from shea butter (stearic acid-rich fat; SHB, olive oil (oleic acid-rich oil; OO, safflower oil (linoleic acid-rich oil; SFO, or soybean oil (mixed oleic, linoleic, and α-linolenic acids; SBO ad libitum for 12 weeks, with or without a terminal 4-h norepinephrine (NE treatment. When compared to SHB, feeding OO, SFO, and SBO resulted in lower body weight gain. The OO fed group had the highest thermogenesis level, which resulted in lower body fat accumulation and improved glucose and lipid metabolism. Feeding SFO downregulated expression of lipid oxidation-related genes and upregulated expression of lipogenic genes, perhaps due to its high n-6:n-3 ratio. In general, HFD-feeding downregulated Ucp1 expression in both subcutaneous and epididymal white adipose tissue, and suppressed NE-induced Pgc1a expression in brown adipose tissue. These results suggest that the position of double bonds in dietary fatty acids, as well as the quantity of dietary fat, may have a significant effect on the regulation of oxidative and thermogenic conditions in vivo.

  19. Effects of dietary levels and types of fat on performance and mineral metabolism of broiler chicks.

    Science.gov (United States)

    Atteh, J O; Leeson, S; Julian, R J

    1983-12-01

    Two experiments were conducted to investigate the effects of increasing dietary fat level from 0 to 9.0% and sources of supplemental fat (animal-vegetable fat or corn oil) on the performance and mineral metabolism in broiler chicks from day-old to 3 weeks of age. In experiment 1, increasing dietary fat level significantly (P less than .05) increased 3-week body weight and significantly (P less than .01) improved feed efficiency. There was no significant effect of the treatments on bone ash, bone magnesium, phosphorus, manganese, or zinc, although bone calcium content was significantly (P less than .01) reduced with increase in dietary fat level. Plasma minerals were not significantly affected by the diet treatments. In Experiment 2, neither source of fat, dietary calcium, nor vitamin D3 had any significant effect on performance parameters. Calcium and magnesium retention were significantly (P less than .05) reduced by dietary corn oil. Bone ash and magnesium were significantly (P less than .01) reduced when corn oil was the source of dietary fat, and there was a significant interaction between source of fat and dietary calcium level on bone calcium content. Increasing the dietary vitamin D3 from 1600 to 3200 IU/kg significantly (P less than .05) increased bone calcium content. Bone phosphorus, manganese, and zinc content were not significantly affected by the diet treatments. Plasma magnesium, phosphorus, and zinc content were not significantly affected by the diet treatments. It is concluded that increasing dietary fat, although beneficial for growth, was detrimental to calcium retention and bone calcification. Increasing dietary calcium does not seem to alleviate this problem.

  20. Fats for thoughts: An update on brain fatty acid metabolism.

    Science.gov (United States)

    Romano, Adele; Koczwara, Justyna Barbara; Gallelli, Cristina Anna; Vergara, Daniele; Micioni Di Bonaventura, Maria Vittoria; Gaetani, Silvana; Giudetti, Anna Maria

    2017-03-01

    Brain fatty acid (FA) metabolism deserves a close attention not only for its energetic aspects but also because FAs and their metabolites/derivatives are able to influence many neural functions, contributing to brain pathologies or representing potential targets for pharmacological and/or nutritional interventions. Glucose is the preferred energy substrate for the brain, whereas the role of FAs is more marginal. In conditions of decreased glucose supply, ketone bodies, mainly formed by FA oxidation, are the alternative main energy source. Ketogenic diets or medium-chain fatty acid supplementations were shown to produce therapeutic effects in several brain pathologies. Moreover, the positive effects exerted on brain functions by short-chain FAs and the consideration that they can be produced by intestinal flora metabolism contributed to the better understanding of the link between "gut-health" and "brain-health". Finally, attention was paid also to the regulatory role of essential polyunsaturated FAs and their derivatives on brain homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity

    Science.gov (United States)

    Cantó, Carles; Houtkooper, Riekelt H.; Pirinen, Eija; Youn, Dou Y.; Oosterveer, Maaike H.; Cen, Yana; Fernandez-Marcos, Pablo J.; Yamamoto, Hiroyasu; Andreux, Pénélope A.; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A.; Auwerx, Johan

    2013-01-01

    SUMMARY As NAD+ is a rate-limiting co-substrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38 —both NAD+ consumers— increases NAD+ bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD+ precursor with the ability to increase NAD+ levels, Sir2-dependent gene silencing and replicative lifespan in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD+ levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin, NR, could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function. PMID:22682224

  2. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.

    Science.gov (United States)

    Cantó, Carles; Houtkooper, Riekelt H; Pirinen, Eija; Youn, Dou Y; Oosterveer, Maaike H; Cen, Yana; Fernandez-Marcos, Pablo J; Yamamoto, Hiroyasu; Andreux, Pénélope A; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A; Auwerx, Johan

    2012-06-06

    As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+) bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD(+) precursor with the ability to increase NAD(+) levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Mice lacking natural killer T cells are more susceptible to metabolic alterations following high fat diet feeding.

    Directory of Open Access Journals (Sweden)

    Brittany V Martin-Murphy

    Full Text Available Current estimates suggest that over one-third of the adult population has metabolic syndrome and three-fourths of the obese population has non-alcoholic fatty liver disease (NAFLD. Inflammation in metabolic tissues has emerged as a universal feature of obesity and its co-morbidities, including NAFLD. Natural Killer T (NKT cells are a subset of innate immune cells that abundantly reside within the liver and are readily activated by lipid antigens. There is general consensus that NKT cells are pivotal regulators of inflammation; however, disagreement exists as to whether NKT cells exert pathogenic or suppressive functions in obesity. Here we demonstrate that CD1d(-/- mice, which lack NKT cells, were more susceptible to weight gain and fatty liver following high fat diet (HFD feeding. Compared with their WT counterparts, CD1d(-/- mice displayed increased adiposity and greater induction of inflammatory genes in the liver suggestive of the precursors of NAFLD. Calorimetry studies revealed a significant increase in food intake and trends toward decreased metabolic rate and activity in CD1d(-/- mice compared with WT mice. Based on these findings, our results suggest that NKT cells play a regulatory role that helps to prevent diet-induced obesity and metabolic dysfunction and may play an important role in mechanisms governing cross-talk between metabolism and the immune system to regulate energy balance and liver health.

  4. Glucagon-insulin interaction on fat cell metabolism using c14 glucose

    International Nuclear Information System (INIS)

    Zewail, M.A.; Nielsen, J.H.

    1984-01-01

    Glucagon is known to stimulate the lipolysis in isolated fat cells from young rats, but not in fat cells from old heavy rate (Manganiello 1972). Insulin is known to counteract the lipolytic effect and to stimulate the synthesis of fatty acids from glucose. However, little is known about the interaction between the two hormones on the glucose metabolism. Experiments based on the use of various inhibitors of lipolysis have however, clearly shown that glucagon can also stimulate the entry and overall oxidation of glucose by mechanism which is distinct from its lipolysis stimulating mechanism (M. Blecher et al. 1969). Fat cells from old heavy rats are known to be less responsive to both the lipogenic action of insulin and the lipolytic action of glucagon than fat cells from young lean rats (E.G. Hansen, Nielsen and Gliemann, 1974). The aim of the present study was to see how glucagon affects glucose metabolism in fat cells, and whether this effect was dependent on the lipolytic action of glucagon

  5. Tocotrienols Reverse Cardiovascular, Metabolic and Liver Changes in High Carbohydrate, High Fat Diet-Fed Rats

    Directory of Open Access Journals (Sweden)

    Weng-Yew Wong

    2012-10-01

    Full Text Available Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome.

  6. Variations in insulin responsiveness in rat fat cells are due to metabolic differences rather than insulin binding

    DEFF Research Database (Denmark)

    Hansen, Finn Mølgård; Nilsson, Poul; Sonne, Ole

    1983-01-01

    to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism......Insulin resistance was studied by comparing insulin response and insulin binding in four groups of rats. Glucose metabolism in isolated fat cells from male Wistar rats weighing 340 g was less responsive to a supramaximal dose of insulin than glucose metabolism in fat cells from rats weighing 200 g....... Induction of streptozotocin-diabetes in rats weighing 200 g resulted in a marked decrease in the insulin responsiveness of fat cells. Ventromedial hypothalamic lesions of 340 g rats had the opposite effect and restored the insulin responsiveness of fat cells. The responsiveness in the four groups...

  7. Direct association of a promoter polymorphism in the CD36/FAT fatty acid transporter gene with Type 2 diabetes mellitus and insulin resistance

    NARCIS (Netherlands)

    Corpeleijn, E.; Kallen, van der C.J.H.; Kruijshoop, M.; Magagnin, M.G.P.; Bruin, de T.W.A.; Feskens, E.J.M.; Saris, W.H.M.; Blaak, E.E.

    2006-01-01

    AIMS: The membrane-bound fatty acid transporter CD36/FAT may play a role in disturbed fatty acid handling as observed in the metabolic syndrome and Type 2 diabetes mellitus (T2DM). Genetic variation in the CD36 gene may contribute to the aetiology of diabetes. METHODS: A population-based cohort in

  8. Modifications of Western-type diet regarding protein, fat and sucrose levels as modulators of steroid metabolism and activity in liver.

    Science.gov (United States)

    Krawczyńska, Agata; Herman, Andrzej P; Antushevich, Hanna; Bochenek, Joanna; Dziendzikowska, Katarzyna; Gajewska, Alina; Gromadzka-Ostrowska, Joanna

    2017-01-01

    The aim of the study was to evaluate whether the modification of the Western-type diet (high-fat, high-sucrose diet rich in saturated fatty acids) considering macronutrients content would influence hepatic metabolism and activity of steroids. For 3 weeks Wistar rat were fed the Western-type diet (21% fat, 35% sucrose, 19% protein, lard) and its modifications regarding dietary protein (10 and 19%), fat (5 and 21%) and sucrose (0 and 35%) levels. The steroid 5α-reductase type 1 (Srd5a1) and androgen receptor (Ar) gene expression as well as testosterone (T) conversion towards 5α-reduced derivatives in liver were positively correlated with body weight gain. The Western-type diets with decreased protein content regardless of the sucrose level exerted the most negative effect on the antioxidant system decreasing catalase (Cat), sodium dismutase (Sod1) and glutathione peroxidase (Gpx1) gene expression as well as Cat and Gpx activity and total antioxidant status, simultaneously intensifying lipid peroxidation. The impaired antioxidant system was accompanied by decreased level of hepatic T metabolism towards estrogens: 17β-estradiol (E2) and estriol, and increased estrogen receptor type 1 (Esr1) gene expression. Liver Esr1 mRNA level was differently correlated with T (positively) and E2 (negatively) plasma levels. Whereas the fat reduction in Western-type diet restored the plasma proportion between T and E2. In conclusion it could be stated that Western-type diet modification relating to protein, sucrose and fat content can influence hepatic steroid metabolism and activity; however the estrogens and androgens metabolism in liver would be connected with impairment of liver function or catabolic activity, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Cloning and characterization of chicken fat mass and obesity associated (Fto) gene: fasting affects Fto expression.

    Science.gov (United States)

    Tiwari, A; Krzysik-Walker, S M; Ramachandran, R

    2012-01-01

    Fat mass and obesity associated gene (Fto), also known as Fatso, is a member of the Fe-II and 2-oxoglutarate-dependent dioxygenase superfamily. Recent studies in humans and rodents suggest that Fto is involved in food intake regulation and lipid metabolism, whereas single nucleotide mutations in the Fto gene are associated with obesity and type 2 diabetes. The Fto gene is highly conserved from green algae to humans, but little is known about the avian Fto gene or protein. The objectives of the current study were to clone full-length chicken Fto cDNA and to determine the effect of age or feeding status on Fto expression. With the use of rapid amplification of cDNA ends, the full-length chicken Fto cDNA was cloned and found to share 63% to 66% homology with the mammalian Fto nucleotide sequence. Several regions of the chicken Fto protein, including the substrate (2-oxoglutarate) binding domains, were found to be identical to mammalian Fto protein. Western blotting with anti-human Fto antibody and reverse transcription PCR studies showed that Fto protein and gene were ubiquitously expressed in various tissues of the chicken. With the use of quantitative PCR, Fto mRNA levels were found to be higher in liver and skeletal muscle of 8-wk-old chickens than in 4-wk-old chickens. In addition, alterations in feeding status resulted in significant changes in Fto mRNA and Fto protein expression in the liver but not in skeletal muscle and adipose tissue of broiler chickens. Taken together, our data suggest that Fto probably plays a significant role in liver function and energy metabolism in the chicken. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Uncoupling proteins, dietary fat and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Warden Craig H

    2006-09-01

    Full Text Available Abstract There has been intense interest in defining the functions of UCP2 and UCP3 during the nine years since the cloning of these UCP1 homologues. Current data suggest that both UCP2 and UCP3 proteins share some features with UCP1, such as the ability to reduce mitochondrial membrane potential, but they also have distinctly different physiological roles. Human genetic studies consistently demonstrate the effect of UCP2 alleles on type-2 diabetes. Less clear is whether UCP2 alleles influence body weight or body mass index (BMI with many studies showing a positive effect while others do not. There is strong evidence that both UCP2 and UCP3 protect against mitochondrial oxidative damage by reducing the production of reactive oxygen species. The evidence that UCP2 protein is a negative regulator of insulin secretion by pancreatic β-cells is also strong: increased UCP2 decreases glucose stimulated insulin secretion ultimately leading to β-cell dysfunction. UCP2 is also neuroprotective, reducing oxidative stress in neurons. UCP3 may also transport fatty acids out of mitochondria thereby protecting the mitochondria from fatty acid anions or peroxides. Current data suggest that UCP2 plays a role in the metabolic syndrome through down-regulation of insulin secretion and development of type-2 diabetes. However, UCP2 may protect against atherosclerosis through reduction of oxidative stress and both UCP2 and UCP3 may protect against obesity. Thus, these UCP1 homologues may both contribute to and protect from the markers of the metabolic syndrome.

  11. Insulin-dependent glucose metabolism in dairy cows with variable fat mobilization around calving.

    Science.gov (United States)

    Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Görs, S; Röntgen, M; Sauerwein, H; Bruckmaier, R M; Metges, C C; Kuhla, B; Hammon, H M

    2016-08-01

    Dairy cows undergo significant metabolic and endocrine changes during the transition from pregnancy to lactation, and impaired insulin action influences nutrient partitioning toward the fetus and the mammary gland. Because impaired insulin action during transition is thought to be related to elevated body condition and body fat mobilization, we hypothesized that over-conditioned cows with excessive body fat mobilization around calving may have impaired insulin metabolism compared with cows with low fat mobilization. Nineteen dairy cows were grouped according to their average concentration of total liver fat (LFC) after calving in low [LLFC; LFC 24.4% total fat/DM; n=10) fat-mobilizing cows. Blood samples were taken from wk 7 antepartum (ap) to wk 5 postpartum (pp) to determine plasma concentrations of glucose, insulin, glucagon, and adiponectin. We applied euglycemic-hyperinsulinemic (EGHIC) and hyperglycemic clamps (HGC) in wk 5 ap and wk 3 pp to measure insulin responsiveness in peripheral tissue and pancreatic insulin secretion during the transition period. Before and during the pp EGHIC, [(13)C6] glucose was infused to determine the rate of glucose appearance (GlucRa) and glucose oxidation (GOx). Body condition, back fat thickness, and energy-corrected milk were greater, but energy balance was lower in HLFC than in LLFC. Plasma concentrations of glucose, insulin, glucagon, and adiponectin decreased at calving, and this was followed by an immediate increase of glucagon and adiponectin after calving. Insulin concentrations ap were higher in HLFC than in LLFC cows, but the EGHIC indicated no differences in peripheral insulin responsiveness among cows ap and pp. However, GlucRa and GOx:GlucRa during the pp EGHIC were greater in HLFC than in LLFC cows. During HGC, pancreatic insulin secretion was lower, but the glucose infusion rate was higher pp than ap in both groups. Plasma concentrations of nonesterified fatty acids decreased during HGC and EGHIC, but in both

  12. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice.

    Science.gov (United States)

    Cani, Patrice D; Bibiloni, Rodrigo; Knauf, Claude; Waget, Aurélie; Neyrinck, Audrey M; Delzenne, Nathalie M; Burcelin, Rémy

    2008-06-01

    Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases. We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect. We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat-fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14(-)(/)(-) mutant mice mimicked the metabolic and inflammatory effects of antibiotics. This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.

  13. Adiposity and Fat Metabolism in Lactating and Fasting Northern Elephant Seals12

    Science.gov (United States)

    Crocker, Daniel E.; Champagne, Cory D.; Fowler, Melinda A.; Houser, Dorian S.

    2014-01-01

    Several taxa of animals fast completely from food and water during energy-intensive periods such as lactation, breeding, and development. In elephant seals, these behaviors are sustained by high adiposity, high rates of fat mobilization, and reduced oxidation of carbohydrates and proteins. Adiposity and the regulation of lipolysis directly affect lactation energetics, milk composition, and mating success. Long-term fasting induces changes in regulation of lipolysis and lipid metabolism that influence fatty acid (FA) availability and the onset of insulin resistance. Hypoinsulinemia and elevated circulating FAs are also associated with several unique features of carbohydrate metabolism, including elevated plasma glucose, gluconeogenesis, and Cori cycle activity as well as high rates of pyruvate and tricarboxylic acid cycling. Glucose-lactate pools and triacylglycerol-FA cycles may be linked via glyceroneogenesis and this may be an important pathway influencing both fat and carbohydrate metabolism. Together, these features allow a sustained, high intensity, fat-based metabolism without substantial accumulation of ketoacids. PMID:24425723

  14. Use of MRI and CT for fat imaging in children and youth: what have we learned about obesity, fat distribution and metabolic disease risk?

    Science.gov (United States)

    Samara, A; Ventura, E E; Alfadda, A A; Goran, M I

    2012-08-01

    Childhood obesity is a matter of great concern for public health. Efforts have been made to understand its impact on health through advanced imaging techniques. An increasing number of studies focus on fat distribution and its associations with metabolic risk, in interaction with genetics, environment and ethnicity, in children. The present review is a qualitative synthesis of the existing literature on visceral and subcutaneous abdominal, intrahepatic and intramuscular fat. Our search revealed 80 original articles. Abdominal as well as ectopic fat depots are prevalent already in childhood and contribute to abnormal metabolic parameters, starting early in life. Visceral, hepatic and intramuscular fat seem to be interrelated but their patterns as well as their independent contribution on metabolic risk are not clear. Some ethnic-specific characteristics are also prevalent. These results encourage further research in childhood obesity by using imaging techniques such as magnetic resonance imaging and computed tomography. These imaging methods can provide a better understanding of fat distribution and its relationships with metabolic risk, compared to less detailed fat and obesity assessment. However, studies on bigger samples and with a prospective character are warranted. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

  15. Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism.

    Directory of Open Access Journals (Sweden)

    David John Kennaway

    Full Text Available The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight. Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism.

  16. Effect of grass dry matter intake and fat supplementation on progesterone metabolism in lactating dairy cows.

    Science.gov (United States)

    Hutchinson, I A; Dewhurst, R J; Evans, A C O; Lonergan, P; Butler, S T

    2012-09-01

    Progesterone (P4) metabolism in dairy cattle can be manipulated by alterations in dry matter intake and diet composition. Our objectives were to determine the effects of grazing allowance and fat supplementation on P4 metabolism in lactating dairy cows. Forty mid- to late-lactation Holstein-Friesian dairy cows were used in a completely randomized block design, with a 2 × 2 factorial arrangement of treatments. Cows were assigned to receive 1 of 2 pasture allowances (ad libitum allowance [AL], 9.5 kg dry matter per day, or restricted allowance [R] 7 kg dry matter per day) and 1 of 2 fat supplementation treatments (750 g per day saturated fat [F] or no fat supplement [NF]). All cows received an additional 4 kg per day of concentrate. Grass dry matter intake (GDMI) was measured 5 wk after the initiation of dietary treatment. Cows were treated with prostaglandin F(2α) (PGF(2α)) to eliminate the endogenous source of P4, and two intravaginal progesterone-releasing devices (CIDR) were inserted into each cow for a period of 8 days. Regular blood samples were taken before and after the removal of the intravaginal progesterone-releasing devices, and analyzed for P4 concentrations. The half-life (t½) and metabolic clearance rate (MCR) of P4 was calculated for each cow. There was no effect of GDMI or fat supplementation on the t½ or MCR of P4. There was a tendency for an interaction between GDMI and fat supplementation on the t½ of P4; cows on the restricted-F diet tended to have a longer P4 t½ than cows on the ad libitum-F diet. It was concluded that greater alterations in GDMI than achieved in the current study are required to change P4 metabolism. A combination of fat supplementation and restricted feeding slows P4 clearance, which may have beneficial implications for fertility. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Comparative gene expression of intestinal metabolizing enzymes.

    Science.gov (United States)

    Shin, Ho-Chul; Kim, Hye-Ryoung; Cho, Hee-Jung; Yi, Hee; Cho, Soo-Min; Lee, Dong-Goo; Abd El-Aty, A M; Kim, Jin-Suk; Sun, Duxin; Amidon, Gordon L

    2009-11-01

    The purpose of this study was to compare the expression profiles of drug-metabolizing enzymes in the intestine of mouse, rat and human. Total RNA was isolated from the duodenum and the mRNA expression was measured using Affymetrix GeneChip oligonucleotide arrays. Detected genes from the intestine of mouse, rat and human were ca. 60% of 22690 sequences, 40% of 8739 and 47% of 12559, respectively. Total genes of metabolizing enzymes subjected in this study were 95, 33 and 68 genes in mouse, rat and human, respectively. Of phase I enzymes, the mouse exhibited abundant gene expressions for Cyp3a25, Cyp4v3, Cyp2d26, followed by Cyp2b20, Cyp2c65 and Cyp4f14, whereas, the rat showed higher expression profiles of Cyp3a9, Cyp2b19, Cyp4f1, Cyp17a1, Cyp2d18, Cyp27a1 and Cyp4f6. However, the highly expressed P450 enzymes were CYP3A4, CYP3A5, CYP4F3, CYP2C18, CYP2C9, CYP2D6, CYP3A7, CYP11B1 and CYP2B6 in the human. For phase II enzymes, glucuronosyltransferase Ugt1a6, glutathione S-transferases Gstp1, Gstm3 and Gsta2, sulfotransferase Sult1b1 and acyltransferase Dgat1 were highly expressed in the mouse. The rat revealed predominant expression of glucuronosyltransferases Ugt1a1 and Ugt1a7, sulfotransferase Sult1b1, acetyltransferase Dlat and acyltransferase Dgat1. On the other hand, in human, glucuronosyltransferases UGT2B15 and UGT2B17, glutathione S-transferases MGST3, GSTP1, GSTA2 and GSTM4, sulfotransferases ST1A3 and SULT1A2, acetyltransferases SAT1 and CRAT, and acyltransferase AGPAT2 were dominantly detected. Therefore, current data indicated substantial interspecies differences in the pattern of intestinal gene expression both for P450 enzymes and phase II drug-metabolizing enzymes. This genomic database is expected to improve our understanding of interspecies variations in estimating intestinal prehepatic clearance of oral drugs.

  18. Molecular effect of fenofibrate on PBMC gene transcription related to lipid metabolism in patients with metabolic syndrome.

    Science.gov (United States)

    Moreno-Indias, I; Tinahones, F J; Clemente-Postigo, M; Castellano-Castillo, D; Fernández-García, J C; Macias-Gonzalez, M; Queipo-Ortuño, M I; Cardona, F

    2017-06-01

    Both fasting and postprandial hypertriglyceridaemia are considered independent risk factors for atherosclerosis. Treatment of hypertriglyceridaemia is based on fibrates, which activate the peroxisome proliferator-activated receptor alpha (PPARα). However, the metabolic pathways that activate or inhibit fibrates, and how the postprandial triglyceride levels are modified, have not yet been fully described. Accordingly, the aim of this study was to determine the feasibility of peripheral blood mononuclear cells (PBMC) to study the effects of fenofibrate in patients with the metabolic syndrome. A fat overload was given to 50 patients before and after treatment with fenofibrate for 3 months. Anthropometric and biochemical variables as well as gene expression in PBMC were analysed. After treatment with fenofibrate, we observed a decrease in both baseline and postprandial (3 h after the fat overload) levels of serum triglycerides, cholesterol and uric acid and an increase in HDL cholesterol and apolipoprotein AI levels. After treatment, there was also a rise in PPARα and RXRα expression and changes in genes regulated by PPARα, both baseline and postprandial. Furthermore, in vitro experiments showed that a PPARα agonist changed the expression of genes related with lipid metabolism. Treatment with fenofibrate reduced fasting and postprandial serum triglyceride levels, possibly through a mechanism related with an increase in the expression of RXRα and PPARα, by activating the pathways involved in the uptake and degradation of triglycerides and increasing the synthesis of apolipoprotein. These results suggest that PBMC may be useful for the easy study of fenofibrate actions. © 2017 John Wiley & Sons Ltd.

  19. Epicardial adipose tissue is associated with visceral fat, metabolic syndrome, and insulin resistance in menopausal women.

    Science.gov (United States)

    Fernández Muñoz, María J; Basurto Acevedo, Lourdes; Córdova Pérez, Nydia; Vázquez Martínez, Ana Laura; Tepach Gutiérrez, Nayive; Vega García, Sara; Rocha Cruz, Alberto; Díaz Martínez, Alma; Saucedo García, Renata; Zárate Treviño, Arturo; González Escudero, Eduardo Alberto; Degollado Córdova, José Antonio

    2014-06-01

    Epicardial adipose tissue has been associated with several obesity-related parameters and with insulin resistance. Echocardiographic assessment of this tissue is an easy and reliable marker of cardiometabolic risk. However, there are insufficient studies on the relationship between epicardial fat and insulin resistance during the postmenopausal period, when cardiovascular risk increases in women. The objective of this study was to examine the association between epicardial adipose tissue and visceral adipose tissue, waist circumference, body mass index, and insulin resistance in postmenopausal women. A cross sectional study was conducted in 34 postmenopausal women with and without metabolic syndrome. All participants underwent a transthoracic echocardiogram and body composition analysis. A positive correlation was observed between epicardial fat and visceral adipose tissue, body mass index, and waist circumference. The values of these correlations of epicardial fat thickness overlying the aorta-right ventricle were r = 0.505 (P < .003), r = 0.545 (P < .001), and r = 0.515 (P < .003), respectively. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome than in those without this syndrome (mean [standard deviation], 544.2 [122.9] vs 363.6 [162.3] mm(2); P = .03). Epicardial fat thickness measured by echocardiography was associated with visceral adipose tissue and other obesity parameters. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome. Therefore, echocardiographic assessment of epicardial fat may be a simple and reliable marker of cardiovascular risk in postmenopausal women. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  20. Association of a cholesteryl ester transfer protein variant (rs1800777) with fat mass, HDL cholesterol levels, and metabolic syndrome.

    Science.gov (United States)

    de Luis, Daniel; Izaola, Olatz; Primo, David; Gomez, Emilia; Lopez, Juan Jose; Ortola, Ana; Aller, Rocio

    2018-04-25

    There is little evidence of the association between CETP SNPs and obesity and/or related metabolic parameters. To analyze the association of the polymorphism rs1800777 of the CETP gene with anthropometric parameters, lipid profile, metabolic syndrome and its components, and adipokine levels in obese subjects without type 2 diabetes mellitus or hypertension. A population of 1005 obese subjects was analyzed. Electrical bioimpedance was performed, and blood pressure, presence of metabolic syndrome, dietary intake, physical activity, and biochemical tests were recorded. Nine hundred and sixty eight patients (96.3%) had the GG genotype, 37 patients the GA genotype (3.7%) (no AA genotype was detected). Fat mass (delta: 4.4±1.1kg; p=0.04), waist circumference (delta: 5.6±2.1cm; p=0.02), and waist to hip ratio (delta: 0.04±0.01cm; p=0.01) were higher in A allele carriers than in non-A allele carriers. HDL cholesterol levels were lower in A allele carriers than in non-A allele carriers (delta: 4.2±1.0mg/dL; p=0.04). In the logistic regression analysis, the GA genotype was associated to an increased risk of central obesity (OR 7.55, 95% CI 1.10-55.70, p=0.02) and low HDL cholesterol levels (OR 2.46, 95% CI 1.23-4.91, p=0.014). The CETP variant at position +82 is associated to lower HDL cholesterol levels, increased fat mass, and central obesity in obese subjects. These results may suggest a potential role of this variant gene in pathophysiology of adipose tissue. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Subcutaneous to visceral fat ratio: a possible risk factor for metabolic syndrome and cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Shafqat MN

    2018-04-01

    Full Text Available Muhammad Nabeel Shafqat,1 Miqdad Haider,2 1Department of Medicine, University of Medical Sciences “Serafin Ruiz de Zarate” Villa Clara (UCMVC, Villa Clara, Cuba; 2Department of Internal Medicine, Fatima Memorial Hospital, Fatima Memorial College of Medicine and Dentistry, Lahore, PakistanWe would like to comment, with great interest, about the recently published article “Visceral-to-subcutaneous fat ratio as a predictor of the multiple metabolic risk factors for subjects with normal waist circumference in Korea” by Oh et al,1 which we found very interesting and valuable. This study is a good step to determine the predictive value of visceral-to-subcutaneous fat ratio (VSR in persons with normal waist circumference for the diagnosis of risk factors for metabolic syndrome.View the original paper by Oh and colleagues.

  2. Muscle lipid metabolism in two rabbit lines divergently selected for intramuscular fat.

    Science.gov (United States)

    Martínez-Álvaro, M; Agha, S; Blasco, A; Hernández, P

    2017-06-01

    A divergent selection experiment for intramuscular fat (IMF) of LM at 9 wk of age was performed in rabbits. The objective of this work was to compare the lipid metabolism in muscles and fat tissues of the high-IMF and low-IMF lines. Lipogenic, catabolic, and lipolytic activities were studied in 2 muscles with different oxidative patterns (LM and semimembranosus proprius) and in the perirenal fat depot at 2 ages, 9 and 13 wk. In addition, adipocytes were characterized in perirenal fat. In the fifth generation, direct response to selection was 0.26 g IMF/100 g muscle. Lines showed differences in their lipogenic activities of muscles and fat tissues at 13 wk but not at 9 wk. The high-IMF line showed greater glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (EM), and fatty acid synthase (FAS) activities in LM than the low-IMF line, with probabilities = 1.00, 0.93, and 0.90, respectively. Differences between lines were particularly great for G6PDH activity, representing 1.13 SD. The high-IMF line also showed greater G6PDH and FAS activities in semimembranosus proprius (P = 0.98 for G6PDH and 0.95 for FAS) and perirenal fat (P = 0.91 for G6PDH and 0.96 for FAS). However, in perirenal fat, EM activity was greater in the low-IMF line (P = 0.90). No differences between lines were found in almost any catabolic or lipolytic activities of muscles. Regarding adipocyte characteristics, the high-IMF line showed larger adipocytes in perirenal fat depot tissue (P = 0.97) compared to the low-IMF line, but no differences between lines were observed in the number of adipocytes. This study sheds light on the metabolic activities involved in the genetic differentiation of lipid deposition in rabbits. This study shows that lipogenic activities in muscles and fat tissues, in particular G6PDH in LM, are involved in the lipid accumulation in muscle and adipose tissues.

  3. Body fat distribution in pre-and post-menopausal women: metabolic and anthropometric variables.

    Science.gov (United States)

    Garaulet, M; Pérez-Llamas, F; Baraza, J C; Garcia-Prieto, M D; Fardy, P S; Tébar, F J; Zamora, S

    2002-01-01

    Abdominal obesity is associated with coronary risk although the causality is not well established. To compare body fat distribution and metabolic variables in obese pre- and post- menopausal women. The study was conducted in 55 obese female subjects (22 pre- and 33 post- menopausal) with body mass indices (BMI) from 27 to 35 Kg/m2. Body fat distribution was measured using waist and hip circumference and computerized tomography. Hormones such as estradiol, testosterone, androstenedione, dehydroepiandrosterone-sulfate, as well as plasma lipids such as triglycerides, total cholesterol, high density lipoprotein, low density lipoprotein, apoproteins A and B, were also determined. No significant differences were found between the two groups in BMI, percentage of body fat, waist circumference, triceps, biceps, suprailiac and abdominal skinfolds. Hip circumference, subscapular skinfold and subcutaneous abdominal adipose tissue area were significantly lower, and waist-hip ratio, visceral area and visceral to subcutaneous area ratios significantly higher in post- menopausal women (P low density lipoprotein, values were significantly higher in the post-menopausal group (P fat distribution changes according to menopausal status, with central obesity more pronounced in post- menopausal women. Metabolic abnormalities are related more to visceral adipose tissue and estrogen plasma levels than to BMI.

  4. The relationship between fat depot-specific preadipocyte differentiation and metabolic syndrome in obese women

    Directory of Open Access Journals (Sweden)

    N V Mazurina

    2013-03-01

    Full Text Available Реферат по материалам статьи The relationship between fat depot-specific preadipocyte differentiation and metabolic syndrome in obese women. Park HТ, Lee ES, Cheon EP, Lee DR, Yang K-S, Kim YT, Hur JY, Kim SH, Lee KW, Kim T. Clinical Endocrinology 2012; 76, 59-66.

  5. Associations of Leg Fat Accumulation with Adiposity-Related Biological Factors and Risk of Metabolic Syndrome

    Science.gov (United States)

    Zhang, Xiaomin; Hu, Emily A.; Wu, Hongyu; Malik, Vasanti; Sun, Qi

    2012-01-01

    The association between regional fat mass distribution and cardiometabolic risk factors has been inconsistent in the literature, and data for ethnic minority groups, such as non-Hispanic blacks and Hispanics, are lacking. We aimed to examine this association among 8802 US residents who participated in the 1999-2004 US National Health and Nutrition Examination Survey (NHANES). Body composition was measured using dual-energy X-ray absorptiometry (DXA). Leg fat indices included leg fat mass (FM), leg fat mass percent (FM%), leg to whole body FM ratio (leg/whole) and leg to trunk FM ratio (leg/trunk). We evaluated the correlation between leg fat indices and adiposity-related risk factors, as well as the association of these indices with metabolic syndrome (MetS). After adjusting for covariates including age, gender, and trunk FM or trunk FM%, higher leg FM and leg FM% were, in general, correlated favorably with adiposity-related risk factors and associated with lower odds of MetS in all ethnicities, including non-Hispanic whites and blacks and Hispanic groups. In addition, in all multivariate-adjusted models, leg/whole and leg/trunk ratios were strongly associated with lower levels of most risk factors and decreased odds of MetS in these ethnicities (all odds ratios comparing extreme quintiles leg fat accumulation is inversely associated with adiposity-related biological factors and risk of MetS in both whites and ethnic groups, suggesting that regional fat distribution plays an important role in the etiology of adiposity-related diseases in these populations. PMID:23404933

  6. The Effect of Casein Protein Prior to Sleep on Fat Metabolism in Obese Men

    Directory of Open Access Journals (Sweden)

    Amber W. Kinsey

    2016-07-01

    Full Text Available We have previously shown that ingesting protein at night before sleep is either beneficial or non-detrimental to metabolism, health, and body composition in obese women. However, the overnight protein-induced lipolytic actions and mechanism for improved metabolism and body composition have not been fully established. Therefore, in a crossover design, twelve obese men (age, 27.0 ± 2.2 years were randomly assigned to ingest (within 30 min of sleep casein protein (CAS, 120 kcal or a non-nutritive placebo (PLA before going to sleep. Markers of fat metabolism (lipolysis, substrate utilization, growth hormone, insulin, glucose, resting energy expenditure (REE, and appetite (questionnaire and ghrelin were measured. During sleep and the next morning, interstitial glycerol from the subcutaneous abdominal adipose tissue (SCAAT was measured using microdialysis. There were no differences in SCAAT glycerol (overnight: CAS, 177.4 ± 26.7; PLA, 183.8 ± 20.2 μmol/L; morning: CAS, 171.6 ± 19.1; PLA, 161.5 ± 18.6 μmol/L, substrate utilization, REE, or any blood markers between CAS and PLA. Desire to eat was greater for CAS compared to baseline (p = 0.03, but not different from PLA (baseline: 39 ± 6, CAS: 62 ± 8, PLA: 55 ± 5 mm. CAS consumption before sleep did not affect fat or glucose metabolism, REE, or suppress appetite in hyperinsulemic obese men. CAS may be consumed before sleep without impeding overnight or morning fat metabolism in young, obese men.

  7. Variations in insulin responsiveness in rat fat cells are due to metabolic differences rather than insulin binding

    DEFF Research Database (Denmark)

    Hansen, Finn Mølgård; Nilsson, Poul; Sonne, Ole

    1983-01-01

    -insulin to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism...

  8. Weight gain induced by an isocaloric pair-fed high fat diet: a nutriepigenetic study on FASN and NDUFB6 gene promoters.

    Science.gov (United States)

    Lomba, Almudena; Martínez, J Alfredo; García-Díaz, Diego F; Paternain, Laura; Marti, Amelia; Campión, Javier; Milagro, Fermín I

    2010-01-01

    Experimental studies have demonstrated that dietary macronutrient distribution plays an important role in insulin regulation, a risk factor associated to obesity, diabetes and other metabolic disorders. To assess whether the macronutrient composition of the diet could be related to obesity onset by affecting the epigenetic regulation of gene expression, we investigated in rats the metabolic effects of two pair-fed isocaloric diets: control (rich in carbohydrates) and high fat diet (rich in fat; HFD). Compared to controls, HFD induced higher weight gain and adiposity and impaired glucose tolerance, which was accompanied by a slight increase in adiponectin levels and liver steatosis. Epididymal adipose tissue expression of the fatty acid synthase (FASN) gene and NADH dehydrogenase (ubiquinone) 1β-subcomplex 6 (NDUFB6) were significantly reduced in HFD group. These variations in mRNA levels were accompanied by changes in the methylation patterns of several CpG islands located in the promoter region of these genes. However, no correlations were found between gene expression and the methylation status. These results suggest that high fat intake produces overweighted rats independently of total energy intake. These diets could also induce some epigenetic changes in the promoters of key genes that could influence gene expression and may be behind metabolic alterations. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Effects of fat and exoskeletal mass on the mass scaling of metabolism in Carabidae beetles.

    Science.gov (United States)

    Schramm, Bartosz W; Gudowska, Agnieszka; Antoł, Andrzej; Labecka, Anna Maria; Bauchinger, Ulf; Kozłowski, Jan; Czarnoleski, Marcin

    2017-10-13

    The rate at which organisms metabolize resources and consume oxygen is tightly linked to body mass. Typically, there is a sub-linear allometric relationship between metabolic rates and body mass (mass-scaling exponent b scaling of metabolic rates. Contrary to our hypothesis, the relative contribution of fat and the exoskeleton to body mass decreased, rather than increased with body mass, as indicated by the sub-linear allometric mass scaling of both components (b scaling, the exponents (b) for metabolism became slightly smaller (b = 0.70, phylogeny not considered; 0.52, phylogeny considered) when we removed lipids and the exoskeleton from body mass calculations and considered only the lean mass of soft tissue in the mass scaling. Overall, our results indicate that, in beetles, the relative content of metabolically inert components changes across species according to species-specific body mass. Nevertheless, we did not find evidence that this changing contribution plays a central role in the origin of interspecific metabolic scaling in carabids. Our findings stress the need for finding alternative explanations, at least in carabids, for the origin of the mass scaling of metabolic rates. Copyright © 2017. Published by Elsevier Ltd.

  10. Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

    Science.gov (United States)

    Schmid, Alexandra; Petry, Nicolai; Walther, Barbara; Bütikofer, Ueli; Luginbühl, Werner; Gille, Doreen; Chollet, Magali; McTernan, Philip G; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François P; Laederach, Kurt; Vergères, Guy

    2015-06-28

    Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

  11. Deep Sequencing and Screening of Differentially Expressed MicroRNAs Related to Milk Fat Metabolism in Bovine Primary Mammary Epithelial Cells.

    Science.gov (United States)

    Shen, Binglei; Zhang, Liying; Lian, Chuanjiang; Lu, Chunyan; Zhang, Yonghong; Pan, Qiqi; Yang, Runjun; Zhao, Zhihui

    2016-02-17

    Milk fat is a key factor affecting milk quality and is also a major trait targeted in dairy cow breeding. To determine how the synthesis and the metabolism of lipids in bovine milk is regulated at the miRNA level, primary mammary epithelial cells (pMEC) derived from two Chinese Holstein dairy cows that produced extreme differences in milk fat percentage were cultured by the method of tissue nubbles culture. Small RNA libraries were constructed from each of the two pMEC groups, and Solexa sequencing and bioinformatics analysis were then used to determine the abundance of miRNAs and their differential expression pattern between pMECs. Target genes and functional prediction of differentially expressed miRNAs by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis illustrated their roles in milk fat metabolism. Results show that a total of 292 known miRNAs and 116 novel miRNAs were detected in both pMECs. Identification of known and novel miRNA candidates demonstrated the feasibility and sensitivity of sequencing at the cellular level. Additionally, 97 miRNAs were significantly differentially expressed between the pMECs. Finally, three miRNAs including bta-miR-33a, bta-miR-152 and bta-miR-224 whose predicted target genes were annotated to the pathway of lipid metabolism were screened and verified by real-time qPCR and Western-blotting experiments. This study is the first comparative profiling of the miRNA transcriptome in pMECs that produce different milk fat content.

  12. Deep Sequencing and Screening of Differentially Expressed MicroRNAs Related to Milk Fat Metabolism in Bovine Primary Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Binglei Shen

    2016-02-01

    Full Text Available Milk fat is a key factor affecting milk quality and is also a major trait targeted in dairy cow breeding. To determine how the synthesis and the metabolism of lipids in bovine milk is regulated at the miRNA level, primary mammary epithelial cells (pMEC derived from two Chinese Holstein dairy cows that produced extreme differences in milk fat percentage were cultured by the method of tissue nubbles culture. Small RNA libraries were constructed from each of the two pMEC groups, and Solexa sequencing and bioinformatics analysis were then used to determine the abundance of miRNAs and their differential expression pattern between pMECs. Target genes and functional prediction of differentially expressed miRNAs by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis illustrated their roles in milk fat metabolism. Results show that a total of 292 known miRNAs and 116 novel miRNAs were detected in both pMECs. Identification of known and novel miRNA candidates demonstrated the feasibility and sensitivity of sequencing at the cellular level. Additionally, 97 miRNAs were significantly differentially expressed between the pMECs. Finally, three miRNAs including bta-miR-33a, bta-miR-152 and bta-miR-224 whose predicted target genes were annotated to the pathway of lipid metabolism were screened and verified by real-time qPCR and Western-blotting experiments. This study is the first comparative profiling of the miRNA transcriptome in pMECs that produce different milk fat content.

  13. Effects of dietary fat and oxidized cholesterol on gene expression in rat liver as assessed by cDNA expression array analysis.

    Science.gov (United States)

    Ringseis, Robert; Eder, Klaus

    2005-06-01

    Specific oxysterols acting as ligands for nuclear transcription factors were shown to affect expression of genes involved in lipid metabolism. However, the various biological effects of oxysterols such as cytotoxicity, atherogenicity or mutagenicity suggest that other genes may be also affected by oxysterols than lipid metabolism. The present study was conducted to investigate the effects of dietary oxidized cholesterol containing significant amounts of oxysterols and its interactions with different dietary fats on gene expression profiles as assessed by DNA array technology in rats. 54 male Sprague-Dawley rats were assigned to six groups and were fed six semisynthetic diets, which varied in the type of dietary fat (coconut oil vs. salmon oil) and dietary cholesterol (none cholesterol vs. 5 g unoxidized cholesterol/kg vs. 5 g oxidized cholesterol/kg). Changes in gene expression as observed in response to dietary oxidized cholesterol were strongly dependent on the type of fat. In the rats fed coconut oil, the expression of 7 genes (5 up- and 2 down-regulated) was altered by dietary oxidized cholesterol, while in the rats fed salmon oil, the expression of 50 genes (16 up- and 34 down-regulated) was altered. 29 genes (22 up- and 7 down-regulated) were identified as possible targets for an altered gene expression by dietary salmon oil as compared to dietary coconut oil. The present study showed that dietary oxidized cholesterol transcriptionally affects many genes involved in xenobiotic metabolism and stress response--an effect that was amplified by the administration of fish oil as dietary fat.

  14. Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

    Science.gov (United States)

    2017-08-31

    Metabolism, Inborn Errors; Lipid Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogenin-1 Deficiency (Glycogen Storage Disease Type XV); Carnitine Palmitoyl Transferase 2 Deficiency; VLCAD Deficiency; Medium-chain Acyl-CoA Dehydrogenase Deficiency; Multiple Acyl-CoA Dehydrogenase Deficiency; Carnitine Transporter Deficiency; Neutral Lipid Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Muscle Phosphofructokinase Deficiency; Phosphoglucomutase 1 Deficiency; Phosphoglycerate Mutase Deficiency; Phosphoglycerate Kinase Deficiency; Phosphorylase Kinase Deficiency; Beta Enolase Deficiency; Lactate Dehydrogenase Deficiency; Glycogen Synthase Deficiency

  15. Effects of Gliadin consumption on the Intestinal Microbiota and Metabolic Homeostasis in Mice Fed a High-fat Diet

    DEFF Research Database (Denmark)

    Zhang, Li; Andersen, Daniel; Roager, Henrik Munch

    2017-01-01

    compartments, gut barrier function, gene expression, urinary metabolites and immune profiles in intestinal, lymphoid, liver and adipose tissues was performed. Mice fed the gliadin-containing HFD displayed higher glycated hemoglobin and higher insulin resistance as evaluated by the homeostasis model assessment......, more hepatic lipid accumulation and smaller adipocytes than mice fed the gliadin-free HFD. This was accompanied by alterations in the composition and activity of the gut microbiota, gut barrier function, urine metabolome, and immune phenotypes within liver and adipose tissue. Our results reveal...... that gliadin disturbs the intestinal environment and affects metabolic homeostasis in obese mice, suggesting a detrimental effect of gluten intake in gluten-tolerant subjects consuming a high-fat diet....

  16. NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program

    DEFF Research Database (Denmark)

    Hiraike, Yuta; Waki, Hironori; Yu, Jing

    2017-01-01

    Brown fat dissipates energy as heat and protects against obesity. Here, we identified nuclear factor I-A (NFIA) as a transcriptional regulator of brown fat by a genome-wide open chromatin analysis of murine brown and white fat followed by motif analysis of brown-fat-specific open chromatin region....... These results indicate that NFIA activates the cell-type-specific enhancers and facilitates the binding of PPARγ to control the brown fat gene program.......Brown fat dissipates energy as heat and protects against obesity. Here, we identified nuclear factor I-A (NFIA) as a transcriptional regulator of brown fat by a genome-wide open chromatin analysis of murine brown and white fat followed by motif analysis of brown-fat-specific open chromatin regions....... NFIA and the master transcriptional regulator of adipogenesis, PPARγ, co-localize at the brown-fat-specific enhancers. Moreover, the binding of NFIA precedes and facilitates the binding of PPARγ, leading to increased chromatin accessibility and active transcription. Introduction of NFIA into myoblasts...

  17. Soy protein diet alters expression of hepatic genes regulating fatty acid and thyroid hormone metabolism in the male rat

    Science.gov (United States)

    We determined effects of soy protein (SPI) and the isoflavone genistein (GEN) on mRNA expression of key lipid metabolism and thyroid hormone system genes in young adult, male Sprague-Dawley rats. SPI-fed rats had less retroperitoneal fat and less hepato-steatosis than casein (CAS, control protein)-...

  18. Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in high-fat fed mice.

    Science.gov (United States)

    Gu, Yeyi; Yu, Shan; Park, Jong Yung; Harvatine, Kevin; Lambert, Joshua D

    2014-04-01

    In diet-induced obesity, adipose tissue (AT) is in a chronic state of inflammation predisposing the development of metabolic syndrome. Cocoa (Theobroma cacao) is a polyphenol-rich food with putative anti-inflammatory activities. Here, we examined the impact and underlying mechanisms of action of cocoa on AT inflammation in high fat-fed mice. In the present study, male C57BL/6 J mice were fed a high fat diet (HF), a HF diet with 8% (w/w) unsweetened cocoa powder (HFC), or a low-fat diet (LF) for 18 weeks. Cocoa supplementation decreased AT mRNA levels of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and EGF-like module-containing mucin-like hormone receptor-like 1 by 40-60% compared to HF group, and this was accompanied by decreased nuclear protein levels of nuclear factor-κB. Cocoa treatment reduced the levels of arachidonic acid in the AT by 33% compared to HF controls. Moreover, cocoa treatment also reduced protein levels of the eicosanoid-generating enzymes, adipose-specific phospholipase A2 and cyclooxygenase-2 by 53% and 55%, respectively, compared to HF-fed mice. Finally, cocoa treatment ameliorated metabolic endotoxemia (40% reduction in plasma endotoxin) and improved gut barrier function (as measured by increased plasma levels of glucagon-like peptide-2). In conclusion, the present study has shown for the first time that long-term cocoa supplementation can reduce AT inflammation in part by modulating eicosanoid metabolism and metabolic endotoxemia. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Metabolic risk factors in mice divergently selected for BMR fed high fat and high carb diets.

    Science.gov (United States)

    Sadowska, Julita; Gębczyński, Andrzej K; Konarzewski, Marek

    2017-01-01

    Factors affecting contribution of spontaneous physical activity (SPA; activity associated with everyday tasks) to energy balance of humans are not well understood, as it is not clear whether low activity is related to dietary habits, precedes obesity or is a result of thereof. In particular, human studies on SPA and basal metabolic rates (BMR, accounting for >50% of human energy budget) and their associations with diet composition, metabolic thrift and obesity are equivocal. To clarify these ambiguities we used a unique animal model-mice selected for divergent BMR rates (the H-BMR and L-BMR line type) presenting a 50% between-line type difference in the primary selected trait. Males of each line type were divided into three groups and fed either a high fat, high carb or a control diet. They then spent 4 months in individual cages under conditions emulating human "sedentary lifestyle", with SPA followed every month and measurements of metabolic risk indicators (body fat mass %, blood lipid profile, fasting blood glucose levels and oxidative damage in the livers, kidneys and hearts) taken at the end of study. Mice with genetically determined high BMR assimilated more energy and had higher SPA irrespective of type of diet. H-BMR individuals were characterized by lower dry body fat mass %, better lipid profile and lower fasting blood glucose levels, but higher oxidative damage in the livers and hearts. Genetically determined high BMR may be a protective factor against diet-induced obesity and most of the metabolic syndrome indicators. Elevated spontaneous activity is correlated with high BMR, and constitutes an important factor affecting individual capability to sustain energy balance even under energy dense diets.

  20. Transcriptomic Analysis Identifies Candidate Genes Related to Intramuscular Fat Deposition and Fatty Acid Composition in the Breast Muscle of Squabs (Columba

    Directory of Open Access Journals (Sweden)

    Manhong Ye

    2016-07-01

    Full Text Available Despite the fact that squab is consumed throughout the world because of its high nutritional value and appreciated sensory attributes, aspects related to its characterization, and in particular genetic issues, have rarely been studied. In this study, meat traits in terms of pH, water-holding capacity, intramuscular fat content, and fatty acid profile of the breast muscle of squabs from two meat pigeon breeds were determined. Breed-specific differences were detected in fat-related traits of intramuscular fat content and fatty acid composition. RNA-Sequencing was applied to compare the transcriptomes of muscle and liver tissues between squabs of two breeds to identify candidate genes associated with the differences in the capacity of fat deposition. A total of 27 differentially expressed genes assigned to pathways of lipid metabolism were identified, of which, six genes belonged to the peroxisome proliferator-activated receptor signaling pathway along with four other genes. Our results confirmed in part previous reports in livestock and provided also a number of genes which had not been related to fat deposition so far. These genes can serve as a basis for further investigations to screen markers closely associated with intramuscular fat content and fatty acid composition in squabs. The data from this study were deposited in the National Center for Biotechnology Information (NCBI’s Sequence Read Archive under the accession numbers SRX1680021 and SRX1680022. This is the first transcriptome analysis of the muscle and liver tissue in Columba using next generation sequencing technology. Data provided here are of potential value to dissect functional genes influencing fat deposition in squabs.

  1. Preproghrelin gene polymorphisms in obese Japanese women. Minor homozygotes are light eaters, do not prefer protein or fat, and apparently have a poor appetite.

    Science.gov (United States)

    Takezawa, Jun; Yamada, Kouichi; Miyachi, Motohiko; Morita, Akemi; Aiba, Naomi; Sasaki, Satoshi; Watanabe, Shaw

    2013-04-01

    Preproghrelin gene single-nucleotide polymorphisms are possible predisposing factors to obesity and other metabolic syndromes. To study the correlation between genotypes and obesity, we recruited 117 obese Japanese women (BMI, 25.0-41.1; average, 31.1). Minor homozygotes for five preproghrelin gene polymorphisms, namely, -1500C>G (rs3755777), -1062G>C (rs26311), -994C>T (rs26312) (promoter region), Leu72Met (rs696217) (exon 2), and +3056T>C (rs2075356) (intron 2), had high values of total and visceral fat areas, waist circumference, and BMI, indicating significant correlation of the polymorphisms with obesity and fat metabolism. Here, we studied the relationship between the genotypes and dietary tendency. Self-administered Diet History Questionnaire showed that total food intake, sugar, and dairy product intake were low in +3056C/C women. Their energy, protein, fat, and meat intake was also low. Energy balance calculation showed considerably reduced fat and protein consumption. Dietary habits were surveyed using Sakata's Questionnaire on Eating Behavior. Of the genotypes, -1062C/C women showed low scores for "motivation for eating" and "eating because of stress or something else." Thus, surprisingly, it was revealed that minor homozygotes for preproghrelin gene polymorphisms were light eaters, did not prefer fat or protein, and apparently had a poor appetite, although they were predisposed to obesity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. High Phenolics Rutgers Scarlet Lettuce Improves Glucose Metabolism in High Fat Diet-Induced Obese Mice

    Science.gov (United States)

    Cheng, Diana M.; Roopchand, Diana E.; Poulev, Alexander; Kuhn, Peter; Armas, Isabel; Johnson, William D.; Oren, Andrew; Ribnicky, David; Zelzion, Ehud; Bhattacharya, Debashish; Raskin, Ilya

    2016-01-01

    Scope The ability of high phenolic Rutgers Scarlet Lettuce (RSL) to attenuate metabolic syndrome and gut dysbiosis was studied in very high fat diet (VHFD)-fed mice. Phenolic absorption was assessed in vivo and in a gastrointestinal tract model. Methods and results Mice were fed VHFD, VHFD supplemented with RSL (RSL-VHFD) or store-purchased green lettuce (GL-VHFD), or low-fat diet (LFD) for 13 weeks. Compared to VHFD or GL-VHFD-fed groups, RSL-VHFD group showed significantly improved oral glucose tolerance (p<0.05). Comparison of VHFD, RSL-VHFD, and GL-VHFD groups revealed no significant differences with respect to insulin tolerance, hepatic lipids, body weight gain, fat mass, plasma glucose, triglycerides, free fatty acid, and lipopolysaccharide levels, as well as relative abundances of major bacterial phyla from 16S rDNA amplicon data sequences (from fecal and cecal samples). However, RSL and GL-supplementation increased abundance of several taxa involved in plant polysaccharide degradation/fermentation. RSL phenolics chlorogenic acid, quercetin-3-glucoside, and quercetin-malonyl-glucoside were bioaccessible in the TIM-1 digestion model, but had relatively low recovery. Conclusions RSL phenolics contributed to attenuation of postprandial hyperglycemia. Changes in gut microbiota were likely due to microbiota accessible carbohydrates in RSL and GL rather than RSL phenolics, which may be metabolized, absorbed, or degraded before reaching the colon. PMID:27529448

  3. Androgen receptor gene polymorphisms and maximal fat oxidation in healthy men. A longitudinal study.

    Science.gov (United States)

    Ponce González, Jesús Gustavo; Guadalupe-Grau, Amelia; Rodríguez-González, Francisco Germán; Torres-Peralta, Rafael; Morales-Alamo, David; Rodríguez-García, Lorena; Díaz-Chico, Bonifacio Nicolás; López Calbet, José Antonio; Dorado, Cecilia

    2017-10-24

    Androgens play a major role in fat oxidation; however, the effects of androgens depend, among other factors, on the intrinsic characteristics of the androgen receptor (AR). Lower repetitions of CAG and GGN polymorphism appear to have a protective effect on fat accumulation in the transition from adolescent to mid-twenties. Whether a similar protective effect is present later in life remains unknown. The aims of this study were: a) to evaluate if extreme CAG and GGN repeat polymorphisms of the androgen receptors influence body fat mass, its regional distribution, resting metabolic rate (RMR), maximal fat oxidation capacity (MFO) and serum leptin, free testosterone and osteocalcin in healthy adult men; and b) to determine the longitudinal effects on fat tissue accumulation after 6.4 years of follow-up. CAG and GGN repeats length were measured in 319 healthy men (mean ± standard deviation [SD]: 28.3 ± 7.6 years). From these, we selected the subjects with extreme short (CAGS or equal 24; n = 10) CAG repeats, and the subjects with short (GGNS or equal to 25; n = 10) GGN repeats. Body composition was assessed by DXA and serum levels of leptin, free testosterone and osteocalcin by ELISA. After 6.4 years of follow-up, DXA was repeated, and resting metabolic rate (RMR), MFO and VO2max determined by indirect calorimetry. CAGS and CAGL subjects had similar RMR and accumulated comparable amounts of fat tissue over 6.4 ± 1.0 years of follow-up. However, CAGL had higher MFO and total lean mass than CAGS (p fat mass than men with GGNL, particularly in the trunk region seven years later. This concurred with a greater MFO in the GGNL group (p fat mass. Free testosterone was associated with MFO in absolute values (r = 0.45; p fat oxidation capacity and may have a role in the accumulation of fat over the years.

  4. High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome.

    Science.gov (United States)

    Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong

    2014-11-01

    Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS. © 2014 by the Society for the Study of Reproduction, Inc.

  5. Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.

    Science.gov (United States)

    Salomäki, Henriikka; Heinäniemi, Merja; Vähätalo, Laura H; Ailanen, Liisa; Eerola, Kim; Ruohonen, Suvi T; Pesonen, Ullamari; Koulu, Markku

    2014-01-01

    Despite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. Female mice were on a high fat diet (HFD) prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD) and subjected to HFD at adulthood (10-11 weeks). Body weight and several metabolic parameters (e.g. body composition and glucose tolerance) were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment. Prenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC) was prominently affected both in the neonatal liver and adipose tissue. This study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood.

  6. Integration of Genome Scale Metabolic Networks and Gene Regulation of Metabolic Enzymes With Physiologically Based Pharmacokinetics

    Science.gov (United States)

    Maldonado, Elaina M.; Leoncikas, Vytautas; Fisher, Ciarán P.; Moore, J. Bernadette; Plant, Nick J.

    2017-01-01

    The scope of physiologically based pharmacokinetic (PBPK) modeling can be expanded by assimilation of the mechanistic models of intracellular processes from systems biology field. The genome scale metabolic networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are available. Here, we introduce GSMNs and review ongoing work on integration of PBPK, GSMNs, and metabolic gene regulation. We demonstrate example models. PMID:28782239

  7. Androgenicity in relation to body fat distribution and metabolism in 38-year-old women--the European Fat Distribution Study

    NARCIS (Netherlands)

    Seidell, J C; Cigolini, M; Charzewska, J; Ellsinger, B M; Di Biase, G; Björntorp, P; Hautvast, J.G.A.J.; Contaldo, F; Szostak, V; Scuro, L A

    1990-01-01

    We studied fat distribution and metabolic risk factors in 434 38-year old women selected from population registrars in 5 cities in different parts of Europe. In the present study we focussed on the geographical variation in serum concentrations of free testosterone and its relation to measures of

  8. Effects of low-fat milk consumption on metabolic and atherogenic biomarkers in Korean adults with the metabolic syndrome: a randomised controlled trial.

    Science.gov (United States)

    Lee, Y J; Seo, J A; Yoon, T; Seo, I; Lee, J H; Im, D; Lee, J H; Bahn, K-N; Ham, H S; Jeong, S A; Kang, T S; Ahn, J H; Kim, D H; Nam, G E; Kim, N H

    2016-08-01

    Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome. Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks. No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group. The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia. © 2016 The British Dietetic Association Ltd.

  9. MiR130b-Regulation of PPARγ Coactivator- 1α Suppresses Fat Metabolism in Goat Mammary Epithelial Cells.

    Science.gov (United States)

    Chen, Zhi; Luo, Jun; Ma, LiuAn; Wang, Hui; Cao, WenTing; Xu, HuiFei; Zhu, JiangJiang; Sun, YuTing; Li, Jun; Yao, DaWei; Kang, Kang; Gou, Deming

    2015-01-01

    Fat metabolism is a complicated process regulated by a series of factors. microRNAs (miRNAs) are a class of negative regulator of proteins and play crucial roles in many biological processes; including fat metabolism. Although there have been some researches indicating that miRNAs could influence the milk fat metabolism through targeting some factors, little is known about the effect of miRNAs on goat milk fat metabolism. Here we utilized an improved miRNA detection assay, S-Poly-(T), to profile the expression of miRNAs in the goat mammary gland in different periods, and found that miR-130b was abundantly and differentially expressed in goat mammary gland. Additionally, overexpressing miR-130b impaired adipogenesis while inhibiting miR-130b enhanced adipogenesis in goat mammary epithelial cells. Utilizing 3'-UTR assay and Western Blot analusis, the protein peroxisome proliferator-activated receptor coactivator-1α (PGC1α), a major regulator of fat metabolism, was demonstrated to be a potential target of miR-130b. Interestingly, miR-130b potently repressed PGC1α expression by targeting both the PGC1α mRNA coding and 3' untranslated regions. These findings have some insight of miR-130b in mediating adipocyte differentiation by repressing PGC1α expression and this contributes to further understanding about the functional significance of miRNAs in milk fat synthesis.

  10. Opioid receptor mu 1 gene, fat intake and obesity in adolescence.

    Science.gov (United States)

    Haghighi, A; Melka, M G; Bernard, M; Abrahamowicz, M; Leonard, G T; Richer, L; Perron, M; Veillette, S; Xu, C J; Greenwood, C M T; Dias, A; El-Sohemy, A; Gaudet, D; Paus, T; Pausova, Z

    2014-01-01

    Dietary preference for fat may increase risk for obesity. It is a complex behavior regulated in part by the amygdala, a brain structure involved in reward processing and food behavior, and modulated by genetic factors. Here, we conducted a genome-wide association study (GWAS) to search for gene loci associated with dietary intake of fat, and we tested whether these loci are also associated with adiposity and amygdala volume. We studied 598 adolescents (12-18 years) recruited from the French-Canadian founder population and genotyped them with 530 011 single-nucleotide polymorphisms. Fat intake was assessed with a 24-hour food recall. Adiposity was examined with anthropometry and bioimpedance. Amygdala volume was measured by magnetic resonance imaging. GWAS identified a locus of fat intake in the μ-opioid receptor gene (OPRM1, rs2281617, P=5.2 × 10(-6)), which encodes a receptor expressed in the brain-reward system and shown previously to modulate fat preference in animals. The minor OPRM1 allele appeared to have a 'protective' effect: it was associated with lower fat intake (by 4%) and lower body-fat mass (by ∼2 kg, P=0.02). Consistent with the possible amygdala-mediated inhibition of fat preference, this allele was additionally associated with higher amygdala volume (by 69 mm(3), P=0.02) and, in the carriers of this allele, amygdala volume correlated inversely with fat intake (P=0.02). Finally, OPRM1 was associated with fat intake in an independent sample of 490 young adults. In summary, OPRM1 may modulate dietary intake of fat and hence risk for obesity, and this effect may be modulated by subtle variations in the amygdala volume.

  11. Fatty acid translocase gene CD36 rs1527483 variant influences oral fat perception in Malaysian subjects.

    Science.gov (United States)

    Ong, Hing-Huat; Tan, Yen-Nee; Say, Yee-How

    2017-01-01

    We determined whether single nucleotide polymorphisms (SNPs; rs1761667 and rs1527483) in the fatty acid translocase CD36 gene - a receptor for fatty acids - is associated with oral fat perception (OFP) of different fat contents in custards and commercially-available foods, and obesity measures in Malaysian subjects (n=313; 118 males, 293 ethnic Chinese; 20 ethnic Indians). A 170-mm visual analogue scale was used to assess the ratings of perceived fat content, oiliness and creaminess of 0%, 2%, 6% and 10% fat content-by-weight custards and low-fat/regular versions of commercially-available milk, mayonnaise and cream crackers. Overall, the subjects managed to significantly discriminate the fat content, oiliness and creaminess between low-fat/regular versions of milk and mayonnaise. Females rated the perception of fat content and oiliness of both milks higher, but ethnicity, obesity and adiposity status did not seem to play a role in influencing most of OFP. The overall minor allele frequencies for rs1761667 and rs1527483 were 0.30 and 0.26, respectively. Females and individuals with rs1527483 TT genotype significantly perceived greater creaminess of 10% fat-by-weight custard. Also, individuals with rs1527483 TT genotype and T allele significantly perceived greater fat content of cream crackers, independent of fat concentration. rs1761667 SNP did not significantly affect OFP, except for cream crackers. Both gene variants were also not associated with obesity measures. Taken together, this study supports the notion that CD36 - specifically rs1527483, plays a role in OFP, but not in influencing obesity in Malaysian subjects. Besides, gender is an important factor for OFP, where females had higher sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring.

    Science.gov (United States)

    Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

    2017-01-01

    The mother's consumption of high-fat food can affect glucose metabolism and the hypothalamic-pituitary-adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Female rats were randomly divided into normal and high-fat diet groups and were fed in accordance with their given diets from pre-pregnancy to the end of lactation. The offspring were divided into control (NC and HFC) and stress (NS and HFS) groups based on their mothers' diet and exposure to stress in adulthood. After the two-week stress induction period was over, an intraperitoneal glucose tolerance test (IPGTT) was performed and plasma glucose and insulin levels were assessed. The pancreas was then removed for measuring insulin secretion from the isolated islets as well as glucose transporter 2 mRNA expression and protein levels. According to the results obtained, plasma corticosterone concentrations increased significantly on days 1 and 14 of the stress induction period and were lower on the last day compared to on the first day. In both the NS and HFS groups, stress reduced plasma insulin concentration in the IPGTT without changing the plasma glucose concentration, suggesting an increased insulin sensitivity in the NS and HFS groups, although more markedly in the latter. Stress reduced insulin secretion (at high glucose concentrations) and increased glucose transporter 2 mRNA and protein expression, especially in the HFS group. Mothers' high-fat diet appears to intensify the stress response by changing the programming of the neuroendocrine system in the offspring.

  13. Unraveling molecular mechanistic differences in liver metabolism between lean and fat lines of Pekin duck (Anas platyrhynchos domestica): a proteomic study.

    Science.gov (United States)

    Zheng, Aijuan; Chang, Wenhuan; Hou, Shuisheng; Zhang, Shu; Cai, Huiyi; Chen, Guilan; Lou, Ruiying; Liu, Guohua

    2014-02-26

    Duck is one of the major poultry meat sources for human consumption. To satisfy different eating habits, lean and fat strains of Pekin ducks have been developed. The objective of this study was to determine the molecular mechanistic differences in liver metabolism between two duck strains. The liver proteome of the Pekin duck lines was compared on days 1, 14, 28, and 42 posthatching using 2-DE based proteomics. There was a different abundance of 76 proteins in the livers of the two duck lines. Fat ducks strongly expressed proteins related to pathways of glycolysis, ATP synthesis, and protein catabolism, suggesting enhanced fat deposition rather than protein retention. In contrast, highly expressed proteins in lean ducks improved protein anabolism and reduced protein catabolism, resulting in an enhancement of lean meat deposition. Along with the decrease in fat deposition, the immune system of the lean duck strain may be enhanced by enhanced expression of proteins involved in stress response, immune defense, and antioxidant functions. These results indicate that selection pressure has shaped the two duck lines differently resulting in different liver metabolic capacities. These observed variations between the two strains at the molecular level are matched with physiological changes in growth performance and meat production. This information may have beneficial impacts in areas such as genetic modification through the manipulation of target proteins or genes in specific pathways to improve the efficiency of duck meat production. The objective of this study was to unravel molecular mechanistic differences in liver metabolism between lean and fat Pekin duck (Anas platyrhynchos domestica) strains. There was a different abundance of 76 proteins in the livers of the two duck lines. Enhanced protein expression in the fat ducks related to pathways of glycolysis, ATP synthesis and protein catabolism suggesting increased fat deposition rather than protein retention. In

  14. Cinnamon improves insulin sensitivity, prevents mesenteric fat accumulation, and increases glycogen synthesis in an animal model of the metabolic syndrome

    Science.gov (United States)

    In Western countries, over consumption of fat and/or refined carbohydrates are leading causes of insulin resistance, obesity, and the metabolic syndrome. Some nutritional factors, including many polyphenols, may be beneficial in counteracting insulin resistance associated with the metabolic syndrom...

  15. Comparison of the relative contributions of intra-abdominal and liver fat to components of the metabolic syndrome

    DEFF Research Database (Denmark)

    Kotronen, Anna; Yki-Järvinen, Hannele; Sevastianova, Ksenia

    2011-01-01

    Abdominally obese individuals with the metabolic syndrome often have excess fat deposition both intra-abdominally (IA) and in the liver, but the relative contribution of these two deposits to variation in components of the metabolic syndrome remains unclear. We determined the mutually independent...... were correlated (r = 0.65, P density lipoprotein (HDL) cholesterol, plasma glucose, insulin and liver enzyme concentrations, and hepatic...

  16. Metabolic syndrome: Differences for Asian Americans is in their percentage of body fat

    Directory of Open Access Journals (Sweden)

    Patricia Alpert

    2016-09-01

    Full Text Available Asian Americans are not frequently thought of as being obese or overweight yet some of the Asian American subgroups have a disproportionate risk for cardiovascular disease and type 2 diabetes mellitus. Although the standardized body mass index (BMI assessment is an adequate tool for reporting secular prevalence trends for overweight/obesity across populations, it falls short in accuracy when assessing Asian Americans. In recent years more has been written about the re-evaluation of BMI cut points for normal weight, overweight, or obese Asian Americans. Additionally, the waist circumference norm was modified to indicate a smaller waist size is a risk for metabolic syndrome. The purpose of this paper is to provide an overview of the research literature on BMI and percentage of body fat as it relates to health risk for metabolic syndrome for Asian American subgroups. Three databases were used to identify articles for this review: Google Scholar, CINHAL, and PubMed. Seven hundred twenty-six articles were initially identified as meeting the criteria; 690 articles were eliminated after a review of the article titles revealed the content did not meet the focus of this review. Of the remaining articles, 19 were eliminated after a review of the abstracts indicated they were meta-analyses, review articles, or case studies. The remaining 18 articles were included in this review. Three common themes emerged. (1 The differences in BMI and body fat percentage are evident between Asian Americans and other ethnic groups. (2 Differences in the percentage of body fat exist between Asian American subgroups, and between Asian Americans and Asian immigrants. (3 There are differences in disease development end points when comparing Asian American subgroups and Asian immigrant subgroups. There are differences in body fat distribution and body fat percentages as well as BMI compared to other ethnic groups for metabolic syndrome. There are also differences between Asian

  17. Effects of Mixed Isoenergetic Meals on Fat and Carbohydrate Metabolism during Exercise in Older Men

    Directory of Open Access Journals (Sweden)

    Minoo Bassami

    2011-01-01

    Full Text Available The present study was designed to investigate the effects of four different meals on fat and CHO metabolism during subsequent exercise in elderly males. Eight healthy males (age: 63.3 ± 5.2 years reported to the physiology laboratory on four separate occasions, each of which was allocated for the performance of a 30-minute exercise on a cycle ergometer at 60% ̇VO2max after having normal (N, high fat (HF, high carbohydrate high glycaemic index (HGI and high carbohydrate low glycaemic index (LGI meals. Fat oxidation during exercise after the meals (HF=0.26±0.04 g/min; N=0.21±0.04 g/min; HGI=0.22±0.03 g/min; LGI=0.19±0.03 g/min was not significant (>.05, and neither were the rates of carbohydrate oxidation (N=1.79±0.28, HF=1.58±0.22, HGI=1.68±0.22, and LGI=1.77±0.21 g/m. NEFA concentration increased after HF (<.05 but decreased after HGI and LGI (<.05. Glucose concentration decreased as a result of exercise after HF, and LGI (<.05 whereas insulin concentration decreased significantly during exercise after N, HF, and HGI (<.05. It can be concluded that, in elderly males, feeding isoenergetic meals containing different proportions of carbohydrate and fat do not significantly alter oxidation of fat and CHO during exercise in spite of changes in some circulating metabolites.

  18. Genome-wide examination of chlorophyll metabolic genes in maize ...

    African Journals Online (AJOL)

    Chlorophyll (Chl) is the key pigment involved in photosynthesis. Analysis of the expression pattern of Chl metabolic genes will contribute to our understanding of photosynthesis. Also, the genes coding for Chl metabolism are ideal targets for revealing the evolution relationships of photosynthetic organisms. In this study, we ...

  19. Genome-wide examination of chlorophyll metabolic genes in maize ...

    African Journals Online (AJOL)

    Jane

    2011-06-22

    Jun 22, 2011 ... Chlorophyll (Chl) is the key pigment involved in photosynthesis. Analysis of the expression pattern of. Chl metabolic genes will contribute to our understanding of photosynthesis. Also, the genes coding for. Chl metabolism are ideal targets for revealing the evolution relationships of photosynthetic organisms ...

  20. Chitin Oligosaccharide Modulates Gut Microbiota and Attenuates High-Fat-Diet-Induced Metabolic Syndrome in Mice

    Directory of Open Access Journals (Sweden)

    Junping Zheng

    2018-02-01

    Full Text Available Gut microbiota has been proved to be an indispensable link between nutrient excess and metabolic syndrome, and chitin oligosaccharide (NACOS has displayed therapeutic effects on multiple diseases such as cancer and gastritis. In this study, we aim to confirm whether NACOS can ameliorate high-fat diet (HFD-induced metabolic syndrome by rebuilding the structure of the gut microbiota community. Male C57BL/6J mice fed with HFD were treated with NACOS (1 mg/mL in drinking water for five months. The results indicate that NACOS improved glucose metabolic disorder in HFD-fed mice and suppressed mRNA expression of the protein regulators related to lipogenesis, gluconeogenesis, adipocyte differentiation, and inflammation in adipose tissues. Additionally, NACOS inhibited the destruction of the gut barrier in HFD-treated mice. Furthermore, 16S ribosome RNA sequencing of fecal samples demonstrates that NACOS promoted the growth of beneficial intestinal bacteria remarkably and decreased the abundance of inflammogenic taxa. In summary, NACOS partly rebuilt the microbial community and improved the metabolic syndrome of HFD-fed mice. These data confirm the preventive effects of NACOS on nutrient excess-related metabolic diseases.

  1. [The role of cytochrome P450 in nonalcoholic fatty liver induced by high-fat diet: a gene expression profile analysis].

    Science.gov (United States)

    Liu, Y; Cheng, F; Luo, Y X; Hu, P; Ren, H; Peng, M L

    2017-04-20

    Objective: To clarify the role of cytochrome P450 in nonalcoholic fatty liver disease (NAFLD) by RNA-Seq and bioinformatics analysis. Methods: A total of 20 male C57BL/6 mice were used. Ten mice were fed with high-fat diet (D12492, 60% kcal fat) for 16 weeks to establish a mouse model of NAFLD, and the other 10 mice were fed with low-fat diet (D12450B, 10% kcal fat) as control group. At the end of the experiment, the body weight, liver weight, and hepatic triglyceride (TG) content were measured. Meanwhile, HE staining and RNA-Seq analysis were performed for the liver tissues. The differentially expressed genes were screened out and subjected to bioinformatics analysis, including KEGG and GO BP enrichment analyses and interaction network analysis. Comparison of means between the two groups was made using t-test. Results: Compared with the control group, the mice in the model group were obviously obese, with significantly increased body weight (41.41 ± 6.01 g vs 28.78 ± 1.79 g, t = 6.04, P liver weight (1.38 ± 0.30 g vs 1.08 ± 0.10 g, t = 2.89, P fatty acid metabolism, arachidonic acid metabolism, and the PPAR signaling pathway. An interaction network was constructed with 30 nodes, and CYP2E1 and CYP2C70 were identified as key nodes. RT-PCR validation results showed that the expression changes of CYP450 subtypes and lipid metabolism-related genes were consistent with the findings of sequencing. Conclusion: The CYP450 family plays a vital role in the pathogenesis of fatty liver by regulating lipid metabolism-related pathways, including oxidative stress, arachidonic acid metabolism, steroid hormone metabolism , and fatty acid metabolism.

  2. Effect of low temperature on metabolism of rat liver slices and epididymal fat pads.

    Science.gov (United States)

    Hillyard, L. A.; Entenman, C.

    1973-01-01

    Study of low temperature effects on the metabolism of radioisotope-tagged glucose and palmitate in rat liver slices and epididymal fat pads. The obtained data suggest that the oxidative capacity of rat liver and adipose tissue is maintained at low temperatures to a greater degree than the synthetic capacity. It was concluded that sufficient energy can be produced at 17 C for maintenance of essential tissue functions by these two tissues but that the energy requirements may not be met at 7 C.

  3. Cut-off value of body fat in association with metabolic syndrome in Thai peri- and postmenopausal women.

    Science.gov (United States)

    Bintvihok, W; Chaikittisilpa, S; Panyakamlerd, K; Jaisamrarn, U; Taechakraichana, N

    2013-06-01

    Pathophysiologic changes during the menopause transition may contribute to the risk of metabolic syndrome (MetS). Body fat composition, particularly visceral fat, is highly associated with increased insulin resistance, abnormal carbohydrate metabolism and high blood pressure. We purposefully wished to determine the optimal cut-off values of body fat composition, including visceral fat, in order to predict MetS and to assess the prevalence of MetS in peri- and postmenopausal women. This cross-sectional study was conducted in a population-based, prospective cohort at the Menopause and Gynecology clinics, King Chulalongkorn Memorial Hospital. Body fat percentage and visceral fat rating were measured by a bioelectrical impedance analyzer (Tanita SC 330). MetS was diagnosed using the Harmonizing criteria of A Joint Interim Statement of IDF/NHLBI/AHA/WHF/IAS/IASO 2009. Receiver operating characteristic analyses were performed to determine the optimal cut-off values of body fat, visceral fat, waist circumference and body mass index to identify peri- and postmenopausal women at risk of MetS. Ninety-two perimenopausal and 446 postmenopausal women aged 40-60 years were recruited for the analyses. The optimal cut-off values for body fat percentage, visceral fat rating, waist circumference and body mass index for identifying women at risk of MetS were 34%, 7, 88 cm and 24 kg/m(2), respectively. The prevalence of MetS in this study was 27.9%. The optimal cut-off values to predict MetS of body fat percentage, visceral fat and waist circumference were established. Using the Harmonizing 2009 criteria, we found that approximately one out of four peri- and postmenopausal women in this study had MetS.

  4. High fat diet and in utero exposure to maternal obesity disrupts circadian rhythm and leads to metabolic programming of liver in rat offspring.

    Directory of Open Access Journals (Sweden)

    Sarah J Borengasser

    Full Text Available The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosis, and lipogenic gene expression in the liver at weaning. However, the precise underlying mechanisms leading to metabolic dysregulation in the offspring remains unclear. Using a rat model of overfeeding-induced obesity, we previously demonstrated that exposure to maternal obesity from pre-conception to birth, is sufficient to program increased obesity risk in the offspring. Offspring of obese rat dams gain greater body weight and fat mass when fed high fat diet (HFD as compared to lean dam. Since, disruptions of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver, we examined the hypothesis that maternal obesity leads to perturbations of core clock components and thus energy metabolism in offspring liver. Offspring from lean and obese dams were examined at post-natal day 35, following a short (2 wk HFD challenge. Hepatic mRNA expression of circadian (CLOCK, BMAL1, REV-ERBα, CRY, PER and metabolic (PPARα, SIRT1 genes were strongly suppressed in offspring exposed to both maternal obesity and HFD. Using a mathematical model, we identified two distinct biological mechanisms that modulate PPARα mRNA expression: i decreased mRNA synthesis rates; and ii increased non-specific mRNA degradation rate. Moreover, our findings demonstrate that changes in PPARα transcription were associated with epigenomic alterations in H3K4me3 and H3K27me3 histone marks near the PPARα transcription start site. Our findings indicated that offspring from obese rat dams have detrimental alternations to circadian machinery that may contribute to impaired liver metabolism in response to HFD, specifically via reduced PPAR

  5. INFLUENCE OF GENETIC POLYMORPHISM IN FABP3 AND LEPR GENES ON INTRAMUSCULAR FAT CONTENT IN PIG CARCASSES

    Directory of Open Access Journals (Sweden)

    Kristina Budimir

    2014-06-01

    Full Text Available Intensive production conditions, selection directed to increase the percentage of muscle tissue in carcasses and consumer demand have led to a reduction of intramuscular fat content in pig carcasses. Intramuscular fat is a factor affecting the flavor, juiciness and tenderness of pork meat. FABP protein family causes the differences in the content of intramuscular fat in different pig breeds. FABP3 and LEPR gene are candidate genes for intramuscular fat content and their polymorphisms explain the variability that can occur in different pig breeds. The aim of this paper is to demonstrate the influence of genes on different intramuscular fat content in pig carcasses due to pigs genotype.

  6. Modulation of Microbiota-Gut-Brain Axis by Berberine Resulting in Improved Metabolic Status in High-Fat Diet-Fed Rats

    Directory of Open Access Journals (Sweden)

    Honglin Sun

    2016-11-01

    Full Text Available Objective: To investigate whether or not berberine could improve metabolic status of high-fat-fed rats through modulation of microbiota-gut-brain axis. Methods: Berberine was administered on high-fat-fed Sprague-Dawley rats. Brain-gut hormones were detected, and changes of gut microbiota were analyzed by 16S rRNA gene sequencing. Results: Berberine could reduce weight gain and lipolysis in the high-fat diet-fed group. Moreover, trends of ameliorated insulin resistance and decreased endogenous glucose production were observed. In addition, the microbiota-gut-brain axis was found to be modulated, including structural and diversity changes of microbiota, elevated serum glucagon-like peptide-1 and neuropeptide Y level, decreased orexin A level, up-regulated glucagon-like peptide-1 receptor mRNA level as well as ultra-structural improvement of the hypothalamus. Conclusion: Taken together, our findings suggest that berberine improved metabolic disorders induced by high-fat diet through modulation of the microbiota-gut-brain axis.

  7. Modulation of Microbiota-Gut-Brain Axis by Berberine Resulting in Improved Metabolic Status in High-Fat Diet-Fed Rats.

    Science.gov (United States)

    Sun, Honglin; Wang, Ningjian; Cang, Zhen; Zhu, Chaoxia; Zhao, Li; Nie, Xiaomin; Cheng, Jing; Xia, Fangzhen; Zhai, Hualing; Lu, Yingli

    2016-01-01

    To investigate whether or not berberine could improve metabolic status of high-fat-fed rats through modulation of microbiota-gut-brain axis. Berberine was administered on high-fat-fed Sprague-Dawley rats. Brain-gut hormones were detected, and changes of gut microbiota were analyzed by 16S rRNA gene sequencing. Berberine could reduce weight gain and lipolysis in the high-fat diet-fed group. Moreover, trends of ameliorated insulin resistance and decreased endogenous glucose production were observed. In addition, the microbiota-gut-brain axis was found to be modulated, including structural and diversity changes of microbiota, elevated serum glucagon-like peptide-1 and neuropeptide Y level, decreased orexin A level, up-regulated glucagon-like peptide-1 receptor mRNA level as well as ultra-structural improvement of the hypothalamus. Taken together, our findings suggest that berberine improved metabolic disorders induced by high-fat diet through modulation of the microbiota-gut-brain axis. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

  8. Effect of testosterone deficiency on cholesterol metabolism in pigs fed a high-fat and high-cholesterol diet.

    Science.gov (United States)

    Cai, Zhaowei; Xi, Haitao; Pan, Yongming; Jiang, Xiaoling; Chen, Liang; Cai, Yueqin; Zhu, Keyan; Chen, Cheng; Xu, Xiaoping; Chen, Minli

    2015-03-07

    Testosterone deficiency is associated with increased serum cholesterol levels. However, how testosterone deficiency precisely affects cholesterol metabolism remains unclear. Therefore, in the current study, we examined the effect of testosterone deficiency on cholesterol metabolism and liver gene expression in pigs fed a high-fat and high-cholesterol (HFC) diet. Sexually mature male miniature pigs (6-7 months old) were randomly divided into 3 groups as follows: intact male pigs fed an HFC diet (IM+HFC), castrated male pigs fed an HFC diet (CM+HFC), and castrated pigs with testosterone replacement fed an HFC diet (CM+HFC+T). Serum testosterone levels and lipid profiles were measured, and gene expression levels associated with hepatic cholesterol metabolism were determined. Furthermore, total hepatic cholesterol contents and the activities of enzymes mediating hepatic cholesterol metabolism were measured. Serum testosterone levels were significantly decreased in CM+HFC pigs, and testosterone replacement attenuated castration-induced testosterone deficiency. Castration significantly increased the serum levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as hepatic lipid contents in pigs fed an HFC diet. Compared with IM+HFC and CM+HFC+T pigs, low-density lipoprotein receptor (LDLR) mRNA expression and protein levels were significantly decreased in the livers of CM+HFC pigs. In contrast, we found that compared with IM+HFC pigs, hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and serum PCSK9 protein levels were significantly increased in CM+HFC pigs. Moreover, testosterone treatment reversed the increase in PCSK9 expression in CM+HFC pigs. However, neither castration nor testosterone replacement affected the expression of the other hepatic genes that were tested. This study demonstrated that castration-induced testosterone deficiency caused severe hypercholesterolemia in pigs fed an HFC diet; furthermore, these

  9. Fat and carbohydrates in the diet: Its metabolic contribution to obesity in Chilean women. Highlights and achievements

    International Nuclear Information System (INIS)

    Diaz, E.

    2002-01-01

    The n6 and n3 fatty acids differentially affect the fat oxidation rate, enzyme activity and gene expression. This way, the type of fatty acids ingested can modulate the fat balance. It could modify the lipid content in insulin sensitivity tissues and decrease the risk for insulin resistance in predisposed subjects

  10. Ananas comosus L. Leaf Phenols and p-Coumaric Acid Regulate Liver Fat Metabolism by Upregulating CPT-1 Expression

    Directory of Open Access Journals (Sweden)

    Weidong Xie

    2014-01-01

    Full Text Available In this study, we aimed to investigate the effect and action mechanisms of pineapple leaf phenols (PLPs on liver fat metabolism in high-fat diet-fed mice. Results show that PLP significantly reduced abdominal fat and liver lipid accumulation in high-fat diet-fed mice. The effects of PLP were comparable with those of FB. Furthermore, at the protein level, PLP upregulated the expression of carnitine palmitoyltransferase 1 (CPT-1, whereas FB had no effects on CPT-1 compared with the HFD controls. Regarding mRNA expression, PLP mainly promoted the expression of CPT-1, PGC1a, UCP-1, and AMPK in the mitochondria, whereas FB mostly enhanced the expression of Ech1, Acox1, Acaa1, and Ehhadh in peroxisomes. PLP seemed to enhance fat metabolism in the mitochondria, whereas FB mainly exerted the effect in peroxisomes. In addition, p-coumaric acid (CA, one of the main components from PLP, significantly inhibited fat accumulation in oleic acid-induced HepG2 cells. CA also significantly upregulated CPT-1 mRNA and protein expressions in HepG2 cells. We, firstly, found that PLP enhanced liver fat metabolism by upregulating CPT-1 expression in the mitochondria and might be promising in treatment of fatty liver diseases as alternative natural products. CA may be one of the active components of PLP.

  11. Evaluation of Beneficial Metabolic Effects of Berries in High-Fat Fed C57BL/6J Mice

    Directory of Open Access Journals (Sweden)

    Lovisa Heyman

    2014-01-01

    Full Text Available Objective. The aim of the study was to screen eight species of berries for their ability to prevent obesity and metabolic abnormalities associated with type 2 diabetes. Methods. C57BL/6J mice were assigned the following diets for 13 weeks: low-fat diet, high-fat diet or high-fat diet supplemented (20% with lingonberry, blackcurrant, bilberry, raspberry, açai, crowberry, prune or blackberry. Results. The groups receiving a high-fat diet supplemented with lingonberries, blackcurrants, raspberries or bilberries gained less weight and had lower fasting insulin levels than the control group receiving high-fat diet without berries. Lingonberries, and also blackcurrants and bilberries, significantly decreased body fat content, hepatic lipid accumulation, and plasma levels of the inflammatory marker PAI-1, as well as mediated positive effects on glucose homeostasis. The group receiving açai displayed increased weight gain and developed large, steatotic livers. Quercetin glycosides were detected in the lingonberry and the blackcurrant diets. Conclusion. Lingonberries were shown to fully or partially prevent the detrimental metabolic effects induced by high-fat diet. Blackcurrants and bilberries had similar properties, but to a lower degree. We propose that the beneficial metabolic effects of lingonberries could be useful in preventing obesity and related disorders.

  12. Nopal (Opuntia ficus indica) protects from metabolic endotoxemia by modifying gut microbiota in obese rats fed high fat/sucrose diet.

    Science.gov (United States)

    Sánchez-Tapia, Mónica; Aguilar-López, Miriam; Pérez-Cruz, Claudia; Pichardo-Ontiveros, Edgar; Wang, Mei; Donovan, Sharon M; Tovar, Armando R; Torres, Nimbe

    2017-07-05

    Current efforts are directed to reducing the gut dysbiosis and inflammation produced by obesity. The purpose of this study was to investigate whether consuming nopal, a vegetable rich in dietary fibre, vitamin C, and polyphenols can reduce the metabolic consequences of obesity by modifying the gut microbiota and preventing metabolic endotoxemia in rats fed a high fat and sucrose diet. With this aim, rats were fed a high fat diet with 5% sucrose in the drinking water (HFS) for 7 months and then were fed for 1 month with HFS + 5% nopal (HFS + N). The composition of gut microbiota was assessed by sequencing the 16S rRNA gene. Nopal modified gut microbiota and increased intestinal occludin-1 in the HFS + N group. This was associated with a decrease in metabolic endotoxemia, glucose insulinotropic peptide, glucose intolerance, lipogenesis, and metabolic inflexibility. These changes were accompanied by reduced hepatic steatosis and oxidative stress in adipose tissue and brain, and improved cognitive function, associated with an increase in B. fragilis. This study supports the use of nopal as a functional food and prebiotic for its ability to modify gut microbiota and to reduce metabolic endotoxemia and other obesity-related biochemical abnormalities.

  13. Circulating cortisol-associated signature of glucocorticoid-related gene expression in subcutaneous fat of obese subjects.

    Science.gov (United States)

    Pavlatou, Maria G; Vickers, Kasey C; Varma, Sudhir; Malek, Rana; Sampson, Maureen; Remaley, Alan T; Gold, Philip W; Skarulis, Monica C; Kino, Tomoshige

    2013-05-01

    Serum cortisol concentrations fluctuate in a circadian fashion, and glucocorticoids exert strong effects on adipose tissue and induce obesity through the glucocorticoid receptor. To examine the impact of physiologic levels of circulating cortisol on subcutaneous adipose tissue, 25 overweight and obese subjects were employed, and their serum levels of morning (AM) and evening (PM) cortisol, AM/PM cortisol ratios, and 24-h urinary-free cortisol (UFC) were compared with their clinical parameters, serum cytokine levels, and mRNA expression of 93 receptor action-regulating and 93 glucocorticoid-responsive genes in abdominal subcutaneous fat. AM cortisol levels did not correlate with mRNA expression of the all genes examined, whereas PM cortisol levels, AM/PM cortisol ratios, and 24-h UFC were associated with distinct sets of these genes. Body mass index did not significantly correlate with the four cortisol parameters employed. These results suggest that physiologic levels of AM serum cortisol do not solely represent biological effects of circulating cortisol on the expression of glucocorticoid-related genes in subcutaneous adipose tissue, whereas PM levels, amplitude, and net amounts of the diurnally fluctuating serum cortisol have distinct effects. Through the genes identified in this study, glucocorticoids appear to influence intermediary metabolism, energy balance, inflammation, and local circadian rythmicity in subcutaneous fat. Our results may also explain in part the development of metabolic abnormality and obesity in subjects under stress or patients with melancholic/atypical depression who demonstrate elevated levels of PM serum cortisol. Copyright © 2013 The Obesity Society.

  14. Association of Vitamin E Levels with Metabolic Syndrome, and MRI-Derived Body Fat Volumes and Liver Fat Content

    Directory of Open Access Journals (Sweden)

    Sabina Waniek

    2017-10-01

    Full Text Available We aimed to relate circulating α- and γ-tocopherol levels to a broad spectrum of adiposityrelated traits in a cross-sectional Northern German study. Anthropometric measures were obtained, and adipose tissue volumes and liver fat were quantified by magnetic resonance imaging in 641 individuals (mean age 61 years; 40.6% women. Concentrations of α- and γ-tocopherol were measured using high performance liquid chromatography. Multivariable-adjusted linear and logistic regression were used to assess associations of circulating α- and γ-tocopherol/cholesterol ratio levels with visceral (VAT and subcutaneous adipose tissue (SAT, liver signal intensity (LSI, fatty liver disease (FLD, metabolic syndrome (MetS, and its individual components. The α- tocopherol/cholesterol ratio was positively associated with VAT (β scaled by interquartile range (IQR: 0.036; 95%Confidence Interval (CI: 0.0003; 0.071 and MetS (Odds Ratio (OR: 1.83; 95% CI: 1.21–2.76 for 3rd vs. 1st tertile, and the γ-tocopherol/cholesterol ratio was positively associated with VAT (β scaled by IQR: 0.066; 95% CI: 0.027; 0.104, SAT (β scaled by IQR: 0.048; 95% CI: 0.010; 0.087 and MetS (OR: 1.87; 95% CI: 1.23–2.84 for 3rd vs. 1st tertile. α- and γ-tocopherol levels were positively associated with high triglycerides and low high density lipoprotein cholesterol levels (all Ptrend < 0.05. No association of α- and γ-tocopherol/cholesterol ratio with LSI/FLD was observed. Circulating vitamin E levels displayed strong associations with VAT and MetS. These observations lay the ground for further investigation in longitudinal studies.

  15. Association of fat mass and obesity-associated gene variant with lifestyle factors and body fat in Indian Children

    Directory of Open Access Journals (Sweden)

    Lavanya S Parthasarthy

    2017-01-01

    Full Text Available Context: Common intronic variants of the fat mass and obesity-associated (FTO gene have been associated with obesity-related traits in humans. Aims: (1 The aim of this study is to study the distribution of FTO gene variants across different body mass index (BMI categories and (2 to explore the association between FTO gene variants and lifestyle factors in obese and normal weight Indian children. Subjects and Methods: Fifty-six children (26 boys, mean age 10.3 ± 2.2 years were studied. Height, weight, and waist and hip circumference were measured. Physical activity (questionnaire and food intake (food frequency questionnaire were assessed. Body fat percentage (%BF was measured by dual-energy X-ray absorptiometry. FTO allelic variants at rs9939609 site were detected by SYBR Green Amplification Refractory Mutation System real-time polymerase chain reaction using allele-specific primers. Generalized linear model was used to investigate the simultaneous influence of genetic and lifestyle factors on %BF. Results: Mean height, weight, and BMI of normal and obese children were 130.6 ± 7.1 versus 143.2 ± 15.6, 24.0 ± 5.2 versus 53.1 ± 15.8, and 13.9 ± 2.1 versus 25.3 ± 3.2, respectively. The frequency of AA allele was 57% among obese children and 35% in normal weight children. Children with the AA allele who were obese had least physical activity, whereas children with AT allele and obesity had the highest intake of calories when compared to children who had AT allele and were normal. %BF was positively associated with AA alleles and junk food intake and negatively with healthy food intake and moderate physical activity. Conclusions: Healthy lifestyle with high physical activity and diet low in calories and fat may help in modifying the risk imposed by FTO variants in children.

  16. Coenzyme Q Metabolism Is Disturbed in High Fat Diet-Induced Non Alcoholic Fatty Liver Disease in Rats

    Directory of Open Access Journals (Sweden)

    Kathleen M Botham

    2012-02-01

    Full Text Available Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD, the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control or a high fat diet (57% metabolizable energy as fat for 18 weeks. The concentrations of total (reduced + oxidized CoQ9 were increased by > 2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.

  17. Effects of Fortunella margarita fruit extract on metabolic disorders in high-fat diet-induced obese C57BL/6 mice.

    Science.gov (United States)

    Tan, Si; Li, Mingxia; Ding, Xiaobo; Fan, Shengjie; Guo, Lu; Gu, Ming; Zhang, Yu; Feng, Li; Jiang, Dong; Li, Yiming; Xi, Wanpeng; Huang, Cheng; Zhou, Zhiqin

    2014-01-01

    Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle) fruit extract (FME) on high-fat diet-induced C57BL/6 obese mice. The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow), high-fat diet (HF), and high-fat diet with 1% (w/w) extract of kumquat (HF+FME) for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay. In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC), serum low density lipoprotein cholesterol (LDL-c) levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG), serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes. Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances.

  18. EcoCyc: Enyclopedia of Escherichia coli Genes and Metabolism.

    Science.gov (United States)

    Karp, P D; Riley, M; Paley, S M; Pellegrini-Toole, A; Krummenacker, M

    1997-01-01

    The Encyclopedia of Genes and Metabolism (EcoCyc) is a database that combines information about the genome and the intermediary metabolism of Escherichia coli. It describes 2970 genes of E.coli, 547 enzymes encoded by these genes, 702 metabolic reactions that occur in E.coli and the organization of these reactions into 107 metabolic pathways. The EcoCyc graphical user interface allows scientists to query and explore the EcoCyc database using visualization tools such as genomic-map browsers and automatic layouts of metabolic pathways. EcoCyc spans the space from sequence to function to allow scientists to investigate an unusually broad range of questions. EcoCyc can be thought of as both an electronic review article because of its copious references to the primary literature, and as an in silicio model of E.coli metabolism that can be probed and analyzed through computational means.

  19. Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.

    Science.gov (United States)

    Shabalina, Irina G; Kalinovich, Anastasia V; Cannon, Barbara; Nedergaard, Jan

    2016-05-01

    The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged.

  20. Role and metabolism of free leucine in skeletal muscle in protein sparing action of dietary carbohydrate and fat

    International Nuclear Information System (INIS)

    Nakano, Kiwao; Ishikawa, Tamotsu

    1977-01-01

    Feeding rats with either a carbohydrate meal or a fat meal to the previously fasted rats caused significant decrease in urinary output of urea and total nitrogen. The content of free leucine in skeletal muscle decreased in the rats fed either a carbohydrate meal or a fat meal. Feeding of either a carbohydrate meal or a fat meal stimulated incorporation of L-leucine-1- 14 C into protein fraction of skeletal muscle and reduced its oxidation to 14 CO 2 . These results suggest that the metabolism of leucine is under nutritional regulation and that the decrease in content of free leucine in skeletal muscle might be caused by enhanced reutilization of leucine into protein by the feeding of a carbohydrate meal or a fat meal. The role of free leucine in skeletal muscle as a regulator of protein turnover in the tissue are discussed in relation to the metabolism of this branched chain amino acid. (auth.)

  1. Effects of unextruded and extruded cranberry pomace on selected metabolic parameters in high-fat diet fed rats.

    Science.gov (United States)

    Bajerska, Joanna; Chmurzynska, Agata; Mildner-Szkudlarz, Sylwia; Drzymała-Czyż, Sławomira; Górnaś, Paweł; Waśkiewicz, Agnieszka; Muzsik, Agata; Podgórski, Tomasz; Nowaczyk, Paulina; Woźniewicz, Małgorzata

    2018-01-01

    The effects of un-extruded (UCP) and extruded cranberry pomace (ECP) on fecal fat excretion, liver index, lipid and carbohydrate metabolism, and inhibition of oxidative stress due to a high-fat diet (HFD) in rats were studied. The Wistar rats for 8 weeks received one of the four diets: (1) control (modified the American Institute of Nutrition: AIN based diet containing 7% fat), (2) HFD (AIN based diet containing 30% fat), (3) HFD with 3% un-extruded (UCP) and (4) HFD with 3% (ECP). Both UCP and ECP significantly improved the plasma antioxidant capacity and decreased lipid per- oxidation in rats fed a HFD. However, only the addition of 3% UCP into the HFD significantly increased the fecal lipid excretion and considerably decreased serum triglycerides level in rats. Further investigation is needed to determine the role of an individual components present in UCP and ECP in the improvement of metabolic conditions observed in the current study.

  2. Targeting gene expression to the female larval fat body of transgenic Aedes aegypti mosquitoes.

    Science.gov (United States)

    Totten, D C; Vuong, M; Litvinova, O V; Jinwal, U K; Gulia-Nuss, M; Harrell, R A; Beneš, H

    2013-02-01

    As the fat body is a critical tissue for mosquito development, metamorphosis, immune and reproductive system function, the characterization of regulatory modules targeting gene expression to the female mosquito fat body at distinct life stages is much needed for multiple, varied strategies for controlling vector-borne diseases such as dengue and malaria. The hexameric storage protein, Hexamerin-1.2, of the mosquito Aedes atropalpus is female-specific and uniquely expressed in the fat body of fourth instar larvae and young adults. We have identified in the Hex-1.2 gene, a short regulatory module that directs female-, tissue-, and stage-specific lacZ reporter gene expression using a heterologous promoter in transgenic lines of the dengue vector Aedes aegypti. Male transgenic larvae and pupae of one line expressed no Escherichia coli β-galactosidase or transgene product; in two other lines reporter gene activity was highly female-biased. All transgenic lines expressed the reporter only in the fat body; however, lacZ mRNA levels were no different in males and females at any stage examined, suggesting that the gene regulatory module drives female-specific expression by post-transcriptional regulation in the heterologous mosquito. This regulatory element from the Hex-1.2 gene thus provides a new molecular tool for transgenic mosquito control as well as functional genetic analysis in aedine mosquitoes. © 2012 Royal Entomological Society.

  3. Lipoic acid increases the expression of genes involved in bone formation in mice fed a high-fat diet.

    Science.gov (United States)

    Xiao, Ying; Cui, Jue; Shi, Yonghui; Le, Guowei

    2011-04-01

    Antioxidant lipoic acid (LA) has been reported to have a potential prophylactic effect on bone loss induced by high-fat diet (HFD). The aim of this work was to examine the hypothesis that LA decreases bone resorption-related gene expression and increases bone formation-related gene expression in HFD-fed mice, preventing a shift in the bone metabolism balance toward resorption. Male C57BL/6 mice were fed a normal diet, HFD, or HFD plus 0.1% LA for 12 weeks. The bone metabolism-related genes differentially expressed between mice fed HFD and those fed HFD supplemented with LA were identified through complementary DNA microarray. The supplemental LA significantly increased bone mineral density and bone antioxidant capacity in mice fed HFD (P LA induced the decreased expression of genes associated with bone resorption, such as Mmp9 (1.9-fold) and Ctsk (2.3-fold), and increased those genes associated with bone formation, such as Col1a1 (1.3-fold) and Alp1 (1.5-fold). Furthermore, LA upregulated many genes involved in the Igf signaling pathway, such as Igf-1 (increased 1.7-fold), and downregulated genes involved in the p53 apoptotic pathway, such as p53 (decreased 2.3-fold), thus attenuating the HFD-induced inhibition of bone formation. Lipoic acid induced upregulation of Il12a (2.1-fold) and downregulation of Tgfbr1 (4.3-fold) and Il17a (11.3-fold), which may reduce bone resorption. In summary, LA supplementation during HFD could affect bone density, altering gene expression. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Walker Mark

    2010-11-01

    Full Text Available Abstract Background Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity. Methods This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m2 recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained. Results Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32] and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86] than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]. A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]. Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance. Conclusion A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that

  5. Effects of puerarin on lipid accumulation and metabolism in high-fat diet-fed mice.

    Directory of Open Access Journals (Sweden)

    Guodong Zheng

    Full Text Available In order to investigate the mechanisms by which puerarin from kudzu root extract regulates lipid metabolism, fifty mice were randomly assigned to five groups: normal diet, high-fat diet (HFD, and HFD containing 0.2%, 0.4% or 0.8% puerarin for 12 weeks. Body weight, intraperitioneal adipose tissue (IPAT weight, serum biochemical parameters, and hepatic and feces lipids were measured. Activity and mRNA and protein expressions of hepatic lipid metabolism-related enzymes were analyzed. Compared with HFD, 0.4% and 0.8% puerarin significantly decreased body and IPAT weight. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, triglycerides and leptin in mice fed the 0.4% and 0.8% puerarin diets compared with HFD. Fatty acid synthase activity was suppressed in mice fed the 0.4% and 0.8% puerarin diets, while the activities of AMP-activated protein kinase (AMPK, carnitine acyltransferase (CAT and hormone-sensitive lipase (HSL were increased. mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ 2 was down-regulated in liver of mice fed the 0.8% diet compared with HFD, while mRNA expression of CAT and HSL was considerably up-regulated by 0.4% and 0.8% puerarin diets. The protein expression of PPARγ2 in liver was decreased and those of p-AMPK, HSL and p-HSL were increased in mice fed 0.4% and 0.8% puerarin diets. These results suggest that > 0.4% puerarin influenced the activity, mRNA and protein levels of hepatic lipid metabolism-related enzymes, decreasing serum and liver lipids, body weight gain and fat accumulation. Puerarin might be beneficial to prevent lifestyle-related diseases.

  6. Feeding fat from distillers dried grains with solubles to dairy heifers: II. Effects on metabolic profile.

    Science.gov (United States)

    Anderson, J L; Kalscheur, K F; Clapper, J A; Perry, G A; Keisler, D H; Garcia, A D; Schingoethe, D J

    2015-08-01

    The objective of this study was to determine if increased dietary fat from dried distillers grains with solubles (DDGS) in diets of growing heifers affected metabolic profile, plasma fatty acid profile, and reproductive maturation. Thirty-three Holstein heifers (133±18 d of age) were used in a 24-wk randomized complete block design with 3 treatment diets. Treatment diets were (1) control (CON) containing ground corn (15.9% of DM) and soybean products (17.9%), (2) low-fat (LFDG) containing low-fat DDGS (21.9%) and ground corn (11.9%), or (3) high-fat (HFDG) with traditional DDGS (33.8%). Diets were isonitrogenous and isocaloric, but the HFDG diet was formulated to contain 4.8% fat compared with 2.8% in the CON and LFDG diets. All 3 diets were limit-fed to 2.45% of body weight on a dry matter basis, and resulted in a mean average daily gain of 0.96kg/d across treatments. Every 4wk, jugular blood was collected for analysis of metabolites and metabolic hormones. During wk20 of the feeding period, blood samples were collected for analysis of plasma fatty acid profiles. When heifers weighed between 200 and 300kg of body weight, coccygeal blood samples were taken twice weekly for analysis of progesterone to determine if puberty had been reached. Plasma concentrations of nonesterified fatty acids were similar among treatments and consistent over the duration of the study. Plasma concentrations of β-hydroxybutyrate, insulin, insulin-like growth factor-1, and leptin were similar among heifers fed each treatment diet, but increased over the duration of the feeding period. Serum concentrations of glucose tended to be less in heifers fed HFDG compared with heifers fed the CON diet. Glucose concentrations fluctuated throughout the feeding period, but no treatment by time interactions were noted. Plasma urea N concentrations were less in heifers fed LFDG compared with heifers fed HFDG and CON diets. The concentrations of plasma urea N increased over the duration of the feeding

  7. Association of porcine UCP3 gene polymorphisms with fatness traits ...

    African Journals Online (AJOL)

    Administrator

    2011-04-25

    Apr 25, 2011 ... Pietrain×Jinhua F2; LEA, loin eye area; WHC, water holding capacity. The common effect of all three uncoupling proteins is uncoupling oxidative phosphorylation by mediating proton leak (Gong et al., 1997). Recent studies explored the role of UCP3 in mitochondrial fatty acid metabolism. (Nedergaard and ...

  8. Parametric recursive system identification and self-adaptive modeling of the human energy metabolism for adaptive control of fat weight.

    Science.gov (United States)

    Őri, Zsolt P

    2017-05-01

    A mathematical model has been developed to facilitate indirect measurements of difficult to measure variables of the human energy metabolism on a daily basis. The model performs recursive system identification of the parameters of the metabolic model of the human energy metabolism using the law of conservation of energy and principle of indirect calorimetry. Self-adaptive models of the utilized energy intake prediction, macronutrient oxidation rates, and daily body composition changes were created utilizing Kalman filter and the nominal trajectory methods. The accuracy of the models was tested in a simulation study utilizing data from the Minnesota starvation and overfeeding study. With biweekly macronutrient intake measurements, the average prediction error of the utilized carbohydrate intake was -23.2 ± 53.8 kcal/day, fat intake was 11.0 ± 72.3 kcal/day, and protein was 3.7 ± 16.3 kcal/day. The fat and fat-free mass changes were estimated with an error of 0.44 ± 1.16 g/day for fat and -2.6 ± 64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake and/or daily macronutrient oxidation rate and the daily body composition change from directly measured serial data are optimally predicted with a self-adaptive model with Kalman filter that uses recursive system identification.

  9. Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high-fat diet-fed mice.

    Science.gov (United States)

    Katsumura, Masanori; Takagi, Shoko; Oya, Hana; Tamura, Shohei; Saneyasu, Takaoki; Honda, Kazuhisa; Kamisoyama, Hiroshi

    2017-08-01

    Animal by-products can be recycled and used as sources of essential nutrients. Water-soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high-fat diet. Exercise-trained mice had significantly less perirenal adipose tissue, whereas WSHI-fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone-sensitive lipase. WSHI-fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation-related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism-related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high-fat diet. © 2016 Japanese Society of Animal Science.

  10. Training with low muscle glycogen enhances fat metabolism in well-trained cyclists.

    Science.gov (United States)

    Hulston, Carl J; Venables, Michelle C; Mann, Chris H; Martin, Cara; Philp, Andrew; Baar, Keith; Jeukendrup, Asker E

    2010-11-01

    To determine the effects of training with low muscle glycogen on exercise performance, substrate metabolism, and skeletal muscle adaptation. Fourteen well-trained cyclists were pair-matched and randomly assigned to HIGH- or LOW-glycogen training groups. Subjects performed nine aerobic training (AT; 90 min at 70% VO2max) and nine high-intensity interval training sessions (HIT; 8 × 5-min efforts, 1-min recovery) during a 3-wk period. HIGH trained once daily, alternating between AT on day 1 and HIT the following day, whereas LOW trained twice every second day, first performing AT and then, 1 h later, performing HIT. Pretraining and posttraining measures were a resting muscle biopsy, metabolic measures during steady-state cycling, and a time trial. Power output during HIT was 297 ± 8 W in LOW compared with 323 ± 9 W in HIGH (P free fatty acid oxidation was similar before and after training in both groups, but muscle-derived triacylglycerol oxidation increased after training in LOW (from 16 ± 1 to 23 ± 1 μmol·kg−¹·min−¹, P glycogen also increased β-hydroxyacyl-CoA-dehydrogenase protein content (P glycogen reduced training intensity and, in performance, was no more effective than training with high muscle glycogen. However, fat oxidation was increased after training with low muscle glycogen, which may have been due to the enhanced metabolic adaptations in skeletal muscle.

  11. The Apolipoprotein M/S1P Axis Controls Triglyceride Metabolism and Brown Fat Activity

    Directory of Open Access Journals (Sweden)

    Christina Christoffersen

    2018-01-01

    Full Text Available Summary: Apolipoprotein M (apoM is the carrier of sphingosine-1-phosphate (S1P in plasma high-density lipoproteins. S1P is a bioactive lipid interacting with five receptors (S1P1–5. We show that lack of apoM in mice increases the amount of brown adipose tissue (BAT, accelerates the clearance of postprandial triglycerides, and protects against diet-induced obesity (i.e., a phenotype similar to that induced by cold exposure or β3-adrenergic stimulation. Moreover, the data suggest that the phenotype of apoM-deficient mice is S1P dependent and reflects diminished S1P1 stimulation. The results reveal a link between the apoM/S1P axis and energy metabolism. : Apolipoprotein M (apoM is the carrier of sphingosine-1-phosphate (S1P in lipoproteins. Christoffersen et al. show that lack of apoM in mice increases the amount of brown adipose tissue, accelerates the turnover of fat, and protects against obesity. The results reveal a link between the apoM/S1P axis and energy metabolism. Keywords: apolipoproteins, sphingolipids, sphingosine-1-phosphate, lipoproteins, lipid metabolism, triglyceride, brown adipose tissue, apoM

  12. Metabolism and secretory function of white adipose tissue: effect of dietary fat

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    Cláudia M. Oller do Nascimento

    2009-09-01

    Full Text Available Approximately 40% of the total energy consumed by western populations is represented by lipids, most of them being ingested as triacylglycerols and phospholipids. The focus of this review is to analyze the effect of the type of dietary fat on white adipose tissue metabolism and secretory function, particularly on haptoglobin, TNF-α, plasminogen activator inhibitor-1 and adiponectin secretion. Previous studies have demonstrated that the duration of the exposure to the high-fat feeding, amount of fatty acid present in the diet and the type of fatty acid may or may not have a significant effect on adipose tissue metabolism. However, the long-term or short-term high fat diets, especially rich in saturated fatty acids, probably by activation of toll-like receptors, stimulated the expression of proinflammatory adipokines and inhibited adiponectin expression. Further studies are needed to investigate the cellular mechanisms by which dietary fatty acids affect white adipose tissue metabolism and secretory functions.Aproximadamente 40% do total de energia consumida pela população ocidental é representada pelos lipídios, a maioria dela sendo ingerida na forma de triglicerídeos e fosfolipídios. O foco desta revisão foi analisar o efeito dos tipos de gordura da dieta sobre o metabolismo e função secretora do tecido adiposo branco, principalmente, sobre a secreção de haptoglobina, TNF-α, inibidor do ativador de plasminogênio-1 e adiponectina. Estudos prévios demonstraram que durante a exposição de dietas hiperlipídicas, a quantidade e o tipo de ácidos graxos presentes na dieta podem ou não ter um efeito significante sobre o metabolismo do tecido adiposo. Entretanto, o tratamento a curto ou longo prazo com dieta hiperlipídica, especialmente rica em ácidos graxos saturados, provavelmente por ativar receptores toll-like, estimula a expressão de adipocinas pró-inflamatórias e inibe a expressão de adiponectina. Estudos adicionais s

  13. Changes in gene expression and sensitivity of cocaine reward produced by a continuous fat diet.

    Science.gov (United States)

    Blanco-Gandía, M Carmen; Aracil-Fernández, Auxiliadora; Montagud-Romero, Sandra; Aguilar, Maria A; Manzanares, Jorge; Miñarro, José; Rodríguez-Arias, Marta

    2017-08-01

    Preclinical studies report that free access to a high-fat diet (HFD) alters the response to psychostimulants. The aim of the present study was to examine how HFD exposure during adolescence modifies cocaine effects. Gene expression of CB1 and mu-opioid receptors (MOr) in the nucleus accumbens (N Acc) and prefrontal cortex (PFC) and ghrelin receptor (GHSR) in the ventral tegmental area (VTA) were assessed. Mice were allowed continuous access to fat from PND 29, and the locomotor (10 mg/kg) and reinforcing effects of cocaine (1 and 6 mg/kg) on conditioned place preference (CPP) were evaluated on PND 69. Another group of mice was exposed to a standard diet until the day of post-conditioning, on which free access to the HFD began. HFD induced an increase of MOr gene expression in the N Acc, but decreased CB1 receptor in the N Acc and PFC. After fat withdrawal, the reduction of CB1 receptor in the N Acc was maintained. Gene expression of GHSR in the VTA decreased during the HFD and increased after withdrawal. Following fat discontinuation, mice exhibited increased anxiety, augmented locomotor response to cocaine, and developed CPP for 1 mg/kg cocaine. HFD reduced the number of sessions required to extinguish the preference and decreased sensitivity to drug priming-induced reinstatement. Our results suggest that consumption of a HFD during adolescence induces neurobiochemical changes that increased sensitivity to cocaine when fat is withdrawn, acting as an alternative reward.

  14. Influence of apolipoprotein-E gene on lipid profile, physical activity and body fat relationship

    Directory of Open Access Journals (Sweden)

    Thales Boaventura Rachid Nascimento

    2012-03-01

    Full Text Available Physical activity and body fat modify lipemia, and this effect seems to be influenced by apolipoprotein-E (APOE gene polymorphism. Thus, the purpose of this article was to review main results of studies that have analyzed the relation of APOE gene with physical activity and body fat on triglycerides, total cholesterol and low (LDL and high density lipoprotein (HDL concentrations. The Scientific Electronic Library Online – SciELO, Web of Science and PubMed database were used to locate the articles. The keywords used in combination were: apoe genotype, apolipoprotein-E polymorphism, physical exercise, physical activity, aerobic exercise, body fat and obesity. Originals scientific investigations performed with humans were included, and excluded those ones which involved samples with diseases, except obesity and/or lipemic disorders. It was observed a trend, that ε2 allele carriers are the ones with the greater improvements on lipemia from physical exercise. In addition, the body fat impact on the elevation of triglycerides and LDL are stronger in carriers of the ε2 and ε4 allele, respectively. Considering the small number of originals scientific investigations and their divergent results, reliable inferences can not be made about the APOE gene polymorphism influences on physical activity and body fat effect on lipemia. Thus, further studies with others populations and more volunteers for allele, as well as others exercise modalities and intensities, are necessary.

  15. A high-fat diet differentially affects the gut metabolism and blood lipids of rats depending on the type of dietary fat and carbohydrate.

    Science.gov (United States)

    Jurgoński, Adam; Juśkiewicz, Jerzy; Zduńczyk, Zenon

    2014-02-03

    The aim of this model study was to investigate how selected gut functions and serum lipid profile in rats on high-fat diets differed according to the type of fat (saturated vs. unsaturated) and carbohydrate (simple vs. complex). The experiment was conducted using 32 male Wistar rats distributed into 4 groups of 8 animals each. For 4 weeks, the animals were fed group-specific diets that were either rich in lard or soybean oil (16% of the diet) as the source of saturated or unsaturated fatty acids, respectively; further, each lard- and soybean oil-rich diet contained either fructose or corn starch (45.3% of the diet) as the source of simple or complex carbohydrates, respectively. Both dietary factors contributed to changes in the caecal short-chain fatty acid concentrations, especially to the butyrate concentration, which was higher in rats fed lard- and corn starch-rich diets compared to soybean oil- and fructose-rich diets, respectively. The lowest butyrate concentration was observed in rats fed the soybean oil- and fructose-rich diet. On the other hand, the lard- and fructose-rich diet vs. the other dietary combinations significantly increased serum total cholesterol concentration, to more than two times serum triglyceride concentration and to more than five times the atherogenic index. In conclusion, a high-fat diet rich in fructose can unfavorably affect gut metabolism when unsaturated fats are predominant in the diet or the blood lipids when a diet is rich in saturated fats.

  16. Pancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity.

    Science.gov (United States)

    Staaf, Johan; Labmayr, Viktor; Paulmichl, Katharina; Manell, Hannes; Cen, Jing; Ciba, Iris; Dahlbom, Marie; Roomp, Kirsten; Anderwald, Christian-Heinz; Meissnitzer, Matthias; Schneider, Reinhard; Forslund, Anders; Widhalm, Kurt; Bergquist, Jonas; Ahlström, Håkan; Bergsten, Peter; Weghuber, Daniel; Kullberg, Joel

    2017-03-01

    Adolescents with obesity have increased risk of type 2 diabetes and metabolic syndrome (MetS). Pancreatic fat has been related to these conditions; however, little is known about associations in pediatric obesity. The present study was designed to explore these associations further. We examined 116 subjects, 90 with obesity. Anthropometry, MetS, blood samples, and oral glucose tolerance tests were assessed using standard techniques. Pancreatic fat fraction (PFF) and other fat depots were quantified using magnetic resonance imaging. The PFF was elevated in subjects with obesity. No association between PFF and body mass index-standard deviation score (BMI-SDS) was found in the obesity subcohort. Pancreatic fat fraction correlated to Insulin Secretion Sensitivity Index-2 and Homeostatic Model Assessment of Insulin Resistance in simple regression; however, when using adjusted regression and correcting for BMI-SDS and other fat compartments, PFF correlated only to visceral adipose tissue and fasting glucose. Highest levels of PFF were found in subjects with obesity and MetS. In adolescents with obesity, PFF is elevated and associated to MetS, fasting glucose, and visceral adipose tissue but not to beta-cell function, glucose tolerance, or BMI-SDS. This study demonstrates that conclusions regarding PFF and its associations depend on the body mass features of the cohort.

  17. Dietary fat composition influences tissue lipid profile and gene expression in Fischer-344 rats.

    Science.gov (United States)

    Zhou, Albert L; Hintze, Korry J; Jimenez-Flores, Rafael; Ward, Robert E

    2012-12-01

    The AIN-76A diet causes fatty liver in rodents when fed for long periods of time. The aim of this study was to utilize fatty acid analysis and transcriptomics to investigate the effects of different fat sources in the AIN-76A diet on tissue lipid profiles and gene expression in male, weanling Fischer-344 rats. Animals were fed isocaloric diets that differed only in the fat source: (1) corn oil (CO) (2) anhydrous milk fat (AMF), and (3) AMF supplemented with 10% phospholipids from the milk fat globule membrane (AMF-MFGM). There were no differences in food intake, body weight, growth rate, or body fat composition among the groups, and the fatty acid compositions of red blood cells (RBC), plasma, muscle, and visceral adipose tissues reflected the dietary fat sources. Modifying the fat source resulted in 293 genes differentially regulated in skeletal muscle, 1,124 in adipose, and 831 in liver as determined by analysis of variance (ANOVA). Although tissue fatty acid profiles mostly reflected the diet, there were several quantitative differences in lipid classes in the liver and plasma. The AMF diet resulted in the highest level of hepatic triacylglycerols, but the lowest level in plasma. The CO diet resulted in significant accumulation of hepatic unesterified fatty acids and decreased DGAT expression and activity, a potential trigger for steatohepatitis. These results indicate that the fatty acid composition and presence of polar lipids in the AIN-76A diets have significant effects on lipid partitioning, gene expression, and potentially the development of liver pathology.

  18. Differentially expressed genes in the fat body of Bombyx mori in response to phoxim insecticide.

    Science.gov (United States)

    Gu, Z Y; Li, F C; Wang, B B; Xu, K Z; Ni, M; Zhang, H; Shen, W D; Li, B

    2015-01-01

    The silkworm, Bombyx mori, is an economically important insect. However, poisoning of silkworms by organophosphate pesticides causes tremendous loss to the sericulture. The fat body is the major tissue involved in detoxification and produces antimicrobial peptides and regulates hormones. In this study, a microarray system comprising 22,987 oligonucluotide 70-mer probes was employed to examine differentially expressed genes in the fat body of B. mori exposed to phoxim insecticide. The results showed that a total of 774 genes were differentially expressed upon phoxim exposure, including 500 up-regulated genes and 274 down-regulated genes. The expression levels of eight detoxification-related genes were up-regulated upon phoxim exposure, including six cytochrome P450s and two glutathione-S-transferases. It was firstly found that eight antimicrobial peptide genes were down-regulated, which might provide important references for studying the larvae of B. mori become more susceptible to microbial infections after phoxim treatment. In addition, we firstly detected the expression level of metamorphosis-related genes after phoxim exposure, which may lead to impacted reproduction. Our results may facilitate the overall understanding of the molecular mechanism of multiple pathways following exposure to phoxim insecticide in the fat body of B. mori. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. The composition of dietary fat alters the transcriptional profile of pathways associated with lipid metabolism in the liver and adipose tissue in the pig.

    Science.gov (United States)

    Kellner, T A; Gabler, N K; Patience, J F

    2017-08-01

    The objective was to investigate the of effect chemical composition of dietary fat on transcription of genes involved in lipid metabolism in adipose tissue and the liver via transcriptional profiling in growing pigs. A total of 48 Genetiporc 6.0 × Genetiporc F25 (PIC, Inc., Hendersonville, TN) barrows (initial BW of 44.1 ± 1.2 kg) were randomly allotted to 1 of 6 dietary treatments. Each experimental diet included 95% of a corn-soybean meal basal diet and 5% cornstarch (control; CNTR), animal-vegetable blend (AV), coconut oil (COCO), corn oil (COIL), fish oil (FO), or tallow (TAL). Pigs were sacrificed on d 10 (final BW of 51.2 ± 1.7 kg) to collect tissues. Expression normalization across samples was performed by calculating a delta cycle threshold (ΔCt) value using . Delta delta cycle threshold (ΔΔCt) values were expressed relative to the CNTR treatment. In adipose tissue, adding dietary fat, regardless of the source, decreased the mRNA abundance of compared with the CNTR ( = 0.014). Pigs fed a COIL-based diet tended to have greater adipose tissue expression of ( = 0.071) than pigs fed the other dietary fat sources tested. Abundance of mRNA was greater in adipose tissue of barrows a fed COIL-based diet than barrows fed CNTR or FO-based diets ( = 0.047). In the liver, adding dietary fat, regardless of source, increased the mRNA abundance of , , , , , and ( ≤ 0.020) and tended to increase the abundance of ( = 0.071) and ( = 0.086) compared with the CNTR. Pigs fed a TAL-based diet had greater hepatic transcription of than pigs fed CNTR-, COCO-, or FO-based diets ( = 0.013). Hepatic transcription of tended to be greater in pigs fed COCO than in pigs fed other dietary fat sources ( = 0.074). Dietary omega-3 fatty acid content tended to negatively correlate with mRNA abundance of ( = 0.065) in adipose tissue and ( = 0.063) in the liver. Dietary fat SFA content was negatively correlated with in the liver ( ≤ 0.039). Dietary fat MUFA content tended to be

  20. Association of metabolic gene polymorphisms with alcohol consumption in controls.

    NARCIS (Netherlands)

    Raimondi, S.C.; Benhamou, S.; Coutelle, C.; Garte, S.; Hayes, R.; Kiemeney, L.A.L.M.; Lazarus, P.; Marchand, L.L.; Morita, S.; Povey, A.; Romkes, M.; Zijno, A.; Taioli, E.

    2004-01-01

    The objectives were to study the association between metabolic genes involved in alcohol metabolism (CYP2E1 RsaI, CYP2E1 DraI, ADH1C, NQO1) and alcohol consumption in a large sample of healthy controls. Healthy subjects were selected from the International Collaborative Study on Genetic

  1. MTOR signaling and ubiquitin-proteosome gene expression in the preservation of fat free mass following high protein, calorie restricted weight loss

    Directory of Open Access Journals (Sweden)

    McIver Cassandra M

    2012-09-01

    Full Text Available Abstract Caloric restriction is one of the most efficient ways to promote weight loss and is known to activate protective metabolic pathways. Frequently reported with weight loss is the undesirable consequence of fat free (lean muscle mass loss. Weight loss diets with increased dietary protein intake are popular and may provide additional benefits through preservation of fat free mass compared to a standard protein, high carbohydrate diet. However, the precise mechanism by which a high protein diet may mitigate dietary weight loss induced reductions in fat free mass has not been fully elucidated. Maintenance of fat free mass is dependent upon nutrient stimulation of protein synthesis via the mTOR complex, although during caloric restriction a decrease (atrophy in skeletal muscle may be driven by a homeostatic shift favouring protein catabolism. This review evaluates the relationship between the macronutrient composition of calorie restricted diets and weight loss using metabolic indicators. Specifically we evaluate the effect of increased dietary protein intake and caloric restricted diets on gene expression in skeletal muscle, particularly focusing on biosynthesis, degradation and the expression of genes in the ubiquitin-proteosome (UPP and mTOR signaling pathways, including MuRF-1, MAFbx/atrogin-1, mTORC1, and S6K1.

  2. Impact of dietary fiber and fat on gut microbiota re-modeling and metabolic health

    DEFF Research Database (Denmark)

    Benítez-Páez, Alfonso; Gómez Del Pulgar, Eva M.; Kjølbæk, Louise

    2016-01-01

    a better understanding of the key components of the gut microbiota that are responsive to specific diets and of their effects on energy balance in order to use this information in practice. Scope and approach This review provides an up-to-date description of the influence of dietary fibers and fat on gut......Background Scientific evidence suggests that diet plays a role in obesity and its comorbidities, partly via its interactions with the individual's gut microbiota. Likewise, the individual's microbiota influences the efficacy of dietary interventions to reduce body weight. However, we require...... microbiota and the mechanisms presumably mediating their effects on metabolic health. We also discuss the main knowledge gaps and the need to gain greater understanding of the role of diet-microbe interactions in obesity and the associated comorbidities. Key findings and conclusions Dietary fibers are major...

  3. Extract of Kuding tea prevents high-fat diet-induced metabolic disorders in C57BL/6 mice via liver X receptor (LXR β antagonism.

    Directory of Open Access Journals (Sweden)

    Shengjie Fan

    Full Text Available To investigate the effects of ilex kudingcha C. J. Tseng (kuding tea, a traditional beverage in China, on the metabolic disorders in C57BL/6 mice induced by high-fat diets.For the preventive experiment, the female C57BL/6 mice were fed with a standard diet (Chow, high-fat diet (HF, and high-fat diet mixed with 0.05% ethanol extract of kuding tea (EK for 5 weeks. For the therapeutic experiment, the C57BL/6 mice were fed high-fat diet for 3 months, and then mice were split and EK was given with oral gavages for 2 weeks at 50 mg/day/kg. Body weight and daily food intake amounts were measured. At the end of treatment, the adipocyte images were assayed with a scanning electron microscope, and the fasting blood glucose, glucose tolerance test, serum lipid profile and lipids in the livers were analyzed. A reporter gene assay system was used to test the whether EK could act on nuclear receptor transcription factors, and the gene expression analysis was performed with a quantitative PCR assay.In the preventive treatment, EK blocked the body weight gain, reduced the size of the adipocytes, lowered serum triglyceride, cholesterol, LDL-cholesterol, fasting blood glucose levels and glucose tolerance in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, EK reduced the size of the white adipocytes, serum TG and fasting blood glucose levels in obese mice. With the reporter assay, EK inhibited LXRβ transactivity and mRNA expression of LXRβ target genes.We observed that EK has both preventive and therapeutic roles in metabolic disorders in mice induced with high-fat diets. The effects appear to be mediated through the antagonism of LXRβ transactivity. Our data indicate that kuding tea is a useful dietary therapy and a potential source for the development of novel anti-obesity and lipid lowering drugs.

  4. Effect of the types of dietary fats and non-dietary oils on bone metabolism.

    Science.gov (United States)

    El-Sayed, Eman; Ibrahim, Khadiga

    2017-03-04

    Nutrients beyond calcium and vitamin D have a role on bone health, and in treatment and prevention of osteoporosis. Quality and quantity of dietary fat may have consequences on skeletal health. Diets with highly saturated fat content produce deleterious effects on bone mineralization in growing animals. Conversely, dietary n-3-long chain polyunsaturated fatty acids play an important role in bone metabolism and may help in prevention and treatment of bone disease. Some reports suggest a correlation between the dietary ratio of n-6 and n-3 polyunsaturated fatty acids and bone formation. Specific dietary fatty acids were found to modulate prostanoid synthesis in bone tissue and improve bone formation in both animal and clinical trials. The skeletal benefits of dietary isoprenoids are extremely documented. Higher isoprenoids intake may relate to higher bone mineral density. Dietary supplements containing fish oil, individual polyunsaturated fatty acids, and isoprenoids could be used as adjuvant with bone medications in osteoportic conditions but their doses must be considered to avoid detrimental effect of over dosages.

  5. Effects of dietary fat on the saturated and monounsaturated fatty acid metabolism in growing pigs.

    Science.gov (United States)

    Raj, Stanisława; Skiba, Grzegorz; Sobol, Monika; Pastuszewska, Barbara

    2017-08-01

    The effect of dietary fats differing in fatty acid (FA) composition on the metabolism of saturated FA (SFA) and monounsaturated FA (MUFA) in growing pigs was investigated. The deposition of FA in the body and the fate of individual dietary FA were assessed after slaughter. Gilts with an initial body weight (BW) of 60 kg were used as experimental animals. Six pigs were slaughtered at 60 kg BW, while further 18 pigs received three isoenergetic and isonitrogen experimental diets containing linseed oil, rapeseed oil or beef tallow at 50 g/kg diet until they reached 105 kg (six pigs per group). The chemical composition and the content of FA in the whole body were determined and compared across groups. Regardless of dietary treatment, the whole body contained similar amounts of protein, fat and total FA. The total accumulation (percentage of net intake and de novo production) of SFA and MUFA was similar in all groups, but the processes of elongation and desaturation of SFA and MUFA depended upon the type of FA added to the diet. A high dietary content and intake of MUFA inhibits desaturation compared to SFA- and PUFA-rich diets, whereas a high SFA content and intake lowers elongation rate. The increasing net intake of total SFA and MUFA was associated with a lower total de novo production of these FA in the whole body of pigs.

  6. Dietary fat interacts with PCBs to induce changes in lipid metabolism in LDL receptor deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Hennig, B.; Reiterer, G.; Toborek, M.; Matveev, S.V.; Daugherty, A.; Smart, E. [Univ. of Kentucky, Lexington (United States); Robertson, L.W. [Univ. of Iowa, Iowa City (United States)

    2004-09-15

    From epidemiological studies, there is substantial evidence that cardiovascular diseases are linked to environmental pollution and that exposure to polycyclic and/or polyhalogenated aromatic hydrocarbons can lead to human cardiovascular toxicity. A major route of exposure to PCBs in humans is via oral ingestion of contaminated food products. Therefore, circulating environmental contaminants derived from diets, such as PCBs, are in intimate contact with the vascular endothelium. Endothelial activation and dysfunction is an important factor in the overall regulation of vascular lesion pathology. In addition to endothelial barrier dysfunction, another functional change in atherosclerosis is the activation of the endothelium that is manifested as an increase in the expression of specific cytokines and adhesion molecules. These cytokines and adhesion molecules are proposed to mediate the inflammatory aspects of the disease by regulating the vascular entry of leukocytes. Alterations in lipid profile and lipid metabolism as a result of exposure to PCBs may be important components of endothelial cell dysfunction. Little is known about the interaction of dietary fats and PCBs in the pathology of atherosclerosis. We have reported a significant disruption in endothelial barrier function when cells were exposed to linoleic acid. In the current study we aimed to demonstrate the PCB-fatty acid interaction in vivo and hypothesized that PCB toxicity can be modulated by the type of fat consumed.

  7. Effects of Reductions of Body Fat and Regional Adipose Tissue on Glucose and Lipid Metabolism Among Eldery Japanese

    OpenAIRE

    Shigeto, Kazuhiro; Koyama, Hiroshi; Takemoto, Tai-Ichiro

    1989-01-01

    To evaluate effects of improvement of obesity on glucose and lipid metabolism, changes of body weight, skinfolds and biochemical parameters in glucose and lipid metabolism were examined through a six month health education on excercise and diet. Subjects were 20 men and 36 women aged from 48 to 87, who had overweight and/or glucose intolerance. Weight, relative weight and fat mass were significantly reduced after the program in both sexes. Circumference ratios were reduced only in women. The ...

  8. Food chain transport of nanoparticles affects behaviour and fat metabolism in fish.

    Science.gov (United States)

    Cedervall, Tommy; Hansson, Lars-Anders; Lard, Mercy; Frohm, Birgitta; Linse, Sara

    2012-01-01

    Nano-sized (10(-9)-10(-7) m) particles offer many technical and biomedical advances over the bulk material. The use of nanoparticles in cosmetics, detergents, food and other commercial products is rapidly increasing despite little knowledge of their effect on organism metabolism. We show here that commercially manufactured polystyrene nanoparticles, transported through an aquatic food chain from algae, through zooplankton to fish, affect lipid metabolism and behaviour of the top consumer. At least three independent metabolic parameters differed between control and test fish: the weight loss, the triglycerides∶cholesterol ratio in blood serum, and the distribution of cholesterol between muscle and liver. Moreover, we demonstrate that nanoparticles bind to apolipoprotein A-I in fish serum in-vitro, thereby restraining them from properly utilising their fat reserves if absorbed through ingestion. In addition to the metabolic effects, we show that consumption of nanoparticle-containing zooplankton affects the feeding behaviour of the fish. The time it took the fish to consume 95% of the food presented to them was more than doubled for nanoparticle-exposed compared to control fish. Since many nano-sized products will, through the sewage system, end up in freshwater and marine habitats, our study provides a potential bioassay for testing new nano-sized material before manufacturing. In conclusion, our study shows that from knowledge of the molecular composition of the protein corona around nanoparticles it is possible to make a testable molecular hypothesis and bioassay of the potential biological risks of a defined nanoparticle at the organism and ecosystem level.

  9. MRNA expression of genes regulating lipid metabolism in ringed seals (Pusa hispida) from differently polluted areas.

    Science.gov (United States)

    Castelli, Martina Galatea; Rusten, Marte; Goksøyr, Anders; Routti, Heli

    2014-01-01

    There is a growing concern about the ability of persistent organic pollutants (POPs) to influence lipid metabolism. Although POPs are found at high concentrations in some populations of marine mammals, for example in the ringed seal (Pusa hispida) from the Baltic Sea, little is known about the effects of POPs on their lipid metabolism. An optimal regulation of lipid metabolism is crucial for ringed seals during the fasting/molting season. This is a physiologically stressful period, during which they rely on the energy stored in their fat reserves. The mRNA expression levels for seven genes involved in lipid metabolism were analyzed in liver and/or blubber tissue from molting ringed seals from the polluted Baltic Sea and a less polluted reference location, Svalbard (Norway). mRNA expression of genes encoding peroxisome proliferator-activated receptors (PPAR) α and γ and their target genes acyl-coenzyme A oxidase 1 (ACOX1) and cluster of differentiation 36 (CD36) were analyzed in liver. mRNA expression level of genes encoding PPARβ, PPARγ and their target genes encoding fatty acid binding protein 4 (FABP4) and adiponectin (ADIPOQ) were measured in inner and middle blubber layers. In addition, we evaluated the influence of molting status on hepatic mRNA expression of genes encoding PPARs and their target genes in ringed seals from Svalbard. Our results show higher mRNA expression of genes encoding hepatic PPARγ and adipose PPARβ, FABP4, and ADIPOQ in the Baltic seals compared to the Svalbard seals. A positive relationship between mRNA expressions of genes encoding hepatic PPARγ, adipose FABP4, adipose ADIPOQ and ΣPOP concentrations was observed. These findings suggest that lipid metabolism may be affected by contaminant exposure in the Baltic population. mRNA expression of genes encoding PPARβ, PPARγ, FABP4 and ADIPOQ were similar between the mid and inner adipose layer. Hepatic mRNA expression of genes encoding PPARα and PPARγ was higher in the pre

  10. The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism.

    Science.gov (United States)

    Kretowski, Adam; Adamska, Edyta; Maliszewska, Katarzyna; Wawrusiewicz-Kurylonek, Natalia; Citko, Anna; Goscik, Joanna; Bauer, Witold; Wilk, Juliusz; Golonko, Anna; Waszczeniuk, Magdalena; Lipinska, Danuta; Hryniewicka, Justyna; Niemira, Magdalena; Paczkowska, Magdalena; Ciborowski, Michal; Gorska, Maria

    2015-03-01

    Large-scale meta-analyses of genome-wide association studies have recently confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is associated with fasting glycemia and type 2 diabetes mellitus; however, the mechanism of this link was not well established. The aim of our study was to evaluate the functional/phenotypic differences related to rs340874 PROX1 variants. The study group comprised 945 subjects of Polish origin (including 634 with BMI > 25) without previously known dysglycemia. We analyzed behavioral patterns (diet, physical activity), body fat distribution and glucose/fat metabolism after standardized meals and during the oral glucose tolerance test. We found that the carriers of the rs340874 PROX1 CC genotype had higher nonesterified fatty acids levels after high-fat meal (p = 0.035) and lower glucose oxidation (p = 0.014) after high-carbohydrate meal in comparison with subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we found higher accumulation of visceral fat (p food consumption (p diabetes mellitus. The study may help to understand the mechanisms of visceral obesity and type 2 diabetes mellitus risk development.

  11. Nature of fatty acids in high fat diets differentially delineates obesity-linked metabolic syndrome components in male and female C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    El Akoum Souhad

    2011-12-01

    Full Text Available Abstract Background Adverse effects of high-fat diets (HFD on metabolic homeostasis are linked to adipose tissue dysfunction. The goal of this study was to examine the effect of the HFD nature on adipose tissue activity, metabolic disturbances and glucose homeostasis alterations in male mice compared with female mice. Methods C57BL/6J mice were fed either a chow diet or HFD including vegetal (VD or animal (AD fat. Body weight, plasmatic parameters and adipose tissue mRNA expression levels of key genes were evaluated after 20 weeks of HFD feeding. Results HFD-fed mice were significantly heavier than control at the end of the protocol. Greater abdominal visceral fat accumulation was observed in mice fed with AD compared to those fed a chow diet or VD. Correlated with weight gain, leptin levels in systemic circulation were increased in HFD-fed mice in both sexes with a significant higher level in AD group compared to VD group. Circulating adiponectin levels as well as adipose tissue mRNA expression levels were significantly decreased in HFD-fed male mice. Although its plasma levels remained unchanged in females, adiponectin mRNA levels were significantly reduced in adipose tissue of both HFD-fed groups with a more marked decrease in AD group compared to VD group. Only HFD-fed male mice were diabetic with increased fasting glycaemia. On the other hand, insulin levels were only increased in AD-fed group in both sexes associated with increased resistin levels. VD did not induce any apparent metabolic alteration in females despite the increased weight gain. Peroxisome Proliferator-Activated Receptors gamma-2 (PPARγ2 and estrogen receptor alpha (ERα mRNA expression levels in adipose tissue were decreased up to 70% in HFD-fed mice but were more markedly reduced in male mice as compared with female mice. Conclusions The nature of dietary fat determines the extent of metabolic alterations reflected in adipocytes through modifications in the pattern of

  12. Total and Full-Fat, but Not Low-Fat, Dairy Product Intakes are Inversely Associated with Metabolic Syndrome in Adults.

    Science.gov (United States)

    Drehmer, Michele; Pereira, Mark A; Schmidt, Maria Inês; Alvim, Sheila; Lotufo, Paulo A; Luft, Vivian C; Duncan, Bruce B

    2016-01-01

    Growing evidence suggests that dairy products may have beneficial cardiometabolic effects. The current guidelines, however, limit the intake of full-fat dairy products. We investigated the association of dairy consumption, types of dairy products, and dairy fat content with metabolic syndrome (MetSyn). We analyzed baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter cohort study of 15,105 adults aged 35-74 y. We excluded participants with known diabetes, cardiovascular diseases, or other chronic diseases, and those who had extreme values of energy intake, leaving 9835 for analysis. Dairy consumption was assessed by a food-frequency questionnaire. We computed servings per day for total and subgroups of dairy intake. We computed a metabolic risk score (MetScore) as the mean z score of waist circumference, systolic blood pressure, HDL cholesterol (negative z score), fasting triglycerides, and fasting glucose. We performed multivariable linear regression to test the association of servings per day of dairy products with MetScore. In analyses that adjusted for demographics, menopausal status, family history of diabetes, dietary intake, nondietary lifestyle factors, and body mass index, we observed a graded inverse association for MetScore with total dairy (-0.044 ± 0.01, P = 0.009 for each additional dairy servings per day) and full-fat dairy (-0.126 ± 0.03, P food intakes are inversely and independently associated with metabolic syndrome in middle-aged and older adults, associations that seem to be mediated by dairy saturated fatty acids. Dietary recommendations to avoid full-fat dairy intake are not supported by our findings. © 2016 American Society for Nutrition.

  13. Inulin oligofructose attenuates metabolic syndrome in high-carbohydrate, high-fat diet-fed rats.

    Science.gov (United States)

    Kumar, Senthil A; Ward, Leigh C; Brown, Lindsay

    2016-11-01

    Prebiotics alter bacterial content in the colon, and therefore could be useful for obesity management. We investigated the changes following addition of inulin oligofructose (IO) in the food of rats fed either a corn starch (C) diet or a high-carbohydrate, high-fat (H) diet as a model of diet-induced metabolic syndrome. IO did not affect food intake, but reduced body weight gain by 5·3 and 12·3 % in corn starch+inulin oligofructose (CIO) and high-carbohydrate, high-fat with inulin oligofructose (HIO) rats, respectively. IO reduced plasma concentrations of free fatty acids by 26·2 % and TAG by 75·8 % in HIO rats. IO increased faecal output by 93·2 %, faecal lipid excretion by 37·9 % and weight of caecum by 23·4 % and colon by 41·5 % in HIO rats. IO improved ileal morphology by reducing inflammation and improving the density of crypt cells in HIO rats. IO attenuated H diet-induced increases in abdominal fat pads (C 275 (sem 19), CIO 264 (sem 40), H 688 (sem 55), HIO 419 (sem 32) mg/mm tibial length), fasting blood glucose concentrations (C 4·5 (sem 0·1), CIO 4·2 (sem 0·1), H 5·2 (sem 0·1), HIO 4·3 (sem 0·1) mmol/l), systolic blood pressure (C 124 (sem 2), CIO 118 (sem 2), H 152 (sem 2), HIO 123 (sem 3) mmHg), left ventricular diastolic stiffness (C 22·9 (sem 0·6), CIO 22·9 (sem 0·5), H 27·8 (sem 0·5), HIO 22·6 (sem 1·2)) and plasma alanine transaminase (C 29·6 (sem 2·8), CIO 32·1 (sem 3·0), H 43·9 (sem 2·6), HIO 33·6 (sem 2·0) U/l). IO attenuated H-induced increases in inflammatory cell infiltration in the heart and liver, lipid droplets in the liver and plasma lipids as well as impaired glucose and insulin tolerance. These results suggest that increasing soluble fibre intake with IO improves signs of the metabolic syndrome by decreasing gastrointestinal carbohydrate and lipid uptake.

  14. Non-alcoholic fatty liver disease and subclinical atherosclerosis: A comparison of metabolically- versus genetically-driven excess fat hepatic storage.

    Science.gov (United States)

    Di Costanzo, Alessia; D'Erasmo, Laura; Polimeni, Licia; Baratta, Francesco; Coletta, Paola; Di Martino, Michele; Loffredo, Lorenzo; Perri, Ludovica; Ceci, Fabrizio; Montali, Anna; Girelli, Gabriella; De Masi, Bruna; Angeloni, Antonio; Catalano, Carlo; Maranghi, Marianna; Del Ben, Maria; Angelico, Francesco; Arca, Marcello

    2017-02-01

    Non-alcoholic fatty liver disease (NAFLD) is frequently associated with atherosclerosis. However, it is unclear whether this association is related to excess fat liver storage per se or to metabolic abnormalities that typically accompany NAFLD. To investigate this, we compared individuals with hepatic steatosis driven by metabolic disturbances to those with hepatic steatosis associated with the rs738409 GG genotype in the patatin-like phospholipase domain-containing 3 gene (PNPLA3). Carotid intima-media thickness (CIMT), as a surrogate marker of subclinical atherosclerosis, was measured in 83 blood donors with the mutant GG genotype (group G), 100 patients with features of metabolic syndrome (MetS) but the wildtype CC genotype (group M), and 74 blood donors with the wildtype CC genotype (controls). Fatty liver was evaluated by ultrasonography and hepatic fat fraction (HFF) was measured using magnetic resonance (MRS/MRI) in 157 subjects. Compared with group G and controls, group M subjects were older and had increased adiposity indices, dyslipidemia, insulin resistance and elevated transaminase levels (all p fatty liver on both ultrasonography and MRS/MRI. After adjustment for confounders (including severity of hepatic steatosis), the median CIMT in group M (0.84 [0.70-0.95] mm) was significantly greater than that in group G (0.66 [0.55-0.74] mm; p liver fat accumulation appeared to increase the burden of subclinical atherosclerosis only when it is associated with metabolic abnormalities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Effects of SH-reagents of different molecular size upon glucose metabolism in isolated rat fat cells

    International Nuclear Information System (INIS)

    Kather, H.; Simon, B.

    1975-01-01

    To study the role of membrane SH-groups in glucose transport of isolated rat fat cells we compared the effects of a small organic mercurial reagent p-CMB with those of a large p-CMB-derivative - p-CMB-Dextran, MW approximately 10,000 -. It could be shown that both compounds were of almost identical reactivity on fat cell homogenate metabolism. When applied to intact fat cells uncoupled p-CMB showed an 1) insulin-like enhancement of 14 C incorporation from (U- 14 C) glucose into CO 2 and triglyceride, 2) inhibition of the insulin-stimulatory effect on these parameters and 3) inhibition of basal glucose uptake dependent on the concentrations used. Identical concentrations of p-CMB-Dextran, however, failed to influence basal glucose uptake as well as the insulin mediated increase in glucose metabolism. (orig.) [de

  16. Seaweed supplements normalise metabolic, cardiovascular and liver responses in high-carbohydrate, high-fat fed rats.

    Science.gov (United States)

    Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C; Paul, Nicholas A; Brown, Lindsay

    2015-02-02

    Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330-340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium.

  17. Effects on lipid and glucose metabolism of diets with different types of fat and sugar in male fatty Zucker rats

    NARCIS (Netherlands)

    Waard, de H.

    1978-01-01

    The nutritional problem with regard to fat and sugar consumption in relation to lipid and glucose metabolism, and the ultimate goal of the study are generally outlined in Chapter 1. The obese Zucker rat was chosen as being likely a suitable animal model for a study like this. Chapter 2 is

  18. Seaweed Supplements Normalise Metabolic, Cardiovascular and Liver Responses in High-Carbohydrate, High-Fat Fed Rats

    Directory of Open Access Journals (Sweden)

    Senthil Arun Kumar

    2015-02-01

    Full Text Available Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO and Derbesia tenuissima (DT, in a rat model of human metabolic syndrome. Male Wistar rats (330–340 g were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium.

  19. Seaweed Supplements Normalise Metabolic, Cardiovascular and Liver Responses in High-Carbohydrate, High-Fat Fed Rats

    Science.gov (United States)

    Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C.; Paul, Nicholas A.; Brown, Lindsay

    2015-01-01

    Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330–340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium. PMID:25648511

  20. IMPACT OF GENETIC STRAIN ON BODY FAT LOSS, FOOD CONSUMPTION, METABOLISM, VENTILATION, AND MOTOR ACTIVITY IN FREE RUNNING FEMALE RATS

    Science.gov (United States)

    Physiologic data associated with different strains of common laboratory rat strains.This dataset is associated with the following publication:Gordon , C., P. Phillips , and A. Johnstone. Impact of Genetic Strain on Body Fat Loss, Food Consumption, Metabolism, Ventilation, and Motor Activity in Free Running Female Rats. PHYSIOLOGY AND BEHAVIOR. Elsevier Science Ltd, New York, NY, USA, 153: 56-63, (2016).

  1. Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.

    Directory of Open Access Journals (Sweden)

    Henriikka Salomäki

    Full Text Available AIMS: Despite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. MATERIALS AND METHODS: Female mice were on a high fat diet (HFD prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD and subjected to HFD at adulthood (10-11 weeks. Body weight and several metabolic parameters (e.g. body composition and glucose tolerance were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment. RESULTS: Prenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC was prominently affected both in the neonatal liver and adipose tissue. CONCLUSION: This study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood.

  2. Maternal high-fat diet associated with altered gene expression, DNA methylation, and obesity risk in mouse offspring

    Science.gov (United States)

    Zaidi, Rabab; Shah, Shyam; Oakley, M. Elsa; Pavlatos, Cassondra; El Idrissi, Samir; Xing, Xiaoyun; Li, Daofeng; Wang, Ting; Cheverud, James M.

    2018-01-01

    We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts. Maternal diet particularly affected genes involved in RNA processing, immune response, and mitochondria. Between one-quarter and one-third of differentially expressed genes contained a differentially methylated region associated with maternal diet. An offspring high-fat diet reduced overall variation in DNA methylation, increased body weight and organ weights, increased long bone lengths and weights, decreased insulin sensitivity, and changed the expression of 3,908 genes in the liver. Although the offspring were more affected by their own diet, their maternal diet had epigenetic effects lasting through adulthood, and in the daughters these effects were accompanied by phenotypic changes relevant to obesity and diabetes. PMID:29447215

  3. Effect of dairy calcium or supplementary calcium intake on postprandial fat metabolism, appetite, and subsequent energy intake

    DEFF Research Database (Denmark)

    Lorenzen, J.K.; Nielsen, S.; Holst, J.J.

    2007-01-01

    were tested in 18 subjects according to a randomized crossover design. The test meals contained high (HC meal: 172 mg/MJ), medium (MC meal: 84 mg/MJ), or low (LC meal: 15 mg/MJ) amounts of calcium from dairy products or a high amount of calcium given as a calcium carbonate supplement (Suppl meal: 183......-like peptide 1, ghrelin, peptide YY, insulin, or glucose were observed. Conclusions: Increased calcium intakes from dairy products attenuate postprandial lipidemia, most probably because of reduced fat absorption, whereas supplementary calcium carbonate does not exert such an effect. This may be due......Background: High calcium intake has been shown to increase fecal fat excretion. Objective: Our aim was to examine whether a high calcium intake from dairy products or from supplements affects postprandial fat metabolism and appetite through fat malabsorption. Design: Four different isocaloric meals...

  4. Ask yeast how to burn your fats: lessons learned from the metabolic adaptation to salt stress.

    Science.gov (United States)

    Pascual-Ahuir, Amparo; Manzanares-Estreder, Sara; Timón-Gómez, Alba; Proft, Markus

    2018-02-01

    Here, we review and update the recent advances in the metabolic control during the adaptive response of budding yeast to hyperosmotic and salt stress, which is one of the best understood signaling events at the molecular level. This environmental stress can be easily applied and hence has been exploited in the past to generate an impressively detailed and comprehensive model of cellular adaptation. It is clear now that this stress modulates a great number of different physiological functions of the cell, which altogether contribute to cellular survival and adaptation. Primary defense mechanisms are the massive induction of stress tolerance genes in the nucleus, the activation of cation transport at the plasma membrane, or the production and intracellular accumulation of osmolytes. At the same time and in a coordinated manner, the cell shuts down the expression of housekeeping genes, delays the progression of the cell cycle, inhibits genomic replication, and modulates translation efficiency to optimize the response and to avoid cellular damage. To this fascinating interplay of cellular functions directly regulated by the stress, we have to add yet another layer of control, which is physiologically relevant for stress tolerance. Salt stress induces an immediate metabolic readjustment, which includes the up-regulation of peroxisomal biomass and activity in a coordinated manner with the reinforcement of mitochondrial respiratory metabolism. Our recent findings are consistent with a model, where salt stress triggers a metabolic shift from fermentation to respiration fueled by the enhanced peroxisomal oxidation of fatty acids. We discuss here the regulatory details of this stress-induced metabolic shift and its possible roles in the context of the previously known adaptive functions.

  5. [Association of fat distribution with metabolic syndrome in patients with polycystic ovary syndrome].

    Science.gov (United States)

    Luo, Xiaoyan; Xu, Liangzhi

    2012-09-01

    To study the characteristics of the metabolic syndrome (MS) in patients with polycystic ovary syndrome (PCOS). Oral glucose tolerance test (OGTT) was performed in 336 patients with PCOS, and the serum levels triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and testosterone were measured. The total incidence of MS was 18.8% in these 336 patients with PCOS. The incidence of MS increased with percent body fat (%BF) and lipid accumulation product (LAP) in patients with PCOS. The patients at child-bearing age appeared to have a higher incidence of MS than those in puberty. The muscle distribution coefficient, age, body mass index, and the metabolic parameters were all higher in patients with MS than in those without MS. The bilateral lower limb muscle strength were lower in patients with MS than in those without, but the level of testosterone showed no significant difference between them. The risk of MS increases with BF%, age and LAP in patients with PCOS.

  6. Perirenal Fat and Association With Metabolic Risk Factors: The Uberlândia Heart Study.

    Science.gov (United States)

    Roever, Leonardo; Resende, Elmiro S; Veloso, Fernando C; Diniz, Angélica L D; Penha-Silva, Nilson; Casella-Filho, Antonio; Dourado, Paulo M M; Chagas, Antonio C P

    2015-09-01

    Perirenal fat (PRF) is associated with cardiovascular risk factors. Gender differences in the correlations of cardiovascular disease risk factors and PRF in the Brazilian population are lacking.Cross-sectional study with 101 (50.49% men; mean age 56.5 ± 18, range 19-74 years) drawn from the Uberlândia Heart Study underwent ultrasonography assessment of abdominal adipose. For the PRF, a 3.5 MHz transducer was measured in the middle third of the right kidney, with the transducer positioned at the axillary midline. The examinations were always performed by the same examiner. The PRF thickness was examined in relation to waist circumference, blood pressure, and metabolic risk factors. The PRF was significantly associated with the levels of gamma-glutamyl transferase (P < 0.05, r = 0.08), fasting plasma glucose (P < 0.05, r = 0.07), waist circumference (P < 0.05, r = 0.10), and metabolic syndrome (P < 0.001, r = 0.38) in men, and with the levels of fasting plasma glucose (P < 0.05) in women.The PRF was correlated with most cardiovascular risk factors in men and only in glucose at the women.

  7. Daily stressors, past depression, and metabolic responses to high-fat meals: a novel path to obesity.

    Science.gov (United States)

    Kiecolt-Glaser, Janice K; Habash, Diane L; Fagundes, Christopher P; Andridge, Rebecca; Peng, Juan; Malarkey, William B; Belury, Martha A

    2015-04-01

    Depression and stress promote obesity. This study addressed the impact of daily stressors and a history of major depressive disorder (MDD) on obesity-related metabolic responses to high-fat meals. This double-blind, randomized, crossover study included serial assessments of resting energy expenditure (REE), fat and carbohydrate oxidation, triglycerides, cortisol, insulin, and glucose before and after two high-fat meals. During two separate 9.5-hour admissions, 58 healthy women (38 breast cancer survivors and 20 demographically similar control subjects), mean age 53.1 years, received either a high saturated fat meal or a high oleic sunflower oil meal. Prior day stressors were assessed by the Daily Inventory of Stressful Events. Greater numbers of stressors were associated with lower postmeal REE (p = .008), lower fat oxidation (p = .04), and higher insulin (p = .01), with nonsignificant effects for cortisol and glucose. Women with prior MDD had higher cortisol (p = .008) and higher fat oxidation (p = .004), without significant effects for REE, insulin, and glucose. Women with a depression history who also had more stressors had a higher peak triglyceride response than other participants (p = .01). The only difference between meals was higher postprandial glucose following sunflower oil compared with saturated fat (p = .03). The cumulative 6-hour difference between one prior day stressor and no stressors translates into 435 kJ, a difference that could add almost 11 pounds per year. These findings illustrate how stress and depression alter metabolic responses to high-fat meals in ways that promote obesity. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. High intake of regular-fat cheese compared with reduced-fat cheese does not affect LDL cholesterol or risk markers of the metabolic syndrome

    DEFF Research Database (Denmark)

    Raziani, Farinaz; Tholstrup, Tine; Kristensen, Marlene Dahlwad

    2016-01-01

    was to compare the effects of regular-fat cheese with an equal amount of reduced-fat cheese and an isocaloric amount of carbohydrate-rich foods on LDL cholesterol and risk factors for the metabolic syndrome (MetS). DESIGN: The study was a 12-wk randomized parallel intervention preceded by a 2-wk run-in period...... MJ, whereas subjects in the CHO group did the same with bread and jam corresponding to 90 g and 25 g/10 MJ, respectively. RESULTS: A total of 139 subjects completed the intervention. The primary outcome, LDL cholesterol, was not significantly different between the REG and RED diets or between the REG...... circumference did not differ significantly between the 3 diets. CONCLUSION: A high daily intake of regular-fat cheese for 12 wk did not alter LDL cholesterol or MetS risk factors differently than an equal intake of reduced-fat cheese or an isocaloric amount of carbohydrate-rich foods. This trial was registered...

  9. Characterization of fat metabolism in the fatty liver caused by a high-fat, low-carbohydrate diet: A study under equal energy conditions.

    Science.gov (United States)

    Kurosaka, Yuka; Shiroya, Yoko; Yamauchi, Hideki; Kitamura, Hiromi; Minato, Kumiko

    2017-05-20

    The pathology of fatty liver due to increased percentage of calories derived from fat without increased overall caloric intake is largely unclear. In this study, we aimed to characterize fat metabolism in rats with fatty liver resulting from consumption of a high-fat, low-carbohydrate (HFLC) diet without increased caloric intake. Four-week-old male Sprague-Dawley rats were randomly assigned to the control (Con) and HFLC groups, and rats were fed the corresponding diets ad libitum. Significant decreases in food intake per gram body weight were observed in the HFLC group compared with that in the Con group. Thus, there were no significant differences in body weights or caloric intake per gram body weight between the two groups. Marked progressive fat accumulation was observed in the livers of rats in the HFLC group, accompanied by suppression of de novo lipogenesis (DNL)-related proteins in the liver and increased leptin concentrations in the blood. In addition, electron microscopic observations revealed that many lipid droplets had accumulated within the hepatocytes, and mitochondrial numbers were reduced in the hepatocytes of rats in the HFLC group. Our findings confirmed that consumption of the HFLC diet induced fatty liver, even without increased caloric intake. Furthermore, DNL was not likely to be a crucial factor inducing fatty liver with standard energy intake. Instead, ultrastructural abnormalities found in mitochondria, which may cause a decline in β-oxidation, could contribute to the development of fatty liver. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Protective effects of L-arabinose in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats

    OpenAIRE

    Lei Hao; Xiaoling Lu; Min Sun; Kai Li; Lingmin Shen; Tao Wu

    2015-01-01

    Background: L-Arabinose is a non-caloric sugar, which could affect glucose and lipid metabolism and suppress obesity. However, few reports have described the effect of L-arabinose in metabolic syndrome, a combination of medical disorders that increase the risk of diabetes and cardiovascular disease. Objective: This study was conducted to explore the effects of L-arabinose in rats with metabolic syndrome induced by a high-carbohydrate, high-fat (HCHF) diet. Methods: After the rat model for met...

  11. Comparative nontargeted profiling of metabolic changes in tissues and biofluids in high-fat diet-fed Ossabaw pig

    DEFF Research Database (Denmark)

    Hanhineva, Kati; Barri, Thaer; Kolehmainen, Marjukka

    2013-01-01

    to reveal metabolite groups for generating new hypotheses of obesity-related metabolic disturbances produced in an animal model. A large spectrum of metabolites in the semi-polar region, including small water soluble molecules like betaine and dihydroxyindole, and a wide range of bile acids as well...... as various lipid species were detected. The high fat diet influenced metabolic homeostasis of Ossabaw pigs, especially the lipid metabolome, throughout all the analyzed sample types, including plasma, urine, bile, liver, pancreas, brain cortex, intestinal jejunum and proximal colon. However, even dramatic...... and lipids, thus pointing to the pathways of metabolism affected by the dietary treatment....

  12. The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat

    DEFF Research Database (Denmark)

    Schilperoort, Maaike; van Dam, Andrea D; Hoeke, Geerte

    2018-01-01

    Brown adipose tissue (BAT) activation stimulates energy expenditure in human adults, which makes it an attractive target to combat obesity and related disorders. Recent studies demonstrated a role for G protein-coupled receptor 120 (GPR120) in BAT thermogenesis. Here, we investigated the therapeu......Brown adipose tissue (BAT) activation stimulates energy expenditure in human adults, which makes it an attractive target to combat obesity and related disorders. Recent studies demonstrated a role for G protein-coupled receptor 120 (GPR120) in BAT thermogenesis. Here, we investigated...... the therapeutic potential of GPR120 agonism and addressed GPR120-mediated signaling in BAT We found that activation of GPR120 by the selective agonist TUG-891 acutely increases fat oxidation and reduces body weight and fat mass in C57Bl/6J mice. These effects coincided with decreased brown adipocyte lipid content...... and increased nutrient uptake by BAT, confirming increased BAT activity. Consistent with these observations, GPR120 deficiency reduced expression of genes involved in nutrient handling in BAT Stimulation of brown adipocytes in vitro with TUG-891 acutely induced O2 consumption, through GPR120-dependent and GPR...

  13. Specificity Protein 1 Regulates Gene Expression Related to Fatty Acid Metabolism in Goat Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Jiangjiang Zhu

    2015-01-01

    Full Text Available Specificity protein 1 (SP1 is a ubiquitous transcription factor that plays an important role in controlling gene expression. Although important in mediating the function of various hormones, the role of SP1 in regulating milk fat formation remains unknown. To investigate the sequence and expression information, as well as its role in modulating lipid metabolism, we cloned SP1 gene from mammary gland of Xinong Saanen dairy goat. The full-length cDNA of the SP1 gene is 4376 bp including 103 bp of 5'UTR, 2358 bp of ORF (HM_236311 and 1915 bp of 3'UTR, which is predicted to encode a 786 amino acids polypeptide. Phylogenetic tree analysis showed that goat SP1 has the closest relationship with sheep, followed by bovines (bos taurus, odobenus and ceratotherium, pig, primates (pongo, gorilla, macaca and papio and murine (rattus and mus, while the furthest relationship was with canis and otolemur. Expression was predominant in the lungs, small intestine, muscle, spleen, mammary gland and subcutaneous fat. There were no significant expression level differences between the mammary gland tissues collected at lactation and dry-off period. Overexpression of SP1 in goat mammary epithelial cells (GMECs led to higher mRNA expression level of peroxisome proliferator-activated receptor-γ (PPARγ and lower liver X receptor α (LXRα mRNA level, both of which were crucial in regulating fatty acid metabolism, and correspondingly altered the expression of their downstream genes in GMECs. These results were further enhanced by the silencing of SP1. These findings suggest that SP1 may play an important role in fatty acid metabolism.

  14. Consumption of Yogurt, Low-Fat Milk, and Other Low-Fat Dairy Products Is Associated with Lower Risk of Metabolic Syndrome Incidence in an Elderly Mediterranean Population.

    Science.gov (United States)

    Babio, Nancy; Becerra-Tomás, Nerea; Martínez-González, Miguel Ángel; Corella, Dolores; Estruch, Ramon; Ros, Emilio; Sayón-Orea, Carmen; Fitó, Montserrat; Serra-Majem, Lluís; Arós, Fernando; Lamuela-Raventós, Rosa M; Lapetra, José; Gómez-Gracia, Enrique; Fiol, Miguel; Díaz-López, Andrés; Sorlí, José V; Martínez, J Alfredo; Salas-Salvadó, Jordi

    2015-10-01

    The association between consumption of dairy products and the risk of developing metabolic syndrome (MetS) is unclear. The purpose of this study was to evaluate the associations between consumption of dairy products (total and different subtypes) and incident MetS in a Mediterranean population at high cardiovascular disease risk. We prospectively analyzed 1868 men and women (55-80 y old) without MetS at baseline, recruited from different PREDIMED (Prevención con Dieta Mediterránea) centers between October 2003 and June 2009 and followed up until December 2010. MetS was defined according to updated, harmonized criteria. At baseline and yearly thereafter, we determined anthropometric variables, dietary habits by a 137-item validated food-frequency questionnaire, and blood biochemistry. Multivariable-adjusted HRs of MetS or its components were estimated for each of the 2 upper tertiles (vs. the lowest one) of mean consumption of dairy products during the follow-up. During a median follow-up of 3.2 y, we documented 930 incident MetS cases. In the multivariable-adjusted model, HRs (95% CIs) of MetS for the comparison of extreme tertiles of dairy product consumption were 0.72 (0.61, 0.86) for low-fat dairy, 0.73 (0.62, 0.86) for low-fat yogurt, 0.78 (0.66, 0.92) for whole-fat yogurt, and 0.80 (0.67, 0.95) for low-fat milk. The respective HR for cheese was 1.31 (1.10, 1.56). Higher consumption of low-fat dairy products, yogurt (total, low-fat, and whole-fat yogurt) and low-fat milk was associated with a reduced risk of MetS in individuals at high cardiovascular disease risk from a Mediterranean population. Conversely, higher consumption of cheese was related to a higher risk of MetS. This trial was registered at controlled-trials.com as ISRCTN35739639. © 2015 American Society for Nutrition.

  15. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

    DEFF Research Database (Denmark)

    de Castro Barbosa, Thais; Ingerslev, Lars R; Alm, Petter S

    2016-01-01

    OBJECTIVES: Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. METHODS: F0-male rats fed either HFD or chow diet...... for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing. RESULTS: Newborn offspring of HFD-fed fathers had reduced body weight......1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. CONCLUSION: Our results provide insight...

  16. Effects of Metabolic Programming on Juvenile Play Behavior and Gene Expression in the Prefrontal Cortex of Rats.

    Science.gov (United States)

    Hehar, Harleen; Ma, Irene; Mychasiuk, Richelle

    2016-01-01

    Early developmental processes, such as metabolic programming, can provide cues to an organism, which allow it to make modifications that are predicted to be beneficial for survival. Similarly, social play has a multifaceted role in promoting survival and fitness of animals. Play is a complex behavior that is greatly influenced by motivational and reward circuits, as well as the energy reserves and metabolism of an organism. This study examined the association between metabolic programming and juvenile play behavior in an effort to further elucidate insight into the consequences that early adaptions have on developmental trajectories. The study also examined changes in expression of four genes (Drd2, IGF1, Opa1, and OxyR) in the prefrontal cortex known to play significant roles in reward, bioenergetics, and social-emotional functioning. Using four distinct variations in developmental programming (high-fat diet, caloric restriction, exercise, or high-fat diet combined with exercise), we found that dietary programming (high-fat diet vs. caloric restriction) had the greatest impact on play behavior and gene expression. However, exercise also induced changes in both measures. This study demonstrates that metabolic programming can alter neural circuits and bioenergetics involved in play behavior, thus providing new insights into mechanisms that allow programming to influence the evolutionary success of an organism. © 2016 S. Karger AG, Basel.

  17. The genetics of fat distribution.

    Science.gov (United States)

    Schleinitz, Dorit; Böttcher, Yvonne; Blüher, Matthias; Kovacs, Peter

    2014-07-01

    Fat stored in visceral depots makes obese individuals more prone to complications than subcutaneous fat. There is good evidence that body fat distribution (FD) is controlled by genetic factors. WHR, a surrogate measure of FD, shows significant heritability of up to ∼60%, even after adjusting for BMI. Genetic variants have been linked to various forms of altered FD such as lipodystrophies; however, the polygenic background of visceral obesity has only been sparsely investigated in the past. Recent genome-wide association studies (GWAS) for measures of FD revealed numerous loci harbouring genes potentially regulating FD. In addition, genes with fat depot-specific expression patterns (in particular subcutaneous vs visceral adipose tissue) provide plausible candidate genes involved in the regulation of FD. Many of these genes are differentially expressed in various fat compartments and correlate with obesity-related traits, thus further supporting their role as potential mediators of metabolic alterations associated with a distinct FD. Finally, developmental genes may at a very early stage determine specific FD in later life. Indeed, genes such as TBX15 not only manifest differential expression in various fat depots, but also correlate with obesity and related traits. Moreover, recent GWAS identified several polymorphisms in developmental genes (including TBX15, HOXC13, RSPO3 and CPEB4) strongly associated with FD. More accurate methods, including cardiometabolic imaging, for assessment of FD are needed to promote our understanding in this field, where the main focus is now to unravel the yet unknown biological function of these novel 'fat distribution genes'.

  18. Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors in mice.

    Science.gov (United States)

    Laugerette, Fabienne; Furet, Jean-Pierre; Debard, Cyrille; Daira, Patricia; Loizon, Emmanuelle; Géloën, Alain; Soulage, Christophe O; Simonet, Claire; Lefils-Lacourtablaise, Jennifer; Bernoud-Hubac, Nathalie; Bodennec, Jacques; Peretti, Noël; Vidal, Hubert; Michalski, Marie-Caroline

    2012-02-01

    Low-grade inflammation observed in obesity is a risk factor for cardiovascular disease. Recent studies revealed that this would be linked to gut-derived endotoxemia during fat digestion in high-fat diets, but nothing is known about the effect of lipid composition. The study was designed to test the impact of oil composition of high-fat diets on endotoxin metabolism and inflammation in mice. C57/Bl6 mice were fed for 8 wk with chow or isocaloric isolipidic diets enriched with oils differing in fatty acid composition: milk fat, palm oil, rapeseed oil, or sunflower oil. In vitro, adipocytes (3T3-L1) were stimulated or not with lipopolysaccharide (LPS; endotoxin) and incubated with different fatty acids. In mice, the palm group presented the highest level of IL-6 in plasma (P palm group was correlated with a greater ratio of LPS-binding protein (LBP)/sCD14 in plasma (P palm group, which was associated with lower inflammation in both plasma and adipose tissue despite higher plasma endotoxemia. Taken together, our results reveal that the palm oil-based diet resulted in the most active transport of LPS toward tissues via high LBP and low sCD14 and the greatest inflammatory outcomes. In contrast, a rapeseed oil-based diet seemed to result in an endotoxin metabolism driven toward less inflammatory pathways. This shows that dietary fat composition can contribute to modulate the onset of low-grade inflammation through the quality of endotoxin receptors.

  19. A High-Fat Diet Differentially Affects the Gut Metabolism and Blood Lipids of Rats Depending on the Type of Dietary Fat and Carbohydrate

    Directory of Open Access Journals (Sweden)

    Adam Jurgoński

    2014-02-01

    Full Text Available The aim of this model study was to investigate how selected gut functions and serum lipid profile in rats on high-fat diets differed according to the type of fat (saturated vs. unsaturated and carbohydrate (simple vs. complex. The experiment was conducted using 32 male Wistar rats distributed into 4 groups of 8 animals each. For 4 weeks, the animals were fed group-specific diets that were either rich in lard or soybean oil (16% of the diet as the source of saturated or unsaturated fatty acids, respectively; further, each lard- and soybean oil-rich diet contained either fructose or corn starch (45.3% of the diet as the source of simple or complex carbohydrates, respectively. Both dietary factors contributed to changes in the caecal short-chain fatty acid concentrations, especially to the butyrate concentration, which was higher in rats fed lard- and corn starch-rich diets compared to soybean oil- and fructose-rich diets, respectively. The lowest butyrate concentration was observed in rats fed the soybean oil- and fructose-rich diet. On the other hand, the lard- and fructose-rich diet vs. the other dietary combinations significantly increased serum total cholesterol concentration, to more than two times serum triglyceride concentration and to more than five times the atherogenic index. In conclusion, a high-fat diet rich in fructose can unfavorably affect gut metabolism when unsaturated fats are predominant in the diet or the blood lipids when a diet is rich in saturated fats.

  20. Metabolic syndrome alters expression of insulin signaling-related genes in swine mesenchymal stem cells.

    Science.gov (United States)

    Conley, Sabena M; Zhu, Xiang-Yang; Eirin, Alfonso; Tang, Hui; Lerman, Amir; van Wijnen, Andre J; Lerman, Lilach O

    2018-02-20

    Metabolic syndrome (MetS) is associated with insulin resistance (IR) and impaired glucose metabolism in muscle, fat, and other cells, and may induce inflammation and vascular remodeling. Endogenous reparative systems, including adipose tissue-derived mesenchymal stem/stromal cells (MSC), are responsible for repair of damaged tissue. MSC have also been proposed as an exogenous therapeutic intervention in patients with cardiovascular and chronic kidney disease (CKD). The feasibility of using autologous cells depends on their integrity, but whether in MetS IR involves adipose tissue-derived MSC remains unknown. The aim of this study was to examine the expression of mRNA involved in insulin signaling in MSC from subjects with MetS. Domestic pigs consumed a lean or obese diet (n=6 each) for 16weeks. MSC were collected from subcutaneous abdominal fat and analyzed using high-throughput RNA-sequencing for expression of genes involved in insulin signaling. Expression profiles for enriched (fold change>1.4, pinsulin signaling. Enriched mRNAs were implicated in biological pathways including hepatic glucose metabolism, adipocyte differentiation, and transcription regulation, and down-regulated mRNAs in intracellular calcium signaling and cleaving peptides. Functional analysis suggested that overall these alterations could increase IR. MetS alters mRNA expression related to insulin signaling in adipose tissue-derived MSC. These observations mandate caution during administration of autologous MSC in subjects with MetS. Copyright © 2017. Published by Elsevier B.V.

  1. Differences in muscle and adipose tissue gene expression and cardio-metabolic risk factors in the members of physical activity discordant twin pairs.

    Science.gov (United States)

    Leskinen, Tuija; Rinnankoski-Tuikka, Rita; Rintala, Mirva; Seppänen-Laakso, Tuulikki; Pöllänen, Eija; Alen, Markku; Sipilä, Sarianna; Kaprio, Jaakko; Kovanen, Vuokko; Rahkila, Paavo; Oresic, Matej; Kainulainen, Heikki; Kujala, Urho M

    2010-09-16

    High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50-74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased 'high-risk' ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are associated with reduced

  2. Differences in muscle and adipose tissue gene expression and cardio-metabolic risk factors in the members of physical activity discordant twin pairs.

    Directory of Open Access Journals (Sweden)

    Tuija Leskinen

    Full Text Available High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50-74 years who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased 'high-risk' ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are

  3. Visceral Fat Area and Serum Adiponectin Level Predict the Development of Metabolic Syndrome in a Community-Based Asymptomatic Population.

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    Sang-A Cho

    Full Text Available Although it has been demonstrated that visceral adipose tissue content and serum levels of adiponectin are associated with metabolic syndrome, their predictive potential for the development of metabolic syndrome remains to be elucidated.We studied 1,130 participants of the Seoul Metabolic Syndrome cohort. A total of 337 subjects without metabolic syndrome underwent the follow-up evaluation and finally analyzed. Visceral fat area (VFA was measured using dual bioelectrical impedance analysis. We compared the 1-year incidence rate of metabolic syndrome among four different groups: Group 1 (high adiponectin level and low VFA, Group 2 (low adiponectin level and low VFA, Group 3 (high adiponectin level and high VFA and Group 4 (low adiponectin level and high VFA.Median follow-up duration was 17 months. Cut-off points of adiponectin level and VFA for metabolic syndrome were 7.34 ng/ml and 84 cm2 for men, and 12.55 and 58 cm2 ng/ml for women, respectively. The incidence of metabolic syndrome was the highest in Group 4 (Group 1; 16.47%, Group 2; 22.08%, Group 3; 25%, and Group 4; 46.15%, p<0.001. Adjusted logistic regression analyses for metabolic syndrome prediction demonstrated that Group 4 exhibited the highest odds ratio compared with Group 1 (4.918 [2.05-11.795], which was predominantly affected by waist circumference and serum triglyceride levels. Notably, triglyceride/high-density lipoprotein cholesterol (TG/HDL ratio was significantly higher in Group 4 (p = 0.017.Incidence rate of metabolic syndrome was the highest in subjects with low serum adiponectin levels and high visceral fat area. Higher TG/HDL ratio in these subjects suggested insulin resistance may contribute to the development of metabolic syndrome.

  4. Metabolic Pathway Genes Associated with Susceptibility Genes to Coronary Artery Disease

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    Heng Lu

    2018-01-01

    Full Text Available Coronary artery disease (CAD is one of the leading threats to global health. Previous research has proven that metabolic pathway disorders, such as high blood lipids and diabetes, are one of the risk factors that mostly cause CAD. However, the crosstalk between metabolic pathways and CAD was mostly studied on physiology processes by analyzing a single gene function. A canonical correlation analysis was used to identify the metabolic pathways, which were integrated as a unit to coexpress with CAD susceptibility genes, and to resolve additional metabolic factors that are related to CAD. Seven pathways, including citrate cycle, ubiquinone, terpenoid quinone biosynthesis, and N-glycan biosynthesis, were identified as an integrated unit coexpressed with CAD genes. These pathways could not be revealed as a coexpressed pathway through traditional methods as each single gene has weak correlation. Furthermore, sets of genes in these pathways were candidate markers for diagnosis and detection from patients’ serum.

  5. Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming.

    Science.gov (United States)

    Xu, Dan; Xia, Li-ping; Shen, Lang; Lei, You-ying; Liu, Lian; Zhang, Li; Magdalou, Jacques; Wang, Hui

    2013-12-01

    Prenatal nicotine exposure (PNE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Maternal Wistar rats were injected with nicotine (1.0 mg/kg, sc) twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress (UCS) during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical "catch-up" growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration (caused further increases in the serum ACTH and corticosterone levels), but also significantly changed the glucose and lipid metabolism after UCS (caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids). The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.

  6. Metabolic regulation and the anti-obesity perspectives of human brown fat

    DEFF Research Database (Denmark)

    Scheele, Camilla; Nielsen, Søren

    2017-01-01

    is depot specific and originating from BAT. In conclusion, to utilize the anti-obesity potential of human BAT focus should be directed towards identifying novel regulators of brown and beige fat progenitor cells, as well as feedback mechanisms of BAT activation. This would allow for identification of novel...... shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat. Batokines also seems to be involved in BAT recruitment by stimulating proliferation...... and differentiation of brown fat progenitors. Increasing human BAT capacity could thus include inducing brown fat biogenesis as well as identifying novel batokines. Another attractive approach would be to induce a brown fat phenotype, the so-called brite or beige fat, within the white fat depots. In adult humans...

  7. Network analysis of hepatic genes responded to high-fat diet in C57BL/6J mice: nutrigenomics data mining from recent research findings.

    Science.gov (United States)

    Kim, Eun Jung; Kim, Eunjung; Kwon, Eun-Young; Jang, Hyun-Seo; Hur, Cheol-Goo; Choi, Myung-Sook

    2010-08-01

    Obesity and its associated complications, including diabetes, dyslipidemia, atherosclerosis, and some cancers, have been a global health problem with a rapid increase of the obese population. In this study, we selected 31 obesity candidate genes in the liver of high-fat-induced obese C57BL/6J mice through investigation of literature search and analyzed functional protein-protein interaction of the genes using the STRING database. Most of the obesity candidate genes were closely connected through lipid metabolism, and in particular acyl-coenzyme A oxidase 1 appeared to be a core obesity gene. Overall, genes involved in fatty acid beta-oxidation, fatty acid synthesis, and gluconeogenesis were up-regulated, and genes involved in sterol biosynthesis, insulin signaling, and oxidative stress defense system were down-regulated with a high-fat diet. Future identification of core obesity genes and their functional targets is expected to provide a new way to prevent obesity by phytochemicals or functional foods on the basis of food and nutritional genomics.

  8. A water-soluble extract from Cucurbita moschata shows anti-obesity effects by controlling lipid metabolism in a high fat diet-induced obesity mouse model.

    Science.gov (United States)

    Choi, Hyounjeong; Eo, Haekwan; Park, Kyoungcheol; Jin, Mirim; Park, Eun-Jin; Kim, Seon-Hee; Park, Jeong Euy; Kim, Sunyoung

    2007-08-03

    During the screening of a variety of plant sources for their anti-obesity activity, it was found that a water-soluble extract, named PG105, prepared from stem parts of Cucurbita moschata, contains potent anti-obesity activities in a high fat diet-induced obesity mouse model. In this animal model, increases in body weight and fat storage were suppressed by 8-week oral administration of PG105 at 500 mg/kg, while the overall amount of food intake was not affected. Furthermore, PG105 protected the development of fatty liver and increased the hepatic beta-oxidation activity. Results from blood analysis showed that the levels of triglyceride and cholesterol were significantly lowered by PG105 administration, and also that the level of leptin was reduced, while that of adiponectin was increased. To understand the underlying mechanism at the molecular level, the effects of PG105 were examined on the expression of the genes involved in lipid metabolism by Northern blot analysis. In the liver of PG105-treated mice, the mRNA level of lipogenic genes such as SREBP-1c and SCD-1 was decreased, while that of lipolytic genes such as PPARalpha, ACO-1, CPT-1, and UCP-2 was modestly increased. Our data suggest that PG105 may have great potential as a novel anti-obesity agent in that both inhibition of lipid synthesis and acceleration of fatty acid breakdown are induced by this reagent.

  9. A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

    Directory of Open Access Journals (Sweden)

    Erica L. Underwood

    2016-01-01

    Full Text Available While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms.

  10. Dietary nitrite reverses features of postmenopausal metabolic syndrome induced by high-fat diet and ovariectomy in mice.

    Science.gov (United States)

    Ohtake, Kazuo; Ehara, Nobuyuki; Chiba, Hiroshige; Nakano, Genya; Sonoda, Kunihiro; Ito, Junta; Uchida, Hiroyuki; Kobayashi, Jun

    2017-04-01

    Menopausal women are at greater risk of developing metabolic syndrome with reduced endothelial nitric oxide synthase (eNOS) activity. Hormone replacement therapy increases eNOS activity and normalizes some characteristics of metabolic syndrome. We hypothesized that nitric oxide (NO) supplementation should have a therapeutic effect on this syndrome. We examined the effect of dietary nitrite in a mouse model with postmenopausal metabolic syndrome induced by ovariectomy (OVX) and a high fat diet (HF). C57BL/6 female mice were divided into five groups, sham+normal fat diet (NF), sham+ HF, OVX+HF with or without sodium nitrite (50 mg and 150 mg/l) in the drinking water. Daily food intake and weekly body weight were monitored for 18 wk. OVX and HF significantly reduced plasma levels of nitrate/nitrite (NOx), and mice developed obesity with visceral hypertrophic adipocytes and increased transcriptional levels of monocyte chemoattractant protein-1, TNF-α, and IL-6 in visceral fat tissues. The proinflammatory state in the adipocytes provoked severe hepatosteatosis and insulin resistance in OVX+HF group compared with sham+NF group. However, dietary nitrite significantly suppressed adipocyte hypertrophy and transcriptions of proinflammatory cytokines in visceral fat in a dose-dependent manner. The improvement of visceral inflammatory state consequently reversed the hepatosteatosis and insulin resistance observed in OVX+HF mice. These results suggest that an endogenous NO defect might underlie postmenopausal metabolic syndrome and that dietary nitrite provides an alternative source of NO, subsequently compensating for metabolic impairments of this syndrome. Copyright © 2017 the American Physiological Society.

  11. Investigation of relationship of visceral body fat and inflammatory markers with metabolic syndrome and its components among apparently healthy individuals.

    Science.gov (United States)

    Turker, Yasemin; Baltaci, Davut; Turker, Yasin; Ozturk, Serkan; Sonmez, Cemil Isik; Deler, Mehmet Harun; Sariguzel, Yunus Cem; Sariguzel, Feyza; Ankarali, Handan

    2015-01-01

    Metabolic syndrome is a cluster of disorders and great risk for cardiovascular diseases. We aimed to investigate association between severity of metabolic syndrome (MetS) and anthropometric measurements, and to evaluate correlation of MetS and its components with metabolic deterioration and inflammatory indexes. The cross-sectional study enrolled 1474 patients with obesity and overweight. The patients were grouped as MetS and Non-MetS, and were sub-grouped as group 1 (three criteria), 2 (four criteria) and 3 (≥ five criteria) according to NCEP ATP III. Mean age was 38.7 ± 11.9 years and BMI was 35.1 ± 6.3 kg/m(2). Lipid profile, anthropometric and blood pressure measurements, liver function tests, bioelectric impedance body fat compositions, insulin resistance and HbA1c, and spot urinary albumin-creatinine ratio were significantly different between groups of MetS and Non-MetS. Age, lipid profile, bioelectric impedance fat analyses, BMI, blood pressure values, glucose, insulin resistance, uric acid and hs-CRP levels were significantly different between groups of MetS component groups. ROC analysis revealed that hs-CRP was found to be more predictive for severity of metabolic syndrome components 3 and 4 (P=0.030); uric acid and visceral fat were more actual to predict severity of metabolic syndrome between 3 and 5 MetS components, (P=0.006) and uric acid was detected as more actual to predict severity of MetS between 4 and 5 components (P=0.023). In conclusion, uric acid, hs-CRP and visceral body fat composition were useful to predict to severity of MetS in primary care.

  12. Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21

    Directory of Open Access Journals (Sweden)

    Kemin Yan

    2018-03-01

    Full Text Available Objective: Ileal transposition (IT surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21 is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with the FGF21 signaling pathway in diabetic Goto-Kakizaki (GK rats.Methods: Ten-week-old male GK rats were subjected to IT surgery with translocation of a 10 cm ileal segment to the proximal jejunum (IT group or sham surgery without the ileum transposition (Sham-IT group. Rats in the no surgery group did not receive any surgical intervention. Six weeks later, body weight, fat mass, fasting blood glucose (FBG, and serum levels of FGF21 and leptin were measured. The expression of the FGF21 signaling pathway and white adipose tissue (WAT browning-related genes in the WAT and liver were evaluated by real-time reverse transcription polymerase chain reaction (RT-qPCR and western blot.Results: IT surgery significantly decreased the body weights and FBG levels and increased the insulin sensitivity of GK rats. The total WAT mass of the IT rats showed a 41.5% reduction compared with the Sham-IT rats, and serum levels of FGF21 and leptin of the IT rats decreased by 26.3 and 61.7%, respectively (all P < 0.05. The mRNA levels of fibroblast growth factor receptor 1 (FGFR1 and its co-receptor β klotho (KLB in the perirenal WAT (pWAT of the IT rats were 1.4- and 2.4-fold that of the Sham-IT rats, respectively, and the FGFR1 protein levels were 1.7-fold of the Sham-IT rats (all P < 0.05. In accordance with the pWAT, the protein levels of FGFR1 and KLB in the epididymal WAT (eWAT of the IT rats notably increased to 3.0- and 3.9-fold of the Sham-IT rats (P < 0.05. Furthermore, uncoupling protein 1 (UCP1 protein levels in the eWAT and pWAT of the IT rats also increased to 2.2- and 2.3-fold of the Sham-IT rats (P < 0.05. However, the protein levels of FGFR1 and KLB in the

  13. Milk fat globule is an alternative to mammary epithelial cells for gene expression analysis in buffalo.

    Science.gov (United States)

    Chen, Qiuming; Wu, Yanjun; Zhang, Mingyuan; Xu, Wenwen; Guo, Xiaoping; Yan, Xueyu; Deng, Haiying; Jiang, Qinyang; Yang, Xiurong; Lan, Ganqiu; Guo, Yafen; Qin, Guangsheng; Jiang, Hesheng

    2016-05-01

    Owing to the difficulty in obtaining mammary gland tissue from lactating animals, it is difficult to test the expression levels of genes in mammary gland. The aim of the current study was to identify if milk fat globule (MFG) in buffalo milk was an alternative to mammary gland (MG) and milk somatic cell (MSC) for gene expression analysis. Six buffalos in late lactation were selected to collect MFG and MSC, and then MG was obtained by surgery. MFG was stained with acridine orange to successfully visualise RNA and several cytoplasmic crescents in MFG. The total RNA in MFG was successfully isolated and the integrity was assessed by agarose gel electrophoresis. We analysed the cellular components in MFG, MG and MSC through testing the expression of cell-specific genes by qRT-PCR. The results showed that adipocyte-specific gene (AdipoQ) and leucocyte-specific genes (CD43, CSF1 and IL1α) in MFG were not detected, whereas epithelial cell marker genes (Keratin 8 and Keratin 18) in MFG were higher than in MSC and lower than in MG, fibroblast marker gene (vimentin) in MFG was significantly lower than in MG and MSC, milk protein genes (LALBA, BLG and CSN2) and milk fat synthesis-related genes (ACC, BTN1A1, FABP3 and FAS) in MFG were higher than in MG and MSC. In conclusion, the total RNA in MFG mainly derives from mammary epithelial cells and can be used to study the functional gene expression of mammary epithelial cells.

  14. Glucose and Fat Metabolism in Acromegaly: From Mice Models to Patient Care.

    Science.gov (United States)

    Dal, Jakob; List, Edward O; Jørgensen, Jens Otto L; Berryman, Darlene E

    2016-01-01

    Patients with active acromegaly are frequently insulin resistant, glucose intolerant, and at risk for developing overt type 2 diabetes. At the same time, these patients have a relatively lean phenotype associated with mobilization and oxidation of free fatty acids. These features are reversed by curative surgical removal of the growth hormone (GH)-producing adenoma. Mouse models of acromegaly share many of these characteristics, including a lean phenotype and proneness to type 2 diabetes. There are, however, also species differences with respect to oxidation rates of glucose and fat as well as the specific mechanisms underlying GH-induced insulin resistance. The impact of acromegaly treatment on insulin sensitivity and glucose tolerance depends on the treatment modality (e.g. somatostatin analogs also suppress insulin secretion, whereas the GH antagonist restores insulin sensitivity). The interplay between animal research and clinical studies has proven useful in the field of acromegaly and should be continued in order to understand the metabolic actions of GH. © 2015 S. Karger AG, Basel.

  15. Effects of Fortunella margarita fruit extract on metabolic disorders in high-fat diet-induced obese C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Si Tan

    Full Text Available INTRODUCTION: Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle fruit extract (FME on high-fat diet-induced C57BL/6 obese mice. METHODS: The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow, high-fat diet (HF, and high-fat diet with 1% (w/w extract of kumquat (HF+FME for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay. RESULTS: In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC, serum low density lipoprotein cholesterol (LDL-c levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG, serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes. CONCLUSION: Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances.

  16. Dietary thylakoids reduce visceral fat mass and increase expression of genes involved in intestinal fatty acid oxidation in high-fat fed rats.

    Science.gov (United States)

    Stenblom, Eva-Lena; Egecioglu, Emil; Montelius, Caroline; Ramachandran, Deepti; Bonn, Britta; Weström, Björn; Mansouri, Abdelhak; Langhans, Wolfgang; Erlanson-Albertsson, Charlotte

    2016-09-01

    Thylakoids reduce body weight gain and body fat accumulation in rodents. This study investigated whether an enhanced oxidation of dietary fat-derived fatty acids in the intestine contributes to the thylakoid effects. Male Sprague-Dawley rats were fed a high-fat diet with (n = 8) or without thylakoids (n = 8) for 2 wk. Body weight, food intake, and body fat were measured, and intestinal mucosa was collected and analyzed. Quantitative real-time PCR was used to measure gene expression levels of key enzymes involved in fatty acid transport, fatty acid oxidation, and ketogenesis. Another set of thylakoid-treated (n = 10) and control rats (n = 10) went through indirect calorimetry. In the first experiment, thylakoid-treated rats (n = 8) accumulated 25% less visceral fat than controls. Furthermore, fatty acid translocase (Fat/Cd36), carnitine palmitoyltransferase 1a (Cpt1a), and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) genes were upregulated in the jejunum of the thylakoid-treated group. In the second experiment, thylakoid-treated rats (n = 10) gained 17.5% less weight compared with controls and their respiratory quotient was lower, 0.86 compared with 0.91. Thylakoid-intake resulted in decreased food intake and did not cause steatorrhea. These results suggest that thylakoids stimulated intestinal fatty acid oxidation and ketogenesis, resulting in an increased ability of the intestine to handle dietary fat. The increased fatty acid oxidation and the resulting reduction in food intake may contribute to the reduced fat accumulation in thylakoid-treated animals. Copyright © 2016 the American Physiological Society.

  17. Associations of heart and adipocyte fatty acid-binding protein gene expression with intramuscular fat content in pigs

    NARCIS (Netherlands)

    Gerbens, F.; Verburg, F.J.; Moerkerk, van H.T.; Engel, B.; Buist, W.; Veerkamp, J.H.; Pas, te M.F.

    2001-01-01

    Intramuscular fat content is a major determinant of meat quality in pigs. Previously, polymorphisms in the adipocyte and heart fatty acid-binding protein genes, A-FABP and H-FABP, have been significantly associated with genetic variation of intramuscular fat content in a Duroc pig population.

  18. Associations of heart and adipocyte fatty acid-binding protein gene expression with intramuscular fat content in pigs.

    NARCIS (Netherlands)

    Gerbens, F.; Verburg, F.J.; Moerkerk, H.T.B. van; Engel, B.; Buist, W.; Veerkamp, J.H.; Pas, M.F. te

    2001-01-01

    Intramuscular fat content is a major determinant of meat quality in pigs. Previously, polymorphisms in the adipocyte and heart fatty acid-binding protein genes, A-FABP and H-FABP, have been significantly associated with genetic variation of intramuscular fat content in a Duroc pig population.

  19. Effect of dairy calcium or supplementary calcium intake on postprandial fat metabolism, appetite, and subsequent energy intake

    DEFF Research Database (Denmark)

    Lorenzen, J.K.; Nielsen, S.; Holst, J.J.

    2007-01-01

    Background: High calcium intake has been shown to increase fecal fat excretion. Objective: Our aim was to examine whether a high calcium intake from dairy products or from supplements affects postprandial fat metabolism and appetite through fat malabsorption. Design: Four different isocaloric meals...... postprandially. Results: Dairy calcium significantly diminished the postprandial lipid response. The baseline adjusted area under the curve for chylomicron triacylglycerol was approximate to 17% lower after the MC meal (P = 0.02) and approximate to 19% lower after the HC meal (P = 0.007) than after the LC meal...... and approximate to 15% lower after the MC meal (P = 0.0495) and approximate to 17% lower after the HC meal (P = 0.02) than after the Suppl meal. No consistent effects of calcium on appetite sensation, or on energy intake at the subsequent meal, or on the postprandial responses of cholecystokinin, glucagon...

  20. [Gene networks that regulate secondary metabolism in actinomycetes: pleiotropic regulators].

    Science.gov (United States)

    Rabyk, M V; Ostash, B O; Fedorenko, V O

    2014-01-01

    Current advances in the research and practical applications of pleiotropic regulatory genes for antibiotic production in actinomycetes are reviewed. The basic regulatory mechanisms found in these bacteria are outlined. Examples described in the review show the importance of the manipulation of regulatory systems that affect the synthesis of antibiotics for the metabolic engineering of the actinomycetes. Also, the study of these genes is the basis for the development of genetic engineering approaches towards the induction of "cryptic" part of the actinomycetes secondary metabolome, which capacity for production of biologically active compounds is much bigger than the diversity of antibiotics underpinned by traditional microbiological screening. Besides the practical problems, the study of regulatory genes for antibiotic biosynthesis will provide insights into the process of evolution of complex regulatory systems that coordinate the expression of gene operons, clusters and regulons, involved in the control of secondary metabolism and morphogenesis of actinomycetes.

  1. Radiation Exposure Alters Expression of Metabolic Enzyme Genes In Mice

    Science.gov (United States)

    Wotring, Virginia E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2010-01-01

    Most pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Because of the importance of the liver in drug metabolism it is important to understand the effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. This study is an effort to examine the effects of adaptive mechanisms that may be triggered by early exposure to low radiation doses. Using procedures approved by the JSC Animal Care & Use Committee, C57 male mice were exposed to Cs-137 in groups: controls, low dose (50 mGy), high dose (6Gy) and a fourth group that received both radiation doses separated by 24 hours. Animals were anesthetized and sacrificed 4 hours after their last radiation exposure. Livers were removed immediately and flash-frozen in liquid nitrogen. Tissue was homogenized, RNA extracted and purified (Absolutely RNA, Agilent). Quality of RNA samples was evaluated (Agilent Bioanalyzer 2100). Complementary DNA was prepared from high-quality RNA samples, and used to run RT-qPCR screening arrays for DNA Repair and Drug Metabolism (SuperArray, SABiosciences/Qiagen; BioRad Cfx96 qPCR System). Of 91 drug metabolism genes examined, expression of 7 was altered by at least one treatment condition. Genes that had elevated expression include those that metabolize promethazine and steroids (4-8-fold), many that reduce oxidation products, and one that reduces heavy metal exposure (greater than 200-fold). Of the 91 DNA repair and general metabolism genes examined, expression of 14 was altered by at least one treatment condition. These gene expression changes are likely homeostatic and could lead to development of new radioprotective countermeasures.

  2. Deregulation of the protocadherin gene FAT1 alters muscle shapes: implications for the pathogenesis of facioscapulohumeral dystrophy.

    Directory of Open Access Journals (Sweden)

    Nathalie Caruso

    2013-06-01

    Full Text Available Generation of skeletal muscles with forms adapted to their function is essential for normal movement. Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts. Constitutive inactivation of the protocadherin gene Fat1 uncoupled individual myoblast polarity within chains, altering the shape of selective groups of muscles in the shoulder and face. These shape abnormalities were followed by early onset regionalised muscle defects in adult Fat1-deficient mice. Tissue-specific ablation of Fat1 driven by Pax3-cre reproduced muscle shape defects in limb but not face muscles, indicating a cell-autonomous contribution of Fat1 in migrating muscle precursors. Strikingly, the topography of muscle abnormalities caused by Fat1 loss-of-function resembles that of human patients with facioscapulohumeral dystrophy (FSHD. FAT1 lies near the critical locus involved in causing FSHD, and Fat1 mutant mice also show retinal vasculopathy, mimicking another symptom of FSHD, and showed abnormal inner ear patterning, predictive of deafness, reminiscent of another burden of FSHD. Muscle-specific reduction of FAT1 expression and promoter silencing was observed in foetal FSHD1 cases. CGH array-based studies identified deletion polymorphisms within a putative regulatory enhancer of FAT1, predictive of tissue-specific depletion of FAT1 expression, which preferentially segregate with FSHD. Our study identifies FAT1 as a critical determinant of muscle form, misregulation of which associates with FSHD.

  3. Deregulation of the Protocadherin Gene FAT1 Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy

    Science.gov (United States)

    Caruso, Nathalie; Herberth, Balàzs; Bartoli, Marc; Puppo, Francesca; Dumonceaux, Julie; Zimmermann, Angela; Denadai, Simon; Lebossé, Marie; Roche, Stephane; Geng, Linda; Magdinier, Frederique; Attarian, Shahram; Bernard, Rafaelle; Maina, Flavio; Levy, Nicolas; Helmbacher, Françoise

    2013-01-01

    Generation of skeletal muscles with forms adapted to their function is essential for normal movement. Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts. Constitutive inactivation of the protocadherin gene Fat1 uncoupled individual myoblast polarity within chains, altering the shape of selective groups of muscles in the shoulder and face. These shape abnormalities were followed by early onset regionalised muscle defects in adult Fat1-deficient mice. Tissue-specific ablation of Fat1 driven by Pax3-cre reproduced muscle shape defects in limb but not face muscles, indicating a cell-autonomous contribution of Fat1 in migrating muscle precursors. Strikingly, the topography of muscle abnormalities caused by Fat1 loss-of-function resembles that of human patients with facioscapulohumeral dystrophy (FSHD). FAT1 lies near the critical locus involved in causing FSHD, and Fat1 mutant mice also show retinal vasculopathy, mimicking another symptom of FSHD, and showed abnormal inner ear patterning, predictive of deafness, reminiscent of another burden of FSHD. Muscle-specific reduction of FAT1 expression and promoter silencing was observed in foetal FSHD1 cases. CGH array-based studies identified deletion polymorphisms within a putative regulatory enhancer of FAT1, predictive of tissue-specific depletion of FAT1 expression, which preferentially segregate with FSHD. Our study identifies FAT1 as a critical determinant of muscle form, misregulation of which associates with FSHD. PMID:23785297

  4. Nutrient-gene interaction: metabolic genotype-phenotype relationship.

    Science.gov (United States)

    Go, Vay Liang W; Nguyen, Christine T H; Harris, Diane M; Lee, Wai-Nang Paul

    2005-12-01

    The U.S. Department of Health and Human Services (DHHS)/USDA Dietary Guidelines for Americans is a science and population evidence-based guide on diet and physical activity, providing advice and recommendations to promote a healthier lifestyle and reduce the risk of chronic diseases, including cancer. These recommendations are supported by the comprehensive evidence-based review on diet and cancer prevention conducted by the American Institute for Cancer Research, National Cancer Institute, World Health Organization/International Agency for Research on Cancer, and others. However, influencing dietary effects are the individual genetic predispositions that are the basis for considerable interindividual variations in cancer risk within the population and in nutrient homeostasis, which is maintained by genomic-nutrient and metabolic-phenotype interactions. Although genetics is an important component, it accounts for only a portion of this variation. An individual's overall phenotype, including health status, is achieved and maintained by the sum of metabolic activities functioning under differing circumstances within the life cycle and the complex interactions among genotype, metabolic phenotype, and the environment. In this postgenomic era, high-throughput groups of technologies in genomics, proteomics, and metabolomics measure and analyze DNA sequences, RNA transcripts, proteins, and nutrient-metabolic fluxes in a single experiment. These advances have transformed biomarker studies on nutrient-gene interactions from a reductionist concept into a holistic practice in which many regulated genes involved in metabolism, along with its metabolic phenotypes, can be measured through functional genomics and metabolic profiling. The overall integration of data and information from the building blocks of metabolism-based nutrient-gene interaction can lead to future individualized dietary recommendations to diminish cancer risk.

  5. Acute effects of monounsaturated fat on postprandial lipemia and gene expression in first-degree relatives of subjects with type 2 diabetes

    DEFF Research Database (Denmark)

    Holst, J J; Gregersen, S; Pedersen, S B

    2014-01-01

    a differential impact on incretin responses and on the expression of genes involved in carbohydrate and lipid metabolism in muscle and adipose tissues of REL and CON.Subjects/Methods:A total of 17 REL and 17 CON consumed a meal with 72 energy percent derived from MUFAs (macadamia nut oil). Plasma triglycerides...... have a differential impact on gene expression in muscle and adipose tissues in a pattern pointing toward early defects in lipid metabolism in REL.European Journal of Clinical Nutrition advance online publication, 14 May 2014; doi:10.1038/ejcn.2014.64.......Background/Objectives:Subjects with type 2 diabetes (T2D) and their nondiabetic first-degree relatives (REL) have increased risk of cardiovascular disease (CVD). Postprandial triglyceridemia (PPL), influenced by diet, is an independent risk factor for CVD. Dietary fat elicits increased PPL in T2D...

  6. A role for gene duplication and natural variation of gene expression in the evolution of metabolism.

    Directory of Open Access Journals (Sweden)

    Daniel J Kliebenstein

    Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.

  7. Kefir Peptides Prevent Hyperlipidemia and Obesity in High-Fat-Diet-Induced Obese Rats via Lipid Metabolism Modulation.

    Science.gov (United States)

    Tung, Yu-Tang; Chen, Hsiao-Ling; Wu, Hsin-Shan; Ho, Mei-Hsuan; Chong, Kowit-Yu; Chen, Chuan-Mu

    2018-02-01

    Obesity has reached epidemic proportions worldwide. Obesity is a complex metabolic disorder that is linked to numerous serious health complications with high morbidity. The present study evaluated the effects of kefir peptides on high fat diet (HFD)-induced obesity in rats. Kefir peptides markedly improved obesity, including body weight gain, inflammatory reactions and the formation of adipose tissue fat deposits around the epididymis and kidney, and adipocyte size. Treating high fat diet (HFD)-induced obese rats with kefir peptides significantly reduced the fatty acid synthase protein and increased the p-acetyl-CoA carboxylase protein to block lipogenesis in the livers. Kefir peptides also increased fatty acid oxidation by increasing the protein expressions of phosphorylated AMP-activated protein kinase, peroxisome proliferator-activated receptor-α, and hepatic carnitine palmitoyltransferase-1 in the livers. In addition, administration of kefir peptides significantly decreased the inflammatory response (TNF-α, IL-1β, and TGF-β) to modulate oxidative damage. These results demonstrate that kefir peptides treatment improves obesity via inhibition of lipogenesis, modulation of oxidative damage, and stimulation of lipid oxidation. Therefore, kefir peptides may act as an anti-obesity agent to prevent body fat accumulation and obesity-related metabolic diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. The Metabolic Implications of Glucocorticoids in a High-Fat Diet Setting and the Counter-Effects of Exercise

    Directory of Open Access Journals (Sweden)

    Emily C. Dunford

    2016-12-01

    Full Text Available Glucocorticoids (GCs are steroid hormones, naturally produced by activation of the hypothalamic-pituitary-adrenal (HPA axis, that mediate the immune and metabolic systems. Synthetic GCs are used to treat a number of inflammatory conditions and diseases including lupus and rheumatoid arthritis. Generally, chronic or high dose GC administration is associated with side effects such as steroid-induced skeletal muscle loss, visceral adiposity, and diabetes development. Patients who are taking exogenous GCs could also be more susceptible to poor food choices, but the effect that increasing fat consumption in combination with elevated exogenous GCs has only recently been investigated. Overall, these studies show that the damaging metabolic effects initiated through exogenous GC treatment are significantly amplified when combined with a high fat diet (HFD. Rodent studies of a HFD and elevated GCs demonstrate more glucose intolerance, hyperinsulinemia, visceral adiposity, and skeletal muscle lipid deposition when compared to rodents subjected to either treatment on its own. Exercise has recently been shown to be a viable therapeutic option for GC-treated, high-fat fed rodents, with the potential mechanisms still being examined. Clinically, these mechanistic studies underscore the importance of a low fat diet and increased physical activity levels when individuals are given a course of GC treatment.

  9. Oral and intestinal sweet and fat tasting: impact of receptor polymorphisms and dietary modulation for metabolic disease.

    Science.gov (United States)

    Cvijanovic, Nada; Feinle-Bisset, Christine; Young, Richard L; Little, Tanya J

    2015-05-01

    The human body has evolved with a disposition for nutrient storage, allowing for periods of irregular food availability and famine. In contrast, the modern diet is characterized by excessive consumption of fats and sugars, resulting in a surge in the rates of obesity and type 2 diabetes. Although these metabolic disorders arise from a complex interaction of genetic, social, and environmental factors, evidence now points to fundamental changes in nutrient metabolism at the cellular level contributing to the underlying pathology. Taste receptors detect nutrients in the oral cavity and gastrointestinal tract and can influence the hormonal response to nutrients; they may also become maladaptive in conditions of excess fat or sugar consumption. Precise links between taste receptor activity, and downstream effects on energy intake and glycemia are not well defined. This review outlines the candidate taste receptors for carbohydrates and fats in the oral cavity and within the small intestine, highlighting the contributions of underlying genetics (polymorphisms) and sensory challenges (e.g., a high-fat diet) to the development of obesity and type 2 diabetes. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Adaptations to climate in candidate genes for common metabolic disorders.

    Directory of Open Access Journals (Sweden)

    Angela M Hancock

    2008-02-01

    Full Text Available Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders.

  11. Effects of ferulic acid and γ-oryzanol on high-fat and high-fructose diet-induced metabolic syndrome in rats.

    Directory of Open Access Journals (Sweden)

    Ou Wang

    Full Text Available The high morbidity of metabolic dysfunction diseases has heightened interest in seeking natural and safe compounds to maintain optimal health. γ-Oryzanol (OZ, the ferulic acid (FA ester with phytosterols, mainly present in rice bran has been shown to improve markers of metabolic syndrome. This study investigates the effects of FA and OZ on alleviating high-fat and high-fructose diet (HFFD-induced metabolic syndrome parameters.Male SD rats were fed with a regular rodent diet, HFFD, or HFFD supplemented with 0.05% FA or 0.16% OZ (equimolar concentrations for 13 weeks. Food intake, organ indices, serum lipid profiles, glucose metabolism, insulin resistance (IR index and cytokine levels were analyzed. The mechanisms were further investigated in oleic acid-stimulated HepG2 cells by analyzing triglyceride (TG content and lipogenesis-related gene expressions.In the in vivo study, FA and OZ exhibited similar effects in alleviating HFFD-induced obesity, hyperlipidemia, hyperglycemia, and IR. However, only OZ treatment significantly decreased liver index and hepatic TG content, lowered serum levels of C-reactive protein and IL-6, and increased serum concentration of adiponectin. In the in vitro assay, only OZ administration significantly inhibited intracellular TG accumulation and down-regulated expression of stearoyl coenzyme-A desaturase-1, which might facilitate OZ to enhance its hepatoprotective effect.OZ is more effective than FA in inhibiting hepatic fat accumulation and inflammation. Thus, FA and OZ could be used as dietary supplements to alleviate the deleterious effects of HFFD.

  12. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men

    DEFF Research Database (Denmark)

    van der Beek, Christina M; Canfora, Emanuel E; Lenaerts, Kaatje

    2016-01-01

    . In this randomized, double-blind crossover trial, six overweight/obese men [body mass index (BMI) 25-35 kg/m(2)] underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions. A feeding catheter was endoscopically positioned at the beginning of each period and remained......Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men...

  13. Galectin-3 Deletion Enhances Visceral Adipose Tissue Inflammation and Dysregulates Glucose Metabolism in Mice on a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Jeftic Ilija

    2016-09-01

    Full Text Available Obesity and type 2 diabetes mellitus (T2DM constitute major health problems worldwide. Increased visceral adiposity enhances the risk of insulin resistance and type 2 diabetes. The mechanisms involved in obesity-associated chronic inflammation in metabolic tissues (metaflammation that lead to insulin resistance and dysregulated glucose metabolism are incompletely defined. Galectin-3 (Gal-3, a β-galactoside-binding lectin, modulates immune/inflammatory responses and specifically binds to metabolic danger molecules. To dissect the role of Gal-3 in obesity and diabetes, Gal-3-deficient (LGALS3-/- and wild-type (WT C57Bl/6 male mice were placed on a high-fat diet (HFD, 60% kcal fat or a standard chow diet (10% kcal fat for 6 months and metabolic, histological and immunophenotypical analyses of the visceral adipose tissue were performed. HFD-fed LGALS3-/- mice had higher body weights and more body weight gain, visceral adipose tissue (VAT, hyperglycaemia, hyperinsulinemia, insulin resistance and hyperlipidemia than diet-matched WT mice. Compared to WT mice, the enlarged VAT in obese LGALS3-/- mice contained larger adipocytes. Additionally, we demonstrate enhanced inflammation in the VAT of LGALS3-/- mice compared with diet-matched WT mice. The VAT of LGALS3-/- mice fed a HFD contained more numerous dendritic cells and proinflammatory F4/80+CD11c+CD11b+ and F4/80high macrophages. In contrast to WT mice, the numbers of CXCR3+ and CD8+ T cells were increased in the VAT of Gal-3-deficient mice after 6 months of high-fat feeding. We provide evidence that Gal-3 ablation results in enhanced HFD-induced adiposity, inflammation in the adipose tissue, insulin resistance and hyperglycaemia. Thus, Gal-3 represents an important regulator of obesity-associated immunometabolic alterations.

  14. The acute effects on duodenal gene expression in healthy men following consumption of a low-fat meal enriched with theobromine or fat

    NARCIS (Netherlands)

    Smolders, Lotte; Mensink, Ronald P.; Boekschoten, Mark V.; Ridder, De Rogier J.J.; Plat, Jogchum

    2018-01-01

    Increasing apoA-I synthesis may improve HDL functionality and lower CVD risk. As theobromine and fat increase fasting apoA-I concentrations, and the intestine is involved in apoA-I production, the acute effects of both were studied on duodenal gene transcription to better understand underlying

  15. Effects of rapeseed and soybean oil dietary supplementation on bovine fat metabolism, fatty acid composition and cholesterol levels in milk.

    Science.gov (United States)

    Altenhofer, Christian; Spornraft, Melanie; Kienberger, Hermine; Rychlik, Michael; Herrmann, Julia; Meyer, Heinrich H D; Viturro, Enrique

    2014-02-01

    The main goal of this experiment was to study the effect of milk fat depression, induced by supplementing diet with plant oils, on the bovine fat metabolism, with special interest in cholesterol levels. For this purpose 39 cows were divided in three groups and fed different rations: a control group (C) without any oil supplementation and two groups with soybean oil (SO) or rapeseed oil (RO) added to the partial mixed ration (PMR). A decrease in milk fat percentage was observed in both oil feedings with a higher decrease of -1·14 % with SO than RO with -0·98 % compared with the physiological (-0·15 %) decline in the C group. There was no significant change in protein and lactose yield. The daily milk cholesterol yield was lower in both oil rations than in control ration, while the blood cholesterol level showed an opposite variation. The milk fatty acid pattern showed a highly significant decrease of over 10 % in the amount of saturated fatty acids (SFA) in both oil feedings and a highly significant increase in mono (MUFA) and poly (PUFA) unsaturated fatty acids, conjugated linoleic acids (CLA) included. The results of this experiment suggest that the feeding of oil supplements has a high impact on milk fat composition and its significance for human health, by decreasing fats with a potentially negative effect (SFA and cholesterol) while simultaneously increasing others with positive (MUFA, PUFA, CLA).

  16. EPA prevents fat mass expansion and metabolic disturbances in mice fed with a Western diet[S

    Science.gov (United States)

    Pinel, Alexandre; Pitois, Elodie; Rigaudiere, Jean-Paul; Jouve, Chrystele; De Saint-Vincent, Sarah; Laillet, Brigitte; Montaurier, Christophe; Huertas, Alain; Morio, Beatrice; Capel, Frederic

    2016-01-01

    The impact of alpha linolenic acid (ALA), EPA, and DHA on obesity and metabolic complications was studied in mice fed a high-fat, high-sucrose (HF) diet. HF diets were supplemented with ALA, EPA, or DHA (1% w/w) and given to C57BL/6J mice for 16 weeks and to Ob/Ob mice for 6 weeks. In C57BL/6J mice, EPA reduced plasma cholesterol (−20%), limited fat mass accumulation (−23%) and adipose cell hypertrophy (−50%), and reduced plasma leptin concentration (−60%) compared with HF-fed mice. Furthermore, mice supplemented with EPA exhibited a higher insulin sensitivity (+24%) and glucose tolerance (+20%) compared with HF-fed mice. Similar effects were observed in EPA-supplemented Ob/Ob mice, although fat mass accumulation was not prevented. By contrast, in comparison with HF-fed mice, DHA did not prevent fat mass accumulation, increased plasma leptin concentration (+128%) in C57BL/6J mice, and did not improve glucose homeostasis in C57BL/6J and Ob/Ob mice. In 3T3-L1 adipocytes, DHA stimulated leptin expression whereas EPA induced adiponectin expression, suggesting that improved leptin/adiponectin balance may contribute to the protective effect of EPA. In conclusion, supplementation with EPA, but not ALA and DHA, could preserve glucose homeostasis in an obesogenic environment and limit fat mass accumulation in the early stage of weight gain. PMID:27307576

  17. Oral Fat Sensing and CD36 Gene Polymorphism in Algerian Lean and Obese Teenagers

    Directory of Open Access Journals (Sweden)

    Hadjer Daoudi

    2015-11-01

    Full Text Available Growing number of evidences have suggested that oral fat sensing, mediated by a glycoprotein CD36 (cluster of differentiation 36, plays a significant role in the development of obesity. Indeed, a decreased expression of CD36 in some obese subjects is associated with high dietary fat intake. In the present study, we examined whether an increase in body mass index (BMI is associated with altered oleic acid lingual detection thresholds and blood lipid profile in young Algerian teenagers (n = 165. The obese teenagers (n = 83; 14.01 ± 0.19 years; BMI z-score 2.67 ± 0.29 exhibited higher lingual detection threshold for oleic acid than lean participants (n = 82, 13.92 ± 0.23 years; BMI z-score 0.03 ± 0.0001. We also studied the association between rs1761667 polymorphism of CD36 gene and obesity. The AA and AG genotypes were more frequent in obese teenagers, whereas GG genotype was more common in lean participants. The A-allele frequency was higher in obese teenagers than that in lean children. We report that rs1761667 polymorphism of CD36 gene and oro-gustatory thresholds for fat might play a significant role in the development of obesity in young teenagers.

  18. Oral Fat Sensing and CD36 Gene Polymorphism in Algerian Lean and Obese Teenagers.

    Science.gov (United States)

    Daoudi, Hadjer; Plesník, Jiří; Sayed, Amira; Šerý, Omar; Rouabah, Abdelkader; Rouabah, Leila; Khan, Naim Akhtar

    2015-11-04

    Growing number of evidences have suggested that oral fat sensing, mediated by a glycoprotein CD36 (cluster of differentiation 36), plays a significant role in the development of obesity. Indeed, a decreased expression of CD36 in some obese subjects is associated with high dietary fat intake. In the present study, we examined whether an increase in body mass index (BMI) is associated with altered oleic acid lingual detection thresholds and blood lipid profile in young Algerian teenagers (n = 165). The obese teenagers (n = 83; 14.01 ± 0.19 years; BMI z-score 2.67 ± 0.29) exhibited higher lingual detection threshold for oleic acid than lean participants (n = 82, 13.92 ± 0.23 years; BMI z-score 0.03 ± 0.0001). We also studied the association between rs1761667 polymorphism of CD36 gene and obesity. The AA and AG genotypes were more frequent in obese teenagers, whereas GG genotype was more common in lean participants. The A-allele frequency was higher in obese teenagers than that in lean children. We report that rs1761667 polymorphism of CD36 gene and oro-gustatory thresholds for fat might play a significant role in the development of obesity in young teenagers.

  19. mRNA expression of genes regulating lipid metabolism in ringed seals (Pusa hispida) from differently polluted areas

    Energy Technology Data Exchange (ETDEWEB)

    Castelli, Martina Galatea [Norwegian Polar Institute, Fram Centre, 9296 Tromsø (Norway); University of Bergen, Department of Biology, 5020 Bergen (Norway); Rusten, Marte; Goksøyr, Anders [University of Bergen, Department of Biology, 5020 Bergen (Norway); Routti, Heli, E-mail: heli.routti@npolar.no [Norwegian Polar Institute, Fram Centre, 9296 Tromsø (Norway)

    2014-01-15

    Highlights: •Genes regulating lipid metabolism were studied in ringed seals. •We compared highly contaminated Baltic seals and less contaminated Svalbard seals. •mRNA expression of hepatic PPARγ was higher in the Baltic seals. •mRNA expression of adipose PPARγ target genes was higher in the Baltic seals. •Contaminant exposure may affect lipid metabolism in the Baltic ringed seals. -- Abstract: There is a growing concern about the ability of persistent organic pollutants (POPs) to influence lipid metabolism. Although POPs are found at high concentrations in some populations of marine mammals, for example in the ringed seal (Pusa hispida) from the Baltic Sea, little is known about the effects of POPs on their lipid metabolism. An optimal regulation of lipid metabolism is crucial for ringed seals during the fasting/molting season. This is a physiologically stressful period, during which they rely on the energy stored in their fat reserves. The mRNA expression levels for seven genes involved in lipid metabolism were analyzed in liver and/or blubber tissue from molting ringed seals from the polluted Baltic Sea and a less polluted reference location, Svalbard (Norway). mRNA expression of genes encoding peroxisome proliferator-activated receptors (PPAR) α and γ and their target genes acyl-coenzyme A oxidase 1 (ACOX1) and cluster of differentiation 36 (CD36) were analyzed in liver. mRNA expression level of genes encoding PPARβ, PPARγ and their target genes encoding fatty acid binding protein 4 (FABP4) and adiponectin (ADIPOQ) were measured in inner and middle blubber layers. In addition, we evaluated the influence of molting status on hepatic mRNA expression of genes encoding PPARs and their target genes in ringed seals from Svalbard. Our results show higher mRNA expression of genes encoding hepatic PPARγ and adipose PPARβ, FABP4, and ADIPOQ in the Baltic seals compared to the Svalbard seals. A positive relationship between mRNA expressions of genes

  20. mRNA expression of genes regulating lipid metabolism in ringed seals (Pusa hispida) from differently polluted areas

    International Nuclear Information System (INIS)

    Castelli, Martina Galatea; Rusten, Marte; Goksøyr, Anders; Routti, Heli

    2014-01-01

    Highlights: •Genes regulating lipid metabolism were studied in ringed seals. •We compared highly contaminated Baltic seals and less contaminated Svalbard seals. •mRNA expression of hepatic PPARγ was higher in the Baltic seals. •mRNA expression of adipose PPARγ target genes was higher in the Baltic seals. •Contaminant exposure may affect lipid metabolism in the Baltic ringed seals. -- Abstract: There is a growing concern about the ability of persistent organic pollutants (POPs) to influence lipid metabolism. Although POPs are found at high concentrations in some populations of marine mammals, for example in the ringed seal (Pusa hispida) from the Baltic Sea, little is known about the effects of POPs on their lipid metabolism. An optimal regulation of lipid metabolism is crucial for ringed seals during the fasting/molting season. This is a physiologically stressful period, during which they rely on the energy stored in their fat reserves. The mRNA expression levels for seven genes involved in lipid metabolism were analyzed in liver and/or blubber tissue from molting ringed seals from the polluted Baltic Sea and a less polluted reference location, Svalbard (Norway). mRNA expression of genes encoding peroxisome proliferator-activated receptors (PPAR) α and γ and their target genes acyl-coenzyme A oxidase 1 (ACOX1) and cluster of differentiation 36 (CD36) were analyzed in liver. mRNA expression level of genes encoding PPARβ, PPARγ and their target genes encoding fatty acid binding protein 4 (FABP4) and adiponectin (ADIPOQ) were measured in inner and middle blubber layers. In addition, we evaluated the influence of molting status on hepatic mRNA expression of genes encoding PPARs and their target genes in ringed seals from Svalbard. Our results show higher mRNA expression of genes encoding hepatic PPARγ and adipose PPARβ, FABP4, and ADIPOQ in the Baltic seals compared to the Svalbard seals. A positive relationship between mRNA expressions of genes

  1. Impact of a High-Fat or High-Fiber Diet on Intestinal Microbiota and Metabolic Markers in a Pig Model

    Directory of Open Access Journals (Sweden)

    Sonja N. Heinritz

    2016-05-01

    Full Text Available To further elaborate interactions between nutrition, gut microbiota and host health, an animal model to simulate changes in microbial composition and activity due to dietary changes similar to those in humans is needed. Therefore, the impact of two different diets on cecal and colonic microbial gene copies and metabolic activity, organ development and biochemical parameters in blood serum was investigated using a pig model. Four pigs were either fed a low-fat/high-fiber (LF, or a high-fat/low-fiber (HF diet for seven weeks, with both diets being isocaloric. A hypotrophic effect of the HF diet on digestive organs could be observed compared to the LF diet (p < 0.05. Higher gene copy numbers of Bacteroides (p < 0.05 and Enterobacteriaceae (p < 0.001 were present in intestinal contents of HF pigs, bifidobacteria were more abundant in LF pigs (p < 0.05. Concentrations of acetate and butyrate were higher in LF pigs (p < 0.05. Glucose was higher in HF pigs, while glutamic pyruvic transaminase (GPT showed higher concentrations upon feeding the LF diet (p < 0.001. However, C-reactive protein (CRP decreased with time in LF pigs (p < 0.05. In part, these findings correspond to those in humans, and are in support of the concept of using the pig as human model.

  2. Maternal high-fat-diet programs rat offspring liver fatty acid metabolism.

    Science.gov (United States)

    Seet, Emily L; Yee, Jennifer K; Jellyman, Juanita K; Han, Guang; Ross, Michael G; Desai, Mina

    2015-06-01

    In offspring exposed in utero to a maternal diet high in fat (HF), we have previously demonstrated that despite similar birth weights, HF adult offspring at 6 months of age had significantly higher body weights, greater adiposity, and increased triacylglycerol (TAG) levels as compared to controls. We hypothesized that a maternal HF diet predisposes to offspring adiposity via a programmed increase in the synthesis of monounsaturated fatty acids in the liver and hence increased substrate availability for liver TAG synthesis. We further hypothesized that programmed changes in offspring liver fatty acid metabolism are associated with increased liver expression of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1). Female rats were maintained on a HF diet rich in monounsaturated fatty acids (MUFA) prior to and throughout pregnancy and lactation. After birth, newborns were nursed by the same dam, and all offspring were weaned to control diet. Plasma and liver fatty acid compositions were determined using gas chromatography/mass spectrometry. Fatty acid C16 desaturation indices of palmitoleic/palmitic and (vaccenic + palmitoleic)/palmitic and the C18 desaturation index of oleic/stearic were calculated. Liver protein abundance of SCD-1 was analyzed in newborns and adult offspring. Plasma and liver C16 desaturation indices were decreased in HF newborns, but increased in the adult offspring. Liver SCD-1 expression was increased in the HF adult offspring. These data show that the maternal HF diet during pregnancy and lactation increases offspring liver SCD-1 protein abundance and alters the liver C16 desaturase pathway.

  3. Determinants of human adipose tissue gene expression: impact of diet, sex, metabolic status, and cis genetic regulation.

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    Nathalie Viguerie

    2012-09-01

    Full Text Available Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification of environmental and individual factors controlling AT adaptation is therefore essential. Here, expression of 271 transcripts, selected for regulation according to obesity and weight changes, was determined in 515 individuals before, after 8-week low-calorie diet-induced weight loss, and after 26-week ad libitum weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently controlled AT gene expression. These analyses help understanding the relative importance of environmental and individual factors that control the expression of human AT genes and therefore may foster strategies aimed at improving AT function in metabolic diseases.

  4. The intake of high-fat diets induces an obesogenic-like gene expression profile in peripheral blood mononuclear cells, which is reverted by dieting.

    Science.gov (United States)

    Reynés, Bàrbara; García-Ruiz, Estefanía; Palou, Andreu; Oliver, Paula

    2016-06-01

    Peripheral blood mononuclear cells (PBMC) are increasingly used for nutrigenomic studies. In this study, we aimed to identify whether these cells could reflect the development of an obesogenic profile associated with the intake of high-fat (HF) diets. We analysed, by real-time RT-PCR, the dietary response of key genes related to lipid metabolism, obesity and inflammation in PBMC of control rats, rats fed a cafeteria or a commercial HF diet and rats fed a control diet after the intake of a cafeteria diet (post-cafeteria model). Cafeteria diet intake, which resulted in important overweight and related complications, altered the expressions of most of the studied genes in PBMC, evidencing the development of an obesogenic profile. Commercial HF diet, which produced metabolic alterations but in the absence of noticeably increased body weight, also altered PBMC gene expression, inducing a similar regulatory pattern as that observed for the cafeteria diet. Regulation of carnitine palmitoyltransferase I (Cpt1a) mRNA expression was of special interest; its expression reflected metabolic alterations related to the intake of both obesogenic diets (independently of increased body weight) even at an early stage as well as metabolic recovery in post-cafeteria animals. Thus, PBMC constitute an important source of biomarkers that reflect the increased adiposity and metabolic deregulation associated with the intake of HF diets. In particular, we propose an analysis of Cpt1a expression as a good biomarker to detect the early metabolic alterations caused by the consumption of hyperlipidic diets, and also as a marker of metabolic recovery associated to weight loss.

  5. An integrative transcriptomic approach to identify depot differences in genes and microRNAs in adipose tissues from high fat fed mice

    Science.gov (United States)

    Wijayatunga, Nadeeja N.; Pahlavani, Mandana; Kalupahana, Nishan S.; Kottapalli, Kameswara Rao; Gunaratne, Preethi H.; Coarfa, Cristian; Ramalingam, Latha; Moustaid-Moussa, Naima

    2018-01-01

    Obesity contributes to metabolic disorders such as diabetes and cardiovascular disease. Characterization of differences between the main adipose tissue depots, white (WAT) [including subcutaneous (SAT) and visceral adipose tissue (VAT)] and brown adipose tissue (BAT) helps to identify their roles in obesity. Thus, we studied depot-specific differences in whole transcriptome and miRNA profiles of SAT, VAT and BAT from high fat diet (HFD/45% of calories from fat) fed mice using RNA sequencing and small RNA-Seq. Using quantitative real-time polymerase chain reaction, we validated depot-specific differences in endoplasmic reticulum (ER) stress related genes and miRNAs using mice fed a HFD vs. low fat diet (LFD/10% of calories from fat). According to the transcriptomic analysis, lipogenesis, adipogenesis, inflammation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were higher in VAT compared to BAT, whereas energy expenditure, fatty acid oxidation and oxidative phosphorylation were higher in BAT than in VAT of the HFD fed mice. In contrast to BAT, ER stress marker genes were significantly upregulated in VAT of HFD fed mice than the LFD fed mice. For the first time, we report depot specific differences in ER stress related miRNAs including; downregulation of miR-125b-5p, upregulation miR-143-3p, and miR-222-3p in VAT following HFD and upregulation of miR-30c-2-3p only in BAT following a HFD in mice than the LFD mice. In conclusion, HFD differentially regulates miRNAs and genes in different adipose depots with significant induction of genes related to lipogenesis, adipogenesis, inflammation, ER stress, and UPR in WAT compared to BAT. PMID:29507687

  6. Ferulic Acid Alleviates Changes in a Rat Model of Metabolic Syndrome Induced by High-Carbohydrate, High-Fat Diet

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    Ketmanee Senaphan

    2015-08-01

    Full Text Available Metabolic syndrome is a cluster of metabolic abnormalities characterized by obesity, insulin resistance, hypertension and dyslipidemia. Ferulic acid (FA is the major phenolic compound found in rice oil and various fruits and vegetables. In this study, we examined the beneficial effects of FA in minimizing insulin resistance, vascular dysfunction and remodeling in a rat model of high-carbohydrate, high-fat diet-induced metabolic changes, which is regarded as an analogue of metabolic syndrome (MS in man. Male Sprague-Dawley rats were fed a high carbohydrate, high fat (HCHF diet and 15% fructose in drinking water for 16 weeks, where control rats were fed with standard chow diet and tap water. FA (30 or 60 mg/kg was orally administered to the HCHF and control rats during the last six weeks of the study. We observed that FA significantly improved insulin sensitivity and lipid profiles, and reduced elevated blood pressure, compared to untreated controls (p < 0.05. Moreover, FA also improved vascular function and prevented vascular remodeling of mesenteric arteries. The effects of FA in HCHF-induced MS may be realized through suppression of oxidative stress by down-regulation of p47phox, increased nitric oxide (NO bioavailability with up-regulation of endothelial nitric oxide synthase (eNOS and suppression of tumor necrosis factor-α (TNF-α. Our results suggest that supplementation of FA may have health benefits by minimizing the cardiovascular complications of MS and alleviating its symptoms.

  7. High-fat diets exaggerate endocrine and metabolic phenotypes in a rat model of DHEA-induced PCOS.

    Science.gov (United States)

    Zhang, Haolin; Yi, Ming; Zhang, Yan; Jin, Hongyan; Zhang, Wenxin; Yang, Jingjing; Yan, Liying; Li, Rong; Zhao, Yue; Qiao, Jie

    2016-04-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder with unclear etiology and unsatisfactory management. Effects of diets on the phenotype of PCOS were not fully understood. In the present study, we applied 45 and 60% high-fat diets (HFDs) on a rat model of PCOS induced by postnatal DHEA injection. We found that both DHEA and DHEA+HFDs rats exhibited reproductive abnormalities, including hyperandrogenism, irregular cycles and polycystic ovaries. The addition of HFDs, especially 60% HFDs, exaggerated morphological changes of ovaries and a number of metabolic changes, including increased body weight and body fat content, impaired glucose tolerance and increased serum insulin levels. Results from qPCR showed that DHEA-induced increased expression of hypothalamic androgen receptor and LH receptor were reversed by the addition of 60% HFDs. In contrast, the ovarian expression of LH receptor and insulin receptor mRNA was upregulated only with the addition of 60% HFDs. These findings indicated that DHEA and DHEA+HFDs might influence PCOS phenotypes through distinct mechanisms: DHEA affects the normal function of hypothalamus-pituitary-ovarian axis through LH, whereas the addition of HFDs exaggerated endocrine and metabolic dysfunction through ovarian responses to insulin-related mechanisms. We concluded that the addition of HFDs yielded distinct phenotypes of DHEA-induced PCOS and could be used for studies on both reproductive and metabolic features of the syndrome. © 2016 Society for Reproduction and Fertility.

  8. Spirulina improves non-alcoholic steatohepatitis, visceral fat macrophage aggregation, and serum leptin in a mouse model of metabolic syndrome.

    Science.gov (United States)

    Fujimoto, Makoto; Tsuneyama, Koichi; Fujimoto, Takako; Selmi, Carlo; Gershwin, M Eric; Shimada, Yutaka

    2012-09-01

    Nutritional approaches are sought to overcome the limits of pioglitazone in metabolic syndrome and non-alcoholic fatty liver disease. Spirulina, a filamentous unicellular alga, reduces serum lipids and blood pressure while exerting antioxidant effects. To determine whether Spirulina may impact macrophages infiltrating the visceral fat in obesity characterizing our metabolic syndrome mouse model induced by the subcutaneous injection treatment of monosodium glutamate. Mice were randomized to receive standard food added with 5% Spirulina, 0.02% pioglitazone, or neither. We tested multiple biochemistry and histology (both liver and visceral fat) readouts at 24 weeks of age. Data demonstrate that both the Spirulina and the pioglitazone groups had significantly lower serum cholesterol and triglyceride levels and liver non-esterified fatty acid compared to untreated mice. Spirulina and pioglitazone were associated with significantly lower leptin and higher levels, respectively, compared to the control group. At liver histology, non-alcoholic fatty liver disease activity score and lipid peroxide were significantly lower in mice treated with Spirulina. Spirulina reduces dyslipidaemia in our metabolic syndrome model while ameliorating visceral adipose tissue macrophages. Human studies are needed to determine whether this safe supplement could prove beneficial in patients with metabolic syndrome. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  9. Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

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    Rubén Díaz-Rúa

    2016-11-01

    Full Text Available Background: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC is a promising tool to identify subjects at risk of developing diet-related diseases. Objective: We analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF and high-protein (HP diets. Design: We administered HF and HP diets (4 months to adult Wistar rats in isocaloric conditions to a control diet, mainly to avoid overweight associated with the intake of hyperlipidic diets and, thus, to be able to characterise markers of metabolically obese normal-weight (MONW syndrome. PBMC samples were collected at different time points of dietary treatment and expression of relevant energy homeostatic genes analysed by real-time reverse transcription-polymerase chain reaction. Serum parameters related with metabolic syndrome, as well as fat deposition in liver, were also analysed. Results: The most outstanding results were those obtained for the expression of the lipolytic gene carnitine palmitoyltransferase 1a (Cpt1a. Cpt1a expression in PBMC increased after only 1 month of exposure to both unbalanced diets, and this increased expression was maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a expression was altered even in the absence of increased body weight but correlated with alterations such as higher insulin resistance, alteration of serum lipid profile and, particularly, increased fat deposition in liver, a feature characteristic of metabolic syndrome, which was even observed in animals fed with HP diet. Conclusions: We propose Cpt1a gene expression analysis in PBMC as an early biomarker of metabolic alterations associated with MONW phenotype due to the intake of isocaloric HF diets, as

  10. Dietary fat type, meat quality and fatty acid metabolism in swine

    NARCIS (Netherlands)

    Mitchaothai, J.

    2007-01-01

    This thesis focuses on the replacement of animal fat by vegetable oil in the diet for growing-finishing pigs. Generally, but not exclusively, fats of animal origin contain higher proportions of saturated fatty acids (SFA) than vegetable oils that are commonly rich in polyunsaturated fatty acids

  11. Metabolism and Whole-Body Fat Oxidation Following Post-Exercise Carbohydrate or Protein Intake

    DEFF Research Database (Denmark)

    Hall, Ulrika Andersson; Pettersson, Stefan; Edin, Fredrik

    2018-01-01

    : Protein supplementation immediately post-exercise did not affect the doubling in whole body fat oxidation seen during a subsequent exercise trial 2 hours later. Neither did it affect resting fat oxidation during the post-exercise period despite increased insulin levels and attenuated ketosis. Carbohydrate...

  12. Effect of dietary fat sources on fatty acid deposition and lipid metabolism in broiler chickens

    NARCIS (Netherlands)

    Smink, W.; Gerrits, W.J.J.; Hovenier, R.; Geelen, M.J.H.; Verstegen, M.W.A.; Beynen, A.C.

    2010-01-01

    The hypothesis tested was that dietary vegetable fats rich in saturated fatty acids, when compared with a vegetable oil rich in linoleic acid, increase fat deposition in broiler chickens and affect synthesis or oxidation, or both, of individual fatty acids. Diets with native sunflower oil (SO), a

  13. A genome wide association study for backfat thickness in Italian Large White pigs highlights new regions affecting fat deposition including neuronal genes

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    Fontanesi Luca

    2012-11-01

    Full Text Available Abstract Background Carcass fatness is an important trait in most pig breeding programs. Following market requests, breeding plans for fresh pork consumption are usually designed to reduce carcass fat content and increase lean meat deposition. However, the Italian pig industry is mainly devoted to the production of Protected Designation of Origin dry cured hams: pigs are slaughtered at around 160 kg of live weight and the breeding goal aims at maintaining fat coverage, measured as backfat thickness to avoid excessive desiccation of the hams. This objective has shaped the genetic pool of Italian heavy pig breeds for a few decades. In this study we applied a selective genotyping approach within a population of ~ 12,000 performance tested Italian Large White pigs. Within this population, we selectively genotyped 304 pigs with extreme and divergent backfat thickness estimated breeding value by the Illumina PorcineSNP60 BeadChip and performed a genome wide association study to identify loci associated to this trait. Results We identified 4 single nucleotide polymorphisms with P≤5.0E-07 and additional 119 ones with 5.0E-07 Conclusions Further investigations are needed to evaluate the effects of the identified single nucleotide polymorphisms associated with backfat thickness on other traits as a pre-requisite for practical applications in breeding programs. Reported results could improve our understanding of the biology of fat metabolism and deposition that could also be relevant for other mammalian species including humans, confirming the role of neuronal genes on obesity.

  14. Porcine Is a Positional Candidate Gene Associated with Growth and Fat Deposition

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    Bong Hwan Choi

    2012-12-01

    Full Text Available Crosses between Korean and Landrace pigs have revealed a large quantitative trait loci (QTL region for fat deposition in a region (89 cM of porcine chromosome 4 (SSC4. To more finely map this QTL region and identify candidate genes for this trait, comparative mapping of pig and human chromosomes was performed in the present study. A region in the human genome that corresponds to the porcine QTL region was identified in HSA1q21. Furthermore, the LMNA gene, which is tightly associated with fat augmentation in humans, was localized to this region. Radiation hybrid (RH mapping using a Sus scrofa RH panel localized LMNA to a region of 90.3 cM in the porcine genome, distinct from microsatellite marker S0214 (87.3 cM. Two-point analysis showed that LMNA was linked to S0214, SW1996, and S0073 on SSC4 with logarithm (base 10 of odds scores of 20.98, 17.78, and 16.73, respectively. To clone the porcine LMNA gene and to delineate the genomic structure and sequences, including the 3′untranslated region (UTR, rapid amplification of cDNA ends was performed. The coding sequence of porcine LMNA consisted of 1,719 bp, flanked by a 5’UTR and a 3’UTR. Two synonymous single nucleotide polymorphisms (SNPs were identified in exons 3 and 7. Association tests showed that the SNP located in exon 3 (A193A was significantly associated with weight at 30 wks (p<0.01 and crude fat content (p<0.05. This association suggests that SNPs located in LMNA could be used for marker-assisted selection in pigs.

  15. Obesity induced by a pair-fed high fat sucrose diet: methylation and expression pattern of genes related to energy homeostasis

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    Campión Javier

    2010-06-01

    Full Text Available Abstract Background The expression of some genes controlling energy homeostasis could be regulated by epigenetic mechanisms that may play a role in body weight regulation. Thus, it is known that various nutritional factors affect DNA methylation. In order to assess whether the macronutrient composition of the diet could be related to the epigenetic regulation of gene expression and with obesity development, we investigated the effects on methylation and expression patterns of two pair-fed isocaloric diets in rats: control (rich in starch and HFS (rich in fat and sucrose. Results The pair-fed HFS diet induced higher weight gain and adiposity as compared to the controls as well as liver triglyceride accumulation and oxidative stress. Feeding the HFS diet impaired glucose tolerance and serum triglycerides and cholesterol. Liver glucokinase expression, a key glycolytic gene, remained unaltered, as well as the mRNA values of fatty acid synthase and NADH dehydrogenase (ubiquinone 1 beta subcomplex, 6 (NDUFB6 in liver and visceral adipocytes, which regulate lipogenesis and mitochondrial oxidative metabolism, respectively. Liver expression of hydroxyacyl-coenzyme A dehydrogenase (HADHB, a key gene of β-oxidation pathway, was higher in the HFS-fed animals. However, the methylation status of CpG islands in HADHB and glucokinase genes remained unchanged after feeding the HFS diet. Conclusions These results confirm that the distribution and type of macronutrients (starch vs. sucrose, and percent of fat influence obesity onset and the associated metabolic complications. HFS diets produce obesity independently of total energy intake, although apparently no epigenetic (DNA methylation changes accompanied the modifications observed in gene expression.

  16. Gustatory perception and fat body energy metabolism are jointly affected by vitellogenin and juvenile hormone in honey bees.

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    Ying Wang

    2012-06-01

    Full Text Available Honey bees (Apis mellifera provide a system for studying social and food-related behavior. A caste of workers performs age-related tasks: young bees (nurses usually feed the brood and other adult bees inside the nest, while older bees (foragers forage outside for pollen, a protein/lipid source, or nectar, a carbohydrate source. The workers' transition from nursing to foraging and their foraging preferences correlate with differences in gustatory perception, metabolic gene expression, and endocrine physiology including the endocrine factors vitellogenin (Vg and juvenile hormone (JH. However, the understanding of connections among social behavior, energy metabolism, and endocrine factors is incomplete. We used RNA interference (RNAi to perturb the gene network of Vg and JH to learn more about these connections through effects on gustation, gene transcripts, and physiology. The RNAi perturbation was achieved by single and double knockdown of the genes ultraspiracle (usp and vg, which encode a putative JH receptor and Vg, respectively. The double knockdown enhanced gustatory perception and elevated hemolymph glucose, trehalose, and JH. We also observed transcriptional responses in insulin like peptide 1 (ilp1, the adipokinetic hormone receptor (AKHR, and cGMP-dependent protein kinase (PKG, or "foraging gene" Amfor. Our study demonstrates that the Vg-JH regulatory module controls changes in carbohydrate metabolism, but not lipid metabolism, when worker bees shift from nursing to foraging. The module is also placed upstream of ilp1, AKHR, and PKG for the first time. As insulin, adipokinetic hormone (AKH, and PKG pathways influence metabolism and gustation in many animals, we propose that honey bees have conserved pathways in carbohydrate metabolism and conserved connections between energy metabolism and gustatory perception. Thus, perhaps the bee can make general contributions to the understanding of food-related behavior and metabolic disorders.

  17. Gustatory perception and fat body energy metabolism are jointly affected by vitellogenin and juvenile hormone in honey bees.

    Science.gov (United States)

    Wang, Ying; Brent, Colin S; Fennern, Erin; Amdam, Gro V

    2012-06-01

    Honey bees (Apis mellifera) provide a system for studying social and food-related behavior. A caste of workers performs age-related tasks: young bees (nurses) usually feed the brood and other adult bees inside the nest, while older bees (foragers) forage outside for pollen, a protein/lipid source, or nectar, a carbohydrate source. The workers' transition from nursing to foraging and their foraging preferences correlate with differences in gustatory perception, metabolic gene expression, and endocrine physiology including the endocrine factors vitellogenin (Vg) and juvenile hormone (JH). However, the understanding of connections among social behavior, energy metabolism, and endocrine factors is incomplete. We used RNA interference (RNAi) to perturb the gene network of Vg and JH to learn more about these connections through effects on gustation, gene transcripts, and physiology. The RNAi perturbation was achieved by single and double knockdown of the genes ultraspiracle (usp) and vg, which encode a putative JH receptor and Vg, respectively. The double knockdown enhanced gustatory perception and elevated hemolymph glucose, trehalose, and JH. We also observed transcriptional responses in insulin like peptide 1 (ilp1), the adipokinetic hormone receptor (AKHR), and cGMP-dependent protein kinase (PKG, or "foraging gene" Amfor). Our study demonstrates that the Vg-JH regulatory module controls changes in carbohydrate metabolism, but not lipid metabolism, when worker bees shift from nursing to foraging. The module is also placed upstream of ilp1, AKHR, and PKG for the first time. As insulin, adipokinetic hormone (AKH), and PKG pathways influence metabolism and gustation in many animals, we propose that honey bees have conserved pathways in carbohydrate metabolism and conserved connections between energy metabolism and gustatory perception. Thus, perhaps the bee can make general contributions to the understanding of food-related behavior and metabolic disorders.

  18. Digestive and metabolic utilization of lauric, myristic and stearic acid in cows, and associated effects on milk fat quality.

    Science.gov (United States)

    Dohme, Frigga; Machmüller, Andrea; Sutter, F; Kreuzer, M

    2004-04-01

    In an experiment with 3 x 6 Brown Swiss cows, the effects of dietary supplementations (40 g/kg) of non-esterified lauric (12 : 0), myristic (14 : 0) and stearic acid (18 : 0) on digestibility, metabolisability, milk fat composition and melting properties were investigated. The diet consisted of forage and concentrate in a ratio of 3 : 2. Cows were fed the C18 : 0 supplemented diet for 10 days before treatment feeding started for a 15-day experimental period where, at the end, excreta were quantitatively collected and gaseous exchange was measured. The DM intake averaged 17.9 kg/d for the C14 : 0 and C18 : 0 diets and was reduced (P acid supplementation were clearly reflected in the milk fat composition. Associated changes were elevated CLA and C18 : 1 trans when supplementing C12 : 0, and a high C18 : 1 to C16 : 0 ratio (P < 0.05) in the C12 : 0and C18 : 0 groups which resulted in an easier melting milk fat than with supplementary C14 : 0. Despite certain favourable effects of C12 : 0 in metabolic energy utilization and milk fat melting properties (relative to C14 : 0), more research is needed on how to improve its palatability for dairy cows.

  19. The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism.

    Science.gov (United States)

    von Loeffelholz, Christian; Lieske, Stefanie; Neuschäfer-Rube, Frank; Willmes, Diana M; Raschzok, Nathanael; Sauer, Igor M; König, Jörg; Fromm, Martin F; Horn, Paul; Chatzigeorgiou, Antonios; Pathe-Neuschäfer-Rube, Andrea; Jordan, Jens; Pfeiffer, Andreas F H; Mingrone, Geltrude; Bornstein, Stefan R; Stroehle, Peter; Harms, Christoph; Wunderlich, F Thomas; Helfand, Stephen L; Bernier, Michel; de Cabo, Rafael; Shulman, Gerald I; Chavakis, Triantafyllos; Püschel, Gerhard P; Birkenfeld, Andreas L

    2017-08-01

    Reduced expression of the Indy ("I am Not Dead, Yet") gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane-associated citrate transporter expressed highly in the liver, protects mice from high-fat diet-induced and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We studied a possible role of mIndy in human hepatic fat metabolism. In obese, insulin-resistant patients with nonalcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In nonhuman primates, a 2-year high-fat, high-sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription through the IL-6 receptor and activation of the transcription factor signal transducer and activator of transcription 3, and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-signal transducer and activator of transcription 3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx, and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and nonhuman primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 through mINDY. Targeting human mINDY may have therapeutic potential in obese patients with nonalcoholic fatty liver disease. German Clinical

  20. Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise

    DEFF Research Database (Denmark)

    Pilegaard, Henriette; Osada, Takuya; Andersen, Lisbeth Tingsted

    2005-01-01

    In skeletal muscle of humans, transcription of several metabolic genes is transiently induced during recovery from exercise when no food is consumed. To determine the potential influence of substrate availability on the transcriptional regulation of metabolic genes during recovery from exercise, 9...... the transcriptional regulation of metabolic genes in skeletal muscle of humans during recovery from exercise....

  1. Obesity, the metabolic syndrome, and type 2 diabetes in developing countries: role of dietary fats and oils.

    Science.gov (United States)

    Misra, Anoop; Singhal, Neha; Khurana, Lokesh

    2010-06-01

    Developing countries are undergoing rapid nutrition transition concurrent with increases in obesity, the metabolic syndrome, and type 2 diabetes mellitus (T2DM). From a healthy traditional high-fiber, low-fat, low-calorie diet, a shift is occurring toward increasing consumption of calorie-dense foods containing refined carbohydrates, fats, red meats, and low fiber. Data show an increase in the supply of animal fats and increased intake of saturated fatty acid (SFAs) (obtained from coconut oil, palm oil, and ghee [clarified butter]) in many developing countries, particularly in South Asia and South-East Asia. In some South Asian populations, particularly among vegetarians, intake of n-3 polyunsaturated fatty acids (PUFAs) (obtained from flaxseed, mustard, and canola oils) and long-chain (LC) n-3 PUFAs (obtained from fish and fish oils) is low. Further, the effect of supplementation of n-3 PUFAs on metabolic risk factors and insulin resistance, except for demonstrated benefit in terms of decreased triglycerides, needs further investigation among South Asians. Data also show that intake of monounsaturated fatty acids (MUFAs) ranged from 4.7% to 16.4%en in developing countries, and supplementing it from olive, canola, mustard, groundnut, and rice bran oils may reduce metabolic risk. In addition, in some developing countries, intake of n-6 PUFAs (obtained from sunflower, safflower, corn, soybean, and sesame oils) and trans-fatty acids (TFAs) is increasing. These data show imbalanced consumption of fats and oils in developing countries, which may have potentially deleterious metabolic and glycemic consequences, although more research is needed. In view of the rapid rise of T2DM in developing countries, more aggressive public health awareness programs coupled with governmental action and clear country-specific guidelines are required, so as to promote widespread use of healthy oils, thus curbing intake of SFAs and TFAs, and increasing intake of n-3 PUFAs and MUFAs. Such

  2. Functional Comparison for Lipid Metabolism and Intestinal and Fecal Microflora Enzyme Activities between Low Molecular Weight Chitosan and Chitosan Oligosaccharide in High-Fat-Diet-Fed Rats.

    Science.gov (United States)

    Chiu, Chen-Yuan; Feng, Shih-An; Liu, Shing-Hwa; Chiang, Meng-Tsan

    2017-07-24

    The present study investigated and compared the regulatory effects on the lipid-related metabolism and intestinal disaccharidase/fecal bacterial enzyme activities between low molecular weight chitosan and chitosan oligosaccharide in high-fat-diet-fed rats. Diet supplementation of low molecular weight chitosan showed greater efficiency than chitosan oligosaccharide in suppressing the increased weights in body and in liver and adipose tissues of high-fat-diet-fed rats. Supplementation of low molecular weight chitosan also showed a greater improvement than chitosan oligosaccharide in imbalance of plasma, hepatic, and fecal lipid profiles, and intestinal disaccharidase activities in high-fat-diet-fed rats. Moreover, both low molecular weight chitosan and chitosan oligosaccharide significantly decreased the fecal microflora mucinase and β-glucuronidase activities in high-fat-diet-fed rats. These results suggest that low molecular weight chitosan exerts a greater positive improvement than chitosan oligosaccharide in lipid metabolism and intestinal disaccharidase activity in high-fat-diet-induced obese rats.

  3. Effect of high-fat diets on body composition, lipid metabolism and insulin sensitivity, and the role of exercise on these parameters

    Directory of Open Access Journals (Sweden)

    D.F. Coelho

    2011-10-01

    Full Text Available Dietary fat composition can interfere in the development of obesity due to the specific roles of some fatty acids that have different metabolic activities, which can alter both fat oxidation and deposition rates, resulting in changes in body weight and/or composition. High-fat diets in general are associated with hyperphagia, but the type of dietary fat seems to be more important since saturated fats are linked to a positive fat balance and omental adipose tissue accumulation when compared to other types of fat, while polyunsaturated fats, omega-3 and omega-6, seem to increase energy expenditure and decrease energy intake by specific mechanisms involving hormone-sensitive lipase, activation of peroxisome proliferator-activated receptor α (PPARα and others. Saturated fat intake can also impair insulin sensitivity compared to omega-3 fat, which has the opposite effect due to alterations in cell membranes. Obesity is also associated with impaired mitochondrial function. Fat excess favors the production of malonyl-CoA, which reduces GLUT4 efficiency. The tricarboxylic acid cycle and beta-oxidation are temporarily uncoupled, forming metabolite byproducts that augment reactive oxygen species production. Exercise can restore mitochondrial function and insulin sensitivity, which may be crucial for a better prognosis in treating or preventing obesity.

  4. Modulation of Gene Expression in Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells in Osteoarthritis.

    Science.gov (United States)

    Bravo, Beatriz; Argüello, Jose Manuel; Gortazar, Arancha R; Forriol, Francisco; Vaquero, Javier

    2018-01-01

    Aim In the osteoarthritis (OA) disease, all structures of the joint are involved. The infrapatellar Hoffa fat pad is rich in macrophages and granulocytes, which also represents a source of adipose mesenchymal progenitor cells (ASC) cells. In our study, we analyze how OA affects the ability of ASC-derived from Hoffa's fat pad to differentiate into chondrocytes. Material and methodology We took knee Hoffa's pad samples and adipose tissue from the proximal thigh from 6 patients diagnosed with severe OA and from another 6 patients with an anterior cruciate ligament (ACL) rupture without OA. From all the patients, we took subcutaneous adipose tissue from the thigh, as the control group. Samples of synovial fluid (SF) were also extracted. The gene expression was analyzed by real-time quantitative polymerase chain reaction. Results PTH1R and MMP13 expression during chondrogenic differentiation were similar between OA and ACL groups, while the expression of OPG, FGF2, TGFβ, MMP3 were significantly lower in the OA group. Exposure of differentiated ASC to OA SF induced an increase in the expression of OPG, PTH1R, and MMP13 and a decrease in the expression of FGF2 in cell culture of the ACL group. However, expression of none of these factors was altered by the OA synovial fluid in ASC cells of the OA group. Conclusion OA of the knee also affects the mesenchymal stem cells of Hoffa fat, suggesting that Hoffa fat is a new actor in the OA degenerative process that can contribute to the origin, onset, and progression of the disease.

  5. Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.

    Science.gov (United States)

    Martin, Gregory G; Landrock, Danilo; Chung, Sarah; Dangott, Lawrence J; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

    2017-01-01

    The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice. © 2016 International Society for Neurochemistry.

  6. Copy Number Alterations in Enzyme-Coding and Cancer-Causing Genes Reprogram Tumor Metabolism.

    Science.gov (United States)

    Sharma, Ashwini Kumar; Eils, Roland; König, Rainer

    2016-07-15

    Somatic copy number alterations frequently occur in the cancer genome affecting not only oncogenic or tumor suppressive genes, but also passenger and potential codriver genes. An intrinsic feature resulting from such genomic perturbations is the deregulation in the metabolism of tumor cells. In this study, we have shown that metabolic and cancer-causing genes are unexpectedly often proximally positioned in the chromosome and share loci with coaltered copy numbers across multiple cancers (19 cancer types from The Cancer Genome Atlas). We have developed an analysis pipeline, Identification of Metabolic Cancer Genes (iMetCG), to infer the functional impact on metabolic remodeling from such coamplifications and codeletions and delineate genes driving cancer metabolism from those that are neutral. Using our identified metabolic genes, we were able to classify tumors based on their tissue and developmental origins. These metabolic genes were similar to known cancer genes in terms of their network connectivity, isoform frequency, and evolutionary features. We further validated these identified metabolic genes by (i) using gene essentiality data from several tumor cell lines, (ii) showing that these identified metabolic genes are strong indicators for patient survival, and (iii) observing a significant overlap between our identified metabolic genes and known cancer-metabolic genes. Our analyses revealed a hitherto unknown generic mechanism for large-scale metabolic reprogramming in cancer cells based on linear gene proximities between cancer-causing and -metabolic genes. We have identified 119 new metabolic cancer genes likely to be involved in rewiring cancer cell metabolism. Cancer Res; 76(14); 4058-67. ©2016 AACR. ©2016 American Association for Cancer Research.

  7. Effects of non-exercise activity and daily exercise activity upon glucose and fat metabolism in type 2 diabetes.

    Science.gov (United States)

    Miyamoto, Toshiaki; Fukuda, Kazuhito; Oshima, Yoshitake; Moritani, Toshio

    2016-10-01

    The purpose of this study was to disclose the relationship between objectively measured non-exercise activity (NEA) and moderate to vigorous physical activity (MVPA) using triaxial accelerometer and the effect of each activity on glucose and fat metabolism in active type 2 diabetes. Elucidating this relationship and effect would lead to support educational programs for the management of type 2 diabetes. Seventy-seven patients with type 2 diabetes who had performed daily programmed walking exercise participated in this cross-sectional study. Physical activity including NEA and MVPA was measured by triaxial accelerometer for 10 consecutive days and the measurements of body composition and glucose and lipid profile were performed. There was no significant correlation between NEA and MVPA in active type 2 diabetes. NEA had a significant inverse correlation with body fat (Pdiabetes.

  8. [Effect of estradiol on food intake, glucose and fat metabolism in mice C57BL/6J with mutation yellow at the agouti locus].

    Science.gov (United States)

    Iakovleva, T V; Makarova, E N; Kazantseva, A Iu; Bazhan, N M

    2012-05-01

    Mutation yellow at the agouti locus in mice (A(y)/a-mice) causes the increase of food intake and development of obesity and type 2 diabetes. In A(y)/a-females the disturbances of glucose and fat metabolisms occur after puberty. We have assumed that the mutation yellow violates the regulatory effect of estradiol on glucose and fat metabolism in mice. We investigated the effects of ovariectomy and estradiol treatment on body weight, food intake, glucose tolerance, plasma levels of glucose, insulin and etherified fatty acids in A(y)/a-females. C57Bl/6J females, not carrying yellow mutation at the agouti locus (a/a-mice), were used as a control. The data suggest that the yellow mutation did not affect estradiol regulation of food intake and glucose blood levels after a night of fasting, but, apparently, prevented estradiol participation in the regulation of glucose and fat metabolisms in the muscle and fat tissues.

  9. Change in Proportional Protein Intake in a 10-Week Energy-Restricted Low- or High-Fat Diet, in Relation to Changes in Body Size and Metabolic Factors

    Directory of Open Access Journals (Sweden)

    Tanja Stocks

    2013-05-01

    Full Text Available Objective: To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%, in relation to changes in body size and metabolic factors. Methods: Obese adults (n = 771 were randomised to a 600 kcal energy-deficient low-fat (20-25 fat% or high-fat (40-45 fat% diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (2 on outcomes. Results: The low-fat group with >2 prot% increase lost 1.1 kg more weight (p = 0.03 and reduced cholesterol by 0.25 mmol/l more (p = 0.003 than the high-fat group with >2 prot% decrease. These differences were 2.5-fold and 1.8-fold greater than the differences between the low-fat and high-fat groups while not considering prot% change. The high-fat group reduced plasma triglycerides more than the low-fat group, but not compared to those in the low-fat group with >2 units prot% increase (p fat-protein interaction = 0.01. Conclusions: Under energy restriction, participants on a low-fat diet who had increased the percentage energy intake from protein showed the greatest reduction in weight and cholesterol, and a triglyceride reduction equally large to that of participants on a high-fat diet.

  10. Artemisia iwayomogi Extract Attenuates High-Fat Diet-Induced Obesity by Decreasing the Expression of Genes Associated with Adipogenesis in Mice

    Directory of Open Access Journals (Sweden)

    Yeji Choi

    2013-01-01

    Full Text Available The objective of the present study was to determine whether Artemisia iwayomogi (AI extract reduces visceral fat accumulation and obesity-related biomarkers in mice fed a high-fat diet (HFD, and if so, whether these effects are exerted by modulation of the expression of genes associated with adipogenesis and inflammation. AI extract supplementation for 11 weeks significantly prevented HFD-induced increments in body weight, visceral adiposity, adipocyte hypertrophy, and plasma levels of lipids and leptin. Additionally, AI extract supplementation resulted in downregulation of adipogenic transcription factors (PPARγ2 and C/EBPα and their target genes (CD36, aP2, and FAS in epididymal adipose tissue compared to the HFD alone. The AI extract effectively reversed the HFD-induced elevations in plasma glucose and insulin levels and the homeostasis model assessment of insulin resistance index. Furthermore, the extract significantly decreased gene expression of proinflammatory cytokines (TNFα, MCP1, IL-6, IFNα, and INFβ in epididymal adipose tissue and reduced plasma levels of TNFα and MCP1 as compared to HFD alone. In conclusion, these results suggest that AI extract may prevent HFD-induced obesity and metabolic disorders, probably by downregulating the expression of genes related to adipogenesis and inflammation in visceral adipose tissue.

  11. Fat metabolism during exercise in patients with McArdle disease

    DEFF Research Database (Denmark)

    Ørngreen, M C; Jeppesen, T D; Andersen, S Tvede

    2009-01-01

    indicate that patients with McArdle disease have exaggerated fat oxidation during prolonged, low-intensity exercise and that increased fat oxidation may be an important mechanism of the spontaneous second wind. The fact that increasing availability of free fatty acids with more prolonged exercise did...... oxidation during exercise. METHODS: We studied total fat oxidation by indirect calorimetry and palmitate turnover by stable isotope methodology in 11 patients with McArdle disease and 11 healthy controls. Cycle exercise at a constant workload of 50% to 60% of maximal oxygen uptake capacity was used...... to evaluate fatty acid oxidation (FAO) in the patients. Healthy controls were exercised at the same absolute workload. RESULTS: We found that palmitate oxidation and disposal, total fat oxidation, and plasma levels of palmitate and total free fatty acids (FFAs) were significantly higher, whereas total...

  12. Deleted in breast cancer 1 limits adipose tissue fat accumulation and plays a key role in the development of metabolic syndrome phenotype.

    Science.gov (United States)

    Escande, Carlos; Nin, Veronica; Pirtskhalava, Tamar; Chini, Claudia C S; Tchkonia, Tamar; Kirkland, James L; Chini, Eduardo N

    2015-01-01

    Obesity is often regarded as the primary cause of metabolic syndrome. However, many lines of evidence suggest that obesity may develop as a protective mechanism against tissue damage during caloric surplus and that it is only when the maximum fat accumulation capacity is reached and fatty acid spillover occurs into to peripheral tissues that metabolic diseases develop. In this regard, identifying the molecular mechanisms that modulate adipocyte fat accumulation and fatty acid spillover is imperative. Here we identify the deleted in breast cancer 1 (DBC1) protein as a key regulator of fat storage capacity of adipocytes. We found that knockout (KO) of DBC1 facilitated fat cell differentiation and lipid accumulation and increased fat storage capacity of adipocytes in vitro and in vivo. This effect resulted in a "healthy obesity" phenotype. DBC1 KO mice fed a high-fat diet, although obese, remained insulin sensitive, had lower free fatty acid in plasma, were protected against atherosclerosis and liver steatosis, and lived longer. We propose that DBC1 is part of the molecular machinery that regulates fat storage capacity in adipocytes and participates in the "turn-off" switch that limits adipocyte fat accumulation and leads to fat spillover into peripheral tissues, leading to the deleterious effects of caloric surplus. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Correlation of Visceral Fat Area with Metabolic Risk Factors in Romanian Patients: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Hâncu Anca

    2015-12-01

    Full Text Available Background and Aims: The aim of the present study was to investigate the relationship between visceral fat area (VFA, estimated by bioimpedance, and cardiovascular risk factors independent of BMI and waist circumference in a cohort of Romanian patients. Material and Methods: This was a cross-sectional study, in which were collected data from 751 patients ≥18 years of age from Cluj-Napoca. Anthropometric, biochemistry, body composition and medical history parameters were recorded from patients’ files. Results: Compared with the participants with VFA <100 cm2, those with VFA ≥100 cm2 had significantly worse levels of the laboratory parameters describing the glycemic metabolism, lipid metabolism and liver functions (p <0.05 for all. A higher percentage of participants with VFA ≥100 cm2 had diabetes, obesity, hypertension, hypertriglyceridemia and hypo-HDL cholesterolemia (p <0.05 for all. VFA was correlated with systolic and diastolic blood pressure, total and LDL-cholesterol levels, triglycerides, ALT, previous diagnosis of diabetes, hypertriglyceridemia and hypo-HDL cholesterolemia independent of BMI and waist circumference. Conclusions: Among this cohort of Romanian adults, an increasing level of visceral adiposity was correlated with worse lipid and glucose metabolism parameters as well as with increased levels of ALT, which probably reflects liver fat deposition.

  14. Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

    Directory of Open Access Journals (Sweden)

    Zhai Hua-Ling

    2012-01-01

    Full Text Available Abstract Background There is a high prevalence of diabetes mellitus (DM and dyslipidemia in women with polycystic ovary syndrome (PCOS. The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. Methods Female Sprague-Dawley rats were divided into 3 groups: the control group(C, n = 10; the andronate-treated group (Andronate, n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks; and the andronate-treated and high-fat diet group (Andronate+HFD, n = 10. The rate of glucose appearance (Ra of glucose, gluconeogenesis (GNG, and the rate of glycerol appearance (Ra of glycerol were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. Results Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P P Conclusions Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.

  15. GRMD cardiac and skeletal muscle metabolism gene profiles are distinct.

    Science.gov (United States)

    Markham, Larry W; Brinkmeyer-Langford, Candice L; Soslow, Jonathan H; Gupte, Manisha; Sawyer, Douglas B; Kornegay, Joe N; Galindo, Cristi L

    2017-04-08

    Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, which codes for the dystrophin protein. While progress has been made in defining the molecular basis and pathogenesis of DMD, major gaps remain in understanding mechanisms that contribute to the marked delay in cardiac compared to skeletal muscle dysfunction. To address this question, we analyzed cardiac and skeletal muscle tissue microarrays from golden retriever muscular dystrophy (GRMD) dogs, a genetically and clinically homologous model for DMD. A total of 15 dogs, 3 each GRMD and controls at 6 and 12 months plus 3 older (47-93 months) GRMD dogs, were assessed. GRMD dogs exhibited tissue- and age-specific transcriptional profiles and enriched functions in skeletal but not cardiac muscle, consistent with a "metabolic crisis" seen with DMD microarray studies. Most notably, dozens of energy production-associated molecules, including all of the TCA cycle enzymes and multiple electron transport components, were down regulated. Glycolytic and glycolysis shunt pathway-associated enzymes, such as those of the anabolic pentose phosphate pathway, were also altered, in keeping with gene expression in other forms of muscle atrophy. On the other hand, GRMD cardiac muscle genes were enriched in nucleotide metabolism and pathways that are critical for neuromuscular junction maintenance, synaptic function and conduction. These findings suggest differential metabolic dysfunction may contribute to distinct pathological phenotypes in skeletal and cardiac muscle.

  16. Efficacy of azelaic acid on hepatic key enzymes of carbohydrate metabolism in high fat diet induced type 2 diabetic mice.

    Science.gov (United States)

    Muthulakshmi, Shanmugam; Saravanan, Ramalingam

    2013-06-01

    Azelaic acid (AzA), a C9 linear α,ω-dicarboxylic acid, is found in whole grains namely wheat, rye, barley, oat seeds and sorghum. The study was performed to investigate whether AzA exerts beneficial effect on hepatic key enzymes of carbohydrate metabolism in high fat diet (HFD) induced type 2 diabetic C57BL/6J mice. C57BL/6J mice were fed high fat diet for 10 weeks and subjected to intragastric administration of various doses (20 mg, 40 mg and 80 mg/kg BW) of AzA daily for the subsequent 5 weeks. Rosiglitazone (RSG) was used as reference drug. Body weight, food intake, plasma glucose, plasma insulin, blood haemoglobin (Hb), blood glycosylated haemoglobin (HbA1c), liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase), gluconeogenic enzymes(glucose-6-phosphatase and fructose-1,6-bisphosphatase), liver glycogen, plasma and liver triglycerides were examined in mice fed with normal standard diet (NC), high fat diet (HFD), HFD with AzA (HFD + AzA) and HFD with rosiglitazone (HFD + RSG). Among the three doses, 80 mg/kg BW of AzA was able to positively regulate plasma glucose, insulin, blood HbA1c and haemoglobin levels by significantly increasing the activity of hexokinase and glucose-6-phosphate dehydrogenase and significantly decreasing the activity of glucose-6-phosphatase and fructose-1,6-bisphosphatase thereby increasing the glycogen content in the liver. From this study, we put forward that AzA could significantly restore the levels of plasma glucose, insulin, HbA1c, Hb, liver glycogen and carbohydrate metabolic key enzymes to near normal in diabetic mice and hence, AzA may be useful as a biomaterial in the development of therapeutic agents against high fat diet induced T2DM. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. A Difference in Fatty Acid Composition of Isocaloric High-Fat Diets Alters Metabolic Flexibility in Male C57BL/6JOlaHsd Mice

    Czech Academy of Sciences Publication Activity Database

    Duivenvoorde, L. P. M.; van Schothorst, E. M.; Swarts, H. M.; Kuda, Ondřej; Steenbergh, E.; Termeulen, S.; Kopecký, Jan; Keijer, J.

    2015-01-01

    Roč. 10, č. 6 (2015), e0128515 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) 7E10059 Institutional support: RVO:67985823 Keywords : PUFA * satureted fatty acids * high fat diet * metabolic flexibility * indirect calorimetry Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.057, year: 2015

  18. Fat and carbohydrate metabolism during exercise in phosphoglucomutase type 1 deficiency

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Laforêt, Pascal; Echaniz-Laguna, Andoni

    2013-01-01

    Phosphoglucomutase type 1 (PGM1) deficiency is a rare metabolic myopathy in which symptoms are provoked by exercise.......Phosphoglucomutase type 1 (PGM1) deficiency is a rare metabolic myopathy in which symptoms are provoked by exercise....

  19. [Effect of different post-weaning dietary compositions on body fat content and hormone-sensitive lipase gene expression in rats fed with high-fat diet].

    Science.gov (United States)

    Zhang, Xiao-Hong; Wang, Xiao-Chun; Zhao, Li-Jun; Sun, Chang-Hao

    2006-09-01

    To study the effects of different postweaning dietary compositions on body fat content and hormone-sensitive lipase (HSL) gene expression in rats fed a high-fat diet. Male Wistar rats weaned on 24 days were randomly divided into A, B, C, D groups and were fed on high carbohydrate, high protein, high unsaturated fatty acid and high saturated fatty acid diet respectively. After 3 weeks, all rats were assigned to basic diet for two weeks, then rats from A group were randomly divided into A1 and A2 subgroups. A1 subgroup was fed on basic diet continuously. A2 subgroup and B, C and D groups were assigned to high-fat diet for six weeks. Eight rats from each group were sacrificed at the end of different treatments to detect body weight, body fat content and blood glucose level. RT-PCR was used to determine the gene expression of hormone-sensitive lipase in white adipose tissue. Body weight, body fat content and blood glucose level in C group were significantly lower than those in A2 subgroup on 11 weeks (P subgroup (P blood glucose level was higher than A2 subgroup on 11 weeks (P > 0.05). The body weight in D group was significantly lower than that in A2 subgroup (P blood glucose level were not significantly lower than A2 subgroup on 11 weeks (P > 0.05). The expression of HSL in B2 and C group was higher on 9 weeks and 11 weeks respectively. The HSL mRNA levels in all groups on 3 weeks were similar to that on 11 weeks. Feeding on high unsaturated-fatty acid diet after weaning may significantly reduce the body weight, body fat content, improve the abnormal blood glucose level in rats induced by high-fat diet. It was suggested that the high unsaturated-fatty acid diet can be reasonable for weaned rats and gene expression regulation may be involved in programming later obesity by early nutrition.

  20. Systemic adaptation of lipid metabolism in response to low- and high-fat diet in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    He, An-Yuan; Ning, Li-Jun; Chen, Li-Qiao; Chen, Ya-Li; Xing, Qi; Li, Jia-Min; Qiao, Fang; Li, Dong-Liang; Zhang, Mei-Ling; Du, Zhen-Yu

    2015-08-01

    Natural selection endows animals with the abilities to store lipid when food is abundant and to synthesize lipid when it is limited. However, the relevant adaptive strategy of lipid metabolism has not been clearly elucidated in fish. This study examined the systemic metabolic strategies of Nile tilapia to maintain lipid homeostasis when fed with low- or high-fat diets. Three diets with different lipid contents (1%, 7%, and 13%) were formulated and fed to tilapias for 10 weeks. At the end of the feeding trial, the growth rate, hepatic somatic index, and the triglyceride (TG) contents of serum, liver, muscle, and adipose tissue were comparable among three groups, whereas the total body lipid contents and the mass of adipose tissue increased with the increased dietary lipid levels. Overall quantitative PCR, western blotting and transcriptomic assays indicated that the liver was the primary responding organ to low-fat (LF) diet feeding, and the elevated glycolysis and accelerated biosynthesis of fatty acids (FA) in the liver is likely to be the main strategies of tilapia toward LF intake. In contrast, excess ingested lipid was preferentially stored in adipose tissue through increasing the capability of FA uptake and TG synthesis. Increasing numbers, but not enlarging size, of adipocytes may be the main strategy of Nile tilapia responding to continuous high-fat (HF) diet feeding. This is the first study illuminating the systemic adaptation of lipid metabolism responding to LF or HF diet in fish, and our results shed new light on fish physiology. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  1. Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism

    DEFF Research Database (Denmark)

    Alfieri, A; Martone, D; Randers, Morten Bredsgaard

    2015-01-01

    We investigated whether long-term recreational football training affects the expression of health-related biochemical and molecular markers in healthy untrained subjects. Five untrained healthy men trained for 1 h 2.4 times/week for 12 weeks and 1.3 times/week for another 52 weeks. Blood samples...... are directly or indirectly involved in the glucose and lipid oxidative metabolism. Multiple linear regression analysis revealed that fat percentage was independently associated with NAMPT, PPARγ and adiponectin expression. In conclusion, long-term recreational football training could be a useful tool...... and a muscle biopsy from the vastus lateralis were collected at T0 (pre intervention) and at T1 (post intervention). Gene expression was measured by RTqPCR on RNA extracted from muscle biopsies. The expression levels of the genes principally involved in energy metabolism (PPARγ, adiponectin, AMPKα1/α2, TFAM...

  2. Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD.

    Science.gov (United States)

    Luo, Yuwen; Burrington, Christine M; Graff, Emily C; Zhang, Jian; Judd, Robert L; Suksaranjit, Promporn; Kaewpoowat, Quanhathai; Davenport, Samantha K; O'Neill, Ann Marie; Greene, Michael W

    2016-03-15

    nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD+F/S-fed mice. HFWD+F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGFβ gene expression. Furthermore, HWFD+F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD+F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression. Copyright © 2016 the American Physiological Society.

  3. The WWOX Gene Modulates HDL and Lipid Metabolism

    Science.gov (United States)

    Iatan, Iulia; Choi, Hong Y.; Ruel, Isabelle; Linga Reddy, M.V. Prasad; Kil, Hyunsuk; Lee, Jaeho; Abu Odeh, Mohammad; Salah, Zaidoun; Abu-Remaileh, Muhannad; Weissglas-Volkov, Daphna; Nikkola, Elina; Civelek, Mete; Awan, Zuhier; Croce, Carlo M.; Aqeilan, Rami I.; Pajukanta, Päivi; Aldaz, C. Marcelo; Genest, Jacques

    2014-01-01

    Background Low high-density lipoprotein-cholesterol (HDL-C) constitutes a major risk factor for atherosclerosis. Recent studies from our group reported a genetic association between the WW domain-containing oxidoreductase (WWOX) gene and HDL-C levels. Here, through next-generation resequencing, in vivo functional studies and gene microarray analyses, we investigated the role of WWOX in HDL and lipid metabolism. Methods and Results Using next-generation resequencing of the WWOX region, we first identified 8 variants significantly associated and perfectly segregating with the low-HDL trait in two multi-generational French Canadian dyslipidemic families. To understand in vivo functions of WWOX, we used liver-specific Wwoxhep−/− and total Wwox−/− mice models, where we found decreased ApoA-I and ABCA1 levels in hepatic tissues. Analyses of lipoprotein profiles in Wwox−/−, but not Wwox hep−/− littermates, also showed marked reductions in serum HDL-C concentrations, concordant with the low-HDL findings observed in families. We next obtained evidence of a gender-specific effect in female Wwoxhep−/− mice, where an increase in plasma triglycerides and altered lipid metabolic pathways by microarray analyses were observed. We further identified a significant reduction in ApoA-I and LPL, and upregulation in Fas, Angptl4 and Lipg, suggesting that the effects of Wwox involve multiple pathways, including cholesterol homeostasis, ApoA-I/ABCA1 pathway, and fatty acid biosynthesis/triglyceride metabolism. Conclusions Our data indicate that WWOX disruption alters HDL and lipoprotein metabolism through several mechanisms and may account for the low-HDL phenotype observed in families expressing the WWOX variants. These findings thus describe a novel gene involved in cellular lipid homeostasis, which effects may impact atherosclerotic disease development. PMID:24871327

  4. Rs9939609 Variant of the Fat Mass and Obesity-Associated Gene and Trunk Obesity in Adolescents

    Science.gov (United States)

    Mangge, Harald; Renner, Wilfried; Almer, Gunter; Weghuber, Daniel; Möller, Reinhard; Horejsi, Renate

    2011-01-01

    A common T/A polymorphism (rs9939609) in the fat mass and obesity associated (FTO) gene was found associated with early-onset and severe obesity in both adults and children. However, recent observations failed to find associations of FTO with obesity. To investigate the genetic background of early obesity, we analysed the single nucleotide polymorphism (SNP) rs9939609 of FTO in 371 styrian adolescents towards degree of obesity, subcutaneous adipose tissue (SAT)-distribution determined by lipometry, early metabolic and preatherosclerotic symptoms. The percentage of AA homozygotes for the rs9939609 SNP of FTO was significantly increased in the obese adolescents. Compared to the TT wildtype, AA homozygotes showed significantly elevated values of SAT thickness at the trunk-located lipometer measure points neck and frontal chest, body weight, body mass index, waist, and hip circumference. No associations were found with carotis communis intima media thickness, systolic, diastolic blood pressure, ultrasensitive C-reactive protein (US-CRP), homocystein, total cholesterol, triglycerides, HDL cholesterol, oxidized LDL, fasted glucose, insulin, HOMA-index, liver transaminases, uric acid, and adipokines like resistin, leptin, and adiponectin. Taken together, to the best of our knowledge we are the first to report that the rs9939609 FTO SNP is associated with trunk weighted obesity as early as in adolescence. PMID:21318054

  5. Rs9939609 Variant of the Fat Mass and Obesity-Associated Gene and Trunk Obesity in Adolescents

    Directory of Open Access Journals (Sweden)

    Harald Mangge

    2011-01-01

    Full Text Available A common T/A polymorphism (rs9939609 in the fat mass and obesity associated (FTO gene was found associated with early-onset and severe obesity in both adults and children. However, recent observations failed to find associations of FTO with obesity. To investigate the genetic background of early obesity, we analysed the single nucleotide polymorphism (SNP rs9939609 of FTO in 371 styrian adolescents towards degree of obesity, subcutaneous adipose tissue (SAT-distribution determined by lipometry, early metabolic and preatherosclerotic symptoms. The percentage of AA homozygotes for the rs9939609 SNP of FTO was significantly increased in the obese adolescents. Compared to the TT wildtype, AA homozygotes showed significantly elevated values of SAT thickness at the trunk-located lipometer measure points neck and frontal chest, body weight, body mass index, waist, and hip circumference. No associations were found with carotis communis intima media thickness, systolic, diastolic blood pressure, ultrasensitive C-reactive protein (US-CRP, homocystein, total cholesterol, triglycerides, HDL cholesterol, oxidized LDL, fasted glucose, insulin, HOMA-index, liver transaminases, uric acid, and adipokines like resistin, leptin, and adiponectin. Taken together, to the best of our knowledge we are the first to report that the rs9939609 FTO SNP is associated with trunk weighted obesity as early as in adolescence.

  6. A variant in the fat mass and obesity-associated gene (FTO) and variants near the melanocortin-4 receptor gene (MC4R) do not influence dietary intake

    DEFF Research Database (Denmark)

    Hasselbalch, Ann L; Angquist, Lars; Christiansen, Lene

    2010-01-01

    We investigated the role of the fat mass and obesity associated gene (FTO) and variants near the melanocortin-4 receptor gene (MC4R) in modulating habitual intake of total energy and macronutrients, glycemic index, glycemic load, dietary energy density, and energy from 20 food groups in adults...

  7. Carbenoxolone treatment ameliorated metabolic syndrome in WNIN/Ob obese rats, but induced severe fat loss and glucose intolerance in lean rats.

    Directory of Open Access Journals (Sweden)

    Siva Sankara Vara Prasad Sakamuri

    Full Text Available BACKGROUND: 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1 regulates local glucocorticoid action in tissues by catalysing conversion of inactive glucocorticoids to active glucocorticoids. 11β-HSD1 inhibition ameliorates obesity and associated co-morbidities. Here, we tested the effect of 11β-HSD inhibitor, carbenoxolone (CBX on obesity and associated comorbidities in obese rats of WNIN/Ob strain, a new animal model for genetic obesity. METHODOLOGY/PRINCIPAL FINDINGS: Subcutaneous injection of CBX (50 mg/kg body weight or volume-matched vehicle was given once daily for four weeks to three month-old WNIN/Ob lean and obese rats (n = 6 for each phenotype and for each treatment. Body composition, plasma lipids and hormones were assayed. Hepatic steatosis, adipose tissue morphology, inflammation and fibrosis were also studied. Insulin resistance and glucose intolerance were determined along with tissue glycogen content. Gene expressions were determined in liver and adipose tissue. CBX significantly inhibited 11β-HSD1 activity in liver and adipose tissue of WNIN/Ob lean and obese rats. CBX significantly decreased body fat percentage, hypertriglyceridemia, hypercholesterolemia, insulin resistance in obese rats. CBX ameliorated hepatic steatosis, adipocyte hypertrophy, adipose tissue inflammation and fibrosis in obese rats. Tissue glycogen content was significantly decreased by CBX in liver and adipose tissue of obese rats. Severe fat loss and glucose- intolerance were observed in lean rats after CBX treatment. CONCLUSIONS/SIGNIFICANCE: We conclude that 11β-HSD1 inhibition by CBX decreases obesity and associated co-morbidities in WNIN/Ob obese rats. Our study supports the hypothesis that inhibition of 11β-HSD1 is a key strategy to treat metabolic syndrome. Severe fat loss and glucose -intolerance by CBX treatment in lean rats suggest that chronic 11β-HSD1 inhibition may lead to insulin resistance in normal conditions.

  8. Effects of α-Galactooligosaccharides from Chickpeas on High-Fat-Diet-Induced Metabolic Syndrome in Mice.

    Science.gov (United States)

    Dai, Zhuqing; Lyu, Wanyong; Xie, Minhao; Yuan, Qingxia; Ye, Hong; Hu, Bing; Zhou, Li; Zeng, Xiaoxiong

    2017-04-19

    The gut microbiota has the ability to modulate host energy homeostasis, which may regulate metabolic disorders. Functional oligosaccharide may positively regulate the intestinal microbiota. Therefore, effects of α-galactooligosaccharides (α-GOS) from chickpea on high-fat-diet (HFD)-induced metabolic syndrome and gut bacterial dysbiosis were investigated. After 6 weeks of intervention, HFD led to significant increases in levels of blood glucose, total cholesterol, triglyceride, glycated serum protein, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol of mice compared to normal-chow-fed mice. Meanwhile, all of the α-GOS-treated groups significantly decreased above parameters compared to the HFD group. HFD could significantly decrease the content of all bacteria, especially Bacteroides (9.82 ± 0.09 versus 10.3 ± 0.10; p bacterial ecosystem in a positive way.

  9. Noise propagation in synthetic gene circuits for metabolic control.

    Science.gov (United States)

    Oyarzún, Diego A; Lugagne, Jean-Baptiste; Stan, Guy-Bart V

    2015-02-20

    Dynamic control of enzyme expression can be an effective strategy to engineer robust metabolic pathways. It allows a synthetic pathway to self-regulate in response to changes in bioreactor conditions or the metabolic state of the host. The implementation of this regulatory strategy requires gene circuits that couple metabolic signals with the genetic machinery, which is known to be noisy and one of the main sources of cell-to-cell variability. One of the unexplored design aspects of these circuits is the propagation of biochemical noise between enzyme expression and pathway activity. In this article, we quantify the impact of a synthetic feedback circuit on the noise in a metabolic product in order to propose design criteria to reduce cell-to-cell variability. We consider a stochastic model of a catalytic reaction under negative feedback from the product to enzyme expression. On the basis of stochastic simulations and analysis, we show that, depending on the repression strength and promoter strength, transcriptional repression of enzyme expression can amplify or attenuate the noise in the number of product molecules. We obtain analytic estimates for the metabolic noise as a function of the model parameters and show that noise amplification/attenuation is a structural property of the model. We derive an analytic condition on the parameters that lead to attenuation of metabolic noise, suggesting that a higher promoter sensitivity enlarges the parameter design space. In the theoretical case of a switch-like promoter, our analysis reveals that the ability of the circuit to attenuate noise is subject to a trade-off between the repression strength and promoter strength.

  10. Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice.

    Science.gov (United States)

    Gotthardt, Juliet D; Verpeut, Jessica L; Yeomans, Bryn L; Yang, Jennifer A; Yasrebi, Ali; Roepke, Troy A; Bello, Nicholas T

    2016-02-01

    Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%-52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%-13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%-42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%-60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%-32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%-75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy.

  11. Quantitative protein and fat metabolism in bull calves treated with beta-adrenergic agonist

    DEFF Research Database (Denmark)

    Chwalibog, André; Jensen, K; Thorbek, G

    1996-01-01

    Protein and energy utilization and quantitative retention of protein, fat and energy was investigated with 12 Red Danish bulls during two subsequent 6 weeks trials (Sections A and B) at a mean live weight of 195 and 335 kg respectively. Treatments were control (Group 1) and beta-agonist (L-644...... was strongly influenced by treatment, with the highest values for Group 2 in both sections. The protein retention increased with 25% in Group 2, with the highest increment of 113 g/d in Section B. The fat retention decreased in treated animals, most pronounced in Group 3, where the reduction was about 50......% with a mean decrease of 145 g/d in Section B. The total energy retention was not different between control animals and Group 2 in both sections, but there was a shift in energy retention from fat to protein. The higher levels of beta-agonist used in Group 3 generated the same increase in protein retention...

  12. Effects of ethinyl estradiol-cyproterone acetate treatment on metabolic syndrome, fat distribution and carotid intima media thickness in polycystic ovary syndrome.

    Science.gov (United States)

    Karabulut, Aysun; Demirlenk, Semra; Sevket, Osman

    2012-04-01

    To evaluate the effects of ethinyl estradiol-cyproterone acetate (EE-CA) treatment on metabolic and cardiovascular risk factors, and body fat distribution in polycystic ovary syndrome (PCOS) after 6-month treatment. Thirty women with PCOS were evaluated before and after 6 months of EE-CA treatment. Anthropometrical measurements, hormonal levels, lipid and glucose profile were evaluated. Body fat thickness in four regions and carotid intima media thickness (IMT) were measured. Interval change in antropometric measurements, glucose and lipid profile, carotid IMT and body fat distribution was evaluated before and after 6-month EE-CA treatment. Ferriman-Gallwey score and serum testosterone levels were significantly decreased after EE-CA treatment (p fat thicknesses decreased, and mid-thigh fat thickness increased after treatment period. However, only the alteration in subcutaneous fat thickness achieved a statistical significance (p fat thickness after 6-month treatment, it has no beneficial effect with respect to visceral fat thickness, metabolic and cardiovascular risk factors.

  13. Regional variations in HDL metabolism in human fat cells: effect of cell size

    International Nuclear Information System (INIS)

    Despres, J.; Fong, B.S.; Julien, P.; Jimenez, J.; Angel, A.

    1987-01-01

    Abdominal obesity is related to reduced plasma high-density lipoprotein (HDL) cholesterol, and both are associated with cardiovascular disease risk. The authors have observed that plasma membranes from abdominal subcutaneous adipocytes have a greater HDL binding capacity than omental fat cell plasma membranes. The present study examined whether these binding characteristics could be due to differences in fat cell size or cholesterol concentration between the two adipose depots. Abdominal subcutaneous and deep omental fat were obtained from massively obese patients at surgery. Subcutaneous abdominal fat cells were significantly larger and their cellular cholesterol content greater than omental adipocytes. The uptake of HDL by collagenase-isolated fat cells was studied by incubating the cells for 2 h at 37 0 C with 10 μg/ml 125 I-HDL 2 or 125 I-HDL 3 . In both depots, the cellular uptake of 125 I-HDL 2 and 125 I-HDL 3 was specifically inhibited by addition of 25-fold excess unlabeled HDL and a close correlation was observed between the cellular uptake of 125 I-HDL 2 and 125 I-HDL 3 . In obese patients, the uptake of 125 I-HDL was higher in subcutaneous cells than in omental cells. The cellular 125 I-HDL uptake was significantly correlated with adipocyte size and fat cell cholesterol content but not with adipocyte cholesterol concentration. These results suggest that the higher HDL uptake observed in subcutaneous cells compared with omental cells in obesity is the result of differences in adipocyte size rather than differences in the cholesterol concentration (cholesterol-to-triglyceride ratio). The increased interaction of HDL with hypertrophied abdominal adipocytes may play an important role in determining the lipid composition of HDL in obesity

  14. Fat and carbohydrates in the diet: Its metabolic contribution to obesity in Chilean women

    International Nuclear Information System (INIS)

    Diaz, E.; Galgani, J.; Morales, I.; Salazar, G.; Uauy, R.

    2002-01-01

    The effects of changes in dietary fatty acid composition on macronutrient oxidation were studied on controls and 6 obese women, 30-45 years old. Anthropometry, body composition, physical activity, continuous indirect calorimetry (200 min), plasma fatty acids, serum insulin and glucose were measured. The study was performed using a crossover design: baseline and three-period 2wk each: canola oil supplementation, washout and sunflower oil supplementation. Subjects were provided with commercially available oil (1 L/wk) either canola or sunflower during the corresponding period. Oil treatment produced significant modifications of plasma fatty acid profile, according to the type of oil consumed. In both groups, most of the fat provided was oxidised (ratio oxidised/intake: 79-102%) in the two dietary regimes, no differences were found between groups. Controls however, had a higher fat oxidation (mg/kg fat-free mass) with sunflower compared to canola treatment. Changes in plasma polyunsaturated/saturated ratio (P/S) from canola to sunflower treatment were not associated to fat oxidation. Changes in plasma n6/n3 ratio from canola to sunflower treatment showed a positive association with fat oxidation in controls (r=0. 72) and a negative association in obese (r=-0.79). Carbohydrate oxidation was on average 20-29% of CHO intake. Glucose oxidation was not associated to n6/n3 ratio from canola to sunflower treatment, but it was inversely correlated to PIS ratio changes in both groups. With sunflower treatment obese showed a higher CHO oxidation (mg/kg fat-free mass) associated to a greater insulin response compared to controls. This study showed that the type of oil can induce differences in substrate oxidation. Canola oil intake could be stimulated based on its smaller insulin response in subjects predisposed to hyperinsulinemia and insulin resistance. (author)

  15. Fat and carbohydrates in the diet: Its metabolic contribution to obesity in Chilean women

    International Nuclear Information System (INIS)

    Diaz, E.O.; Salazar, G.; Uauy, R.

    1999-01-01

    It has been found that children and adults in the Chilean population are getting obese in a rapidly raising proportion. There is a cohort of children less than six years old, which are regularly controlled by the Ministry of Health. From this information and studies carried out at INTA, it is known that the prevalence is raising continuously. Unfortunately, this can not be ascertained in adults where the nutritional situation is assessed only in small groups, which are not representative of the general population. The problem with adults is that the healthy population does not attend to the medical clinics unless they are already ill. The studies conducted in Chilean adults have found that >40% of low socio-economic status (SES) women are suffering from obesity. A intriguing aspect in our situation is that although sedentarism is frequent in adult women (as a possible cause of positive energy balance), their intake is based on a high proportion of carbohydrates (CHO) but not much fat (50-70 g on average). It may be suggested that the excess CHO can be converted into fat through denovo lipogenesis but this process is less important as cause of obesity in humans. A more plausible cause of this problem is likely to be related to the diet. The oxidation hierarchy of macronutrients shows that whenever CHO and fat are available, the former will be firstly oxidised. This way, fat can be spared even when eaten in small amounts, accumulating in the mid-long term. Another important dietary aspect is provided by its fatty acids composition that according to animal studies, seems to modulate fat oxidation. In addition to these, glycemic effects of CHO eaten in combination with the same meal can further potentiate fat storage. This proposal aims to test the dietary effects mentioned above by using indirect calorimetry in tandem with stable isotopes methodologies in a group of normal weight and obese women. (author)

  16. The relationship between epicardial fat and indices of obesity and the metabolic syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Rabkin, Simon W

    2014-02-01

    Epicardial fat (epicardial adipose tissue, EAT) has been implicated in the pathogenesis of coronary artery disease (CAD). The objective of this study was to examine the relationship between EAT and generalized obesity, central or visceral adipose tissue (VAT), and the components of the metabolic syndrome--systolic blood pressure (SBP), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and fasting blood glucose (FBG)--that are linked to CAD. A systematic review of the literature, following meta-analysis guidelines, was conducted until May, 2013, using the search strategy "Obesity" OR "abdominal obesity" OR "metabolic syndrome" OR "metabolic syndrome X" AND "epicardial fat". Thirty-eight studies fulfilled the criteria. There was a highly significant (Pcorrelation between EAT and body mass index (BMI), waist circumference (WC), or VAT. The correlation between EAT and VAT was significantly (Pcorrelation between EAT and WC, which in turn was significantly greater than the correlation between EAT and BMI. Overall, EAT was 7.5 ± 0.1 mm in thickness in the metabolic syndrome (n=427) compared to 4.0 ± 0.1 mm in controls (n=301). EAT correlated significantly (PHDL, and FBG, but the strength of the association was less than one-half of the relationship of EAT to indices of obesity. The results of multivariate analysis were less consistent but show a relationship between EAT and metabolic syndrome independent of BMI. In summary, the very strong correlation between EAT and VAT suggests a relationship between these two adipose tissue depots. Measurement of EAT can be useful to indicate VAT. Whereas EAT correlates significantly with each of the components of the metabolic syndrome- SBP, TGs, HDL, or FBG-the magnitude of the relationship is considerably and significantly less than the relationship of EAT to BMI. These data show the strong relationship between EAT and BMI but especially with WC and VAT. They also demonstrate the smaller magnitude of the

  17. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

    Science.gov (United States)

    Li, Songtao; Liao, Xilu; Meng, Fanyu; Wang, Yemei; Sun, Zongxiang; Guo, Fuchuan; Li, Xiaoxia; Meng, Man; Li, Ying; Sun, Changhao

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

  18. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

    Directory of Open Access Journals (Sweden)

    Songtao Li

    Full Text Available BACKGROUND: Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA, an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD-induced obese non-alcoholic fatty liver disease (NAFLD rat model. METHODOLOGY/PRINCIPAL FINDINGS: Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

  19. Resistance Training Combined With Diet Decreases Body Fat While Preserving Lean Mass Independent of Resting Metabolic Rate: A Randomized Trial.

    Science.gov (United States)

    Miller, Todd; Mull, Stephanie; Aragon, Alan Albert; Krieger, James; Schoenfeld, Brad Jon

    2018-01-01

    The purpose of this study was to determine the effects of resistance training only (RT; n = 10), dietary intervention only (DIET; n = 10), resistance training plus diet (RT+DIET; n = 10), and control (CON; n = 10) on body composition and resting metabolic rate (RMR) in a cohort of 40 premenopausal female volunteers. Subjects in DIET and RT+DIET were provided with daily macronutrient and calorie goals based on DXA and RMR tests, with protein maintained at 3.1 g/kg/day. Subjects in the RT and RT+DIET groups performed a supervised progressive RT program consisting of exercises for all the major muscle groups of the body. Results showed a significant month-by-group interaction for change in fat mass with no significant linear trend for control. The three treatment groups all showed significant linear decreases in fat mass, but the slope of the decrease became progressively steeper from the RT, to DIET, to RT+DIET. A significant linear increase for lean mass was seen for resistance training only. There was a nonsignificant increase in RMR in all groups from Month 0 to Month 4 but no significant month by group interaction. In conclusion, significant reductions in fat mass were achieved by all experimental groups, but results were maximized by RT+DIET. Only the RT group showed significant increases in lean mass.

  20. Effects of High Fat Feeding and Diabetes on Regression of Atherosclerosis Induced by Low-Density Lipoprotein Receptor Gene Therapy in LDL Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Florian Willecke

    Full Text Available We tested whether a high fat diet (HFD containing the inflammatory dietary fatty acid palmitate or insulin deficient diabetes altered the remodeling of atherosclerotic plaques in LDL receptor knockout (Ldlr-/- mice. Cholesterol reduction was achieved by using a helper-dependent adenovirus (HDAd carrying the gene for the low-density lipoprotein receptor (Ldlr; HDAd-LDLR. After injection of the HDAd-LDLR, mice consuming either HFD, which led to insulin resistance but not hyperglycemia, or low fat diet (LFD, showed regression compared to baseline. However there was no difference between the two groups in terms of atherosclerotic lesion size, or CD68+ cell and lipid content. Because of the lack of effects of these two diets, we then tested whether viral-mediated cholesterol reduction would lead to defective regression in mice with greater hyperglycemia. In both normoglycemic and streptozotocin (STZ-treated hyperglycemic mice, HDAd-LDLR significantly reduced plasma cholesterol levels, decreased atherosclerotic lesion size, reduced macrophage area and lipid content, and increased collagen content of plaque in the aortic sinus. However, reductions in anti-inflammatory and ER stress-related genes were less pronounced in STZ-diabetic mice compared to non-diabetic mice. In conclusion, HDAd-mediated Ldlr gene therapy is an effective and simple method to induce atherosclerosis regression in Ldlr-/- mice in different metabolic states.

  1. The role of dipeptidyl peptidase 4 inhibitors in fat metabolism in patients with type 2 diabetes and obesity

    Directory of Open Access Journals (Sweden)

    Aleksander Sergeevich Ametov

    2015-07-01

    Full Text Available Objective. To evaluate the influence of combined therapy of sitagliptin and metformin on fat metabolism in patients with type 2 diabetes mellitus.Methods. The study included 82 patients (age, 55.3±9.1 years with obesity and lipid metabolism disorders. None of the patients had reached their target glycated haemoglobin levels after metformin and diet therapy. Patients in group 1 (n=42 received 1.5–2-g metformin daily before the study and were switched to a formulation of 100-mg sitagliptin and 2-g metformin once a day. Patients in group 2 (n=40 were on a diet therapy before inclusion and were started on 2-g metformin/day. The following were evaluated at baseline and after 6 months of therapy: fasting glucose levels, postprandial glucose levels, glycated haemoglobin, weight, body mass index, waist circumference and lipid profile; insulin, proinsulin, leptin and adiponectin levels; insulin resistance using the homeostatic model assessment (HOMA of β-cell function (HOMA-β and insulin resistance (HOMA-IR. In addition, magnetic resonance imaging was performed to assess the amount of visceral fat for the total cohort.Results. After 6 months, glycated haemoglobin decreased by 18.52% (p <0.001 in group 1 and by 8.17% (p <0.001 in group 2. Fasting plasma glucose and postprandial glucose levels in group 1 were reduced by 21% (p <0.001 and 26.35% (p <0.001, respectively; the corresponding reductions in group 2 were 1.45% (p >0.05 and 5.31% (p <0.05, respectively. HOMA-β increased by 33% in group 1 (p <0.001 and by 11% in group 2 (p >0.05. Adiponectin levels increased by 27.06% (p <0.001 in group 1 and by 7.16% in group 2 (p <0.001. Leptin levels were reduced by 30.47% (p <0.001 in group 1 and by 5.41% in group 2 (p <0.001. Magnetic resonance imaging showed a 7.52% reduction in visceral fat for group 1 (p <0.001 and a 1.76% reduction for group 2 (p <0.01. The comparison of subcutaneous fat dynamics did not show statistically significant differences

  2. Cocoa butter and safflower oil elicit different effects on hepatic gene expression and lipid metabolism in rats.

    Science.gov (United States)

    Gustavsson, Carolina; Parini, Paolo; Ostojic, Jovanca; Cheung, Louisa; Hu, Jin; Zadjali, Fahad; Tahir, Faheem; Brismar, Kerstin; Norstedt, Gunnar; Tollet-Egnell, Petra

    2009-11-01

    The aim of this study was to compare the effects of cocoa butter and safflower oil on hepatic transcript profiles, lipid metabolism and insulin sensitivity in healthy rats. Cocoa butter-based high-fat feeding for 3 days did not affect plasma total triglyceride (TG) levels or TG-rich VLDL particles or hepatic insulin sensitivity, but changes in hepatic gene expression were induced that might lead to increased lipid synthesis, lipotoxicity, inflammation and insulin resistance if maintained. Safflower oil increased hepatic beta-oxidation, was beneficial in terms of circulating TG-rich VLDL particles, but led to reduced hepatic insulin sensitivity. The effects of safflower oil on hepatic gene expression were partly overlapping with those exerted by cocoa butter, but fewer transcripts from anabolic pathways were altered. Increased hepatic cholesterol levels and increased expression of hepatic CYP7A1 and ABCG5 mRNA, important gene products in bile acid production and cholesterol excretion, were specific effects elicited by safflower oil only. Common effects on gene expression included increased levels of p8, DIG-1 IGFBP-1 and FGF21, and reduced levels of SCD-1 and SCD-2. This indicates that a lipid-induced program for hepatic lipid disposal and cell survival was induced by 3 days of high-fat feeding, independent on the lipid source. Based on the results, we speculate that hepatic TG infiltration leads to reduced expression of SCD-1, which might mediate either neutral, beneficial or unfavorable effects on hepatic metabolism upon high-fat feeding, depending on which fatty acids were provided by the diet.

  3. Identification of behavioural and metabolic factors predicting adiposity sensitivity to both high fat and high carbohydrate diets in rats.

    Directory of Open Access Journals (Sweden)

    Patrick Christian Even

    2011-12-01

    Full Text Available Individuals exhibit a great variation in their body weight gain response to a high-fat diet. Identification of predictive factors would enable better directed intervention towards susceptible individuals to treat obesity, and uncover potential mechanisms for treatment targeting. We set out to identify predictive behavioural and metabolic factors in an outbred rat model. 12 rats were analysed in metabolic cages for a period of 5 days during both high carbohydrate diet (HCD, and transition to a high fat diet (HFD. After a recovery period, rats were given a HFD for 6 days to identify those resistant or sensitive to it according to body weight gain. Rats were dissected at the end of the study to analyse body composition. This showed that in rats fed a HCD during most of their life, small differences in final body weight hid large variations in adiposity, allowing separation of rats into a second classification of carbohydrate-sensitive or -resistant. Meal size and meal number were found to be good predictors of sensitivity to a HFD, intensity of motor activity and ingestion speed good predictors of sensitivity to a HCD. Rats that were sensitive to the HCD could be resistant to the HFD and vice versa. This contributes to the idea that to be obesity prone does not necessarily need a HFD, it can also happen under a HCD, and be a hidden adiposity change with stable body weight.

  4. Dynamic regulation of genes involved in mitochondrial DNA replication and transcription during mouse brown fat cell differentiation and recruitment

    DEFF Research Database (Denmark)

    Murholm, Maria; Dixen, Karen; Qvortrup, Klaus

    2009-01-01

    ) and a remarkably higher mitochondrial abundance in brown adipocytes. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a comprehensive characterisation of gene expression linked to mitochondrial DNA replication, transcription and function during white and brown fat cell differentiation in vitro as well as in white...... and brown fat, brown adipose tissue fractions and in selected adipose tissues during cold exposure. We find a massive induction of the majority of such genes during brown adipocyte differentiation and recruitment, e.g. of the mitochondrial transcription factors A (Tfam) and B2 (Tfb2m), whereas only a subset...

  5. Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study.

    Science.gov (United States)

    Yuan, Fahu; Wang, Hualin; Tian, Yu; Li, Qi; He, Lei; Li, Na; Liu, Zhiguo

    2016-02-01

    Intake of fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) is believed to be beneficial against development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study was to gain further understanding of the potential mechanisms of the protective effects of fish oil against NAFLD. Ten male Sprague-Dawley rats were fed a control diet (CON), a Western style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively. The development of liver steatosis and fibrosis were verified by histological and biochemical examination. Hepatic transcriptome were extracted for RNA-seq analysis, and particular results were confirmed by real-time polymerase chain reaction (PCR). The consumption of fish oil significantly ameliorated WD-induced dyslipidemia, transaminase elevation, hepatic steatosis, inflammatory infiltration, and fibrosis. Hepatic RNA-Seq analysis showed that long-term intake of fish oil restored the expression of circadian clock-related genes per2 and per3, which were reduced in WD fed animals. Fish oil consumption also corrected the expression levels of genes involved in fatty acid and cholesterol metabolism, such as Srebf1, Fasn, Scd1, Insig2, Cd36, Cyp7a1, Abcg5, Abcg8 and Pcsk9. Moreover, the expression levels of pro-inflammation genes Mcp1, Socs2, Sema4a, and Cd44 in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation. The present study demonstrates fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation. Our findings add to the current understanding on the benefits of n-3 PUFAs against NAFLD.

  6. (Im) Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis

    NARCIS (Netherlands)

    He, F.; Fromion, V.; Westerhoff, H.V.

    2013-01-01

    Background: Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a

  7. Effects of coconut oil consumption on energy metabolism, cardiometabolic risk markers, and appetitive responses in women with excess body fat.

    Science.gov (United States)

    Valente, Flávia Xavier; Cândido, Flávia Galvão; Lopes, Lílian Lelis; Dias, Desirrê Morais; Carvalho, Samantha Dalbosco Lins; Pereira, Patrícia Feliciano; Bressan, Josefina

    2017-04-12

    Virgin coconut oil (VCO) is a medium-chain fatty acid source with popularly attributed benefits on obesity management. However, its role on obesity requires elucidation due to its saturated nature. In the study herein, we investigated acute effects of VCO consumption on energy metabolism, cardiometabolic risk markers, and appetitive responses in women with excess body fat. Fifteen adult women with excess body fat (37.43 ± 0.83%) participated in this randomized, crossover, controlled study. Two isocaloric mixed breakfasts containing 25 mL of VCO or control (extra-virgin olive oil-C) were evaluated. Resting energy expenditure (REE), fat oxidation rate (FOR), diet induced thermogenesis (DIT) and appetitive subjective responses were assessed at fasting and postprandial periods (up to 240 min). Cardiometabolic risk markers were assessed at fasting and up to 180 min postprandially. VCO did not affect REE, FOR, and DIT compared to C. In addition, VCO did not cause deleterious change in triglycerides, total cholesterol, HDL-c, LDL-c, triglycerides/HDL-c ratio, uric acid, glucose and Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR) (P time×treatment  > 0.05). However, VCO suppressed less hunger (P time×treatment  = 0.003), total satiety (P iAUC  = 0.021) and total fullness (P iAUC  = 0.035) responses than C. VCO consumption did not acutely change energy metabolism and cardiometabolic risk markers when added to a mixed breakfast but promoted less appetitive responses.

  8. Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice

    Directory of Open Access Journals (Sweden)

    L.B. Oliveros

    2004-03-01

    Full Text Available We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet, or the control diet containing soybean oil as fat source (10 mice per group. The fat content of each diet was 15% (w/w. Mice were fed for 6 weeks and then sacrificed. The concentration of total lipids, triglycerides, (LDL + VLDL-cholesterol, thiobarbituric acid-reactive substances (TBARS and reduced glutathione were increased in the plasma of mice fed the COCO diet, without changes in phospholipid or total cholesterol concentrations compared to control. The concentrations of total cholesterol, free and esterified cholesterol, triglycerides, and TBARS were increased in the macrophages of COCO-fed mice, while the content of total phospholipids did not change. The phospholipid composition showed an increase of phosphatidylcholine and a decrease of phosphatidylethanolamine. The [³H]-AA distribution in the phospholipid classes showed an increase in phosphatidylcholine and phosphatidylethanolamine. Incorporation of [³H]-cholesterol into the macrophages of COCO-fed mice and into the cholesterol ester fraction was increased. The COCO diet did not affect [³H]-AA uptake but induced an increase in [³H]-AA release. The COCO diet also enhanced AA mobilization induced by lipopolysaccharide. These results indicate that the COCO diet, high in saturated fatty acids, alters the lipid metabolism and AA turnover of peritoneal macrophages in female mice and also produces a significant degree of oxidative stress.

  9. Low-carbohydrate, high-protein, high-fat diet alters small peripheral artery reactivity in metabolic syndrome patients.

    Science.gov (United States)

    Merino, Jordi; Kones, Richard; Ferré, Raimon; Plana, Núria; Girona, Josefa; Aragonés, Gemma; Ibarretxe, Daiana; Heras, Mercedes; Masana, Luis

    2014-01-01

    Low carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or metabolic syndrome (MS), their net effect on vascular function remains unclear. Evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery vascular function, in a cohort of MS patients. This cross-sectional study included 160 MS patients. Diet was evaluated by a 3-day food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1; 45% carbohydrate, 19% protein, 31% fat) had higher saRHI values than those in the top quartile (Q4; 30% carbohydrate, 25% protein, 43% fat) (1.84±0.42 vs. 1.55±0.25, P=.012). These results were similar in T2D patients (Q1=1.779±0.311 vs. Q4=1.618±0.352, P=.011) and also in all of the MS components, except for low HDLc. Multivariate analysis demonstrated that individuals in the highest LCDS quartile, that is, consuming less carbohydrates, had a significantly negative coefficient of saRHI which was independent of confounders (HR: -0.747; 95%CI: 0.201, 0.882; P=.029). These data suggest that a dietary pattern characterized by a low amount of carbohydrate, but reciprocally higher amounts of fat and protein, is associated with poorer vascular reactivity in patients with MS and T2D. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  10. Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance.

    Science.gov (United States)

    Moreno-Navarrete, J M; Manco, M; Ibáñez, J; García-Fuentes, E; Ortega, F; Gorostiaga, E; Vendrell, J; Izquierdo, M; Martínez, C; Nolfe, G; Ricart, W; Mingrone, G; Tinahones, F; Fernández-Real, J M

    2010-02-01

    Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations. We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants). Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r=0.52, PMetabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.

  11. Characterization and mechanisms of lipid metabolism in high-fat diet ...

    African Journals Online (AJOL)

    Osumah

    fraction, there is a strong correlation between serum total cholesterol levels ... hinders extrapolation of data since fatty acids and cho- ... High fat diet-induced hyperlipidemia on viscera and blood lipid profiles. As shown in Figure 1, over a period of four weeks of feeding, the levels of serum TC, TG, LDLC, HDLC and glucose ...

  12. Glycemic index differences of high-fat diets modulate primarily lipid metabolism in murine adipose tissue

    NARCIS (Netherlands)

    Schothorst, van E.M.; Bunschoten, J.E.; Verlinde, E.; Schrauwen, P.; Keijer, J.

    2011-01-01

    A low vs. high glycemic index of a high-fat (HF) diet (LGI and HGI, respectively) significantly retarded adverse health effects in adult male C57BL/6J mice, as shown recently (Van Schothorst EM, Bunschoten A, Schrauwen P, Mensink RP, Keijer J. FASEB J 23: 1092–1101, 2009). The LGI diet enhanced

  13. Quantitative protein and fat metabolism in bull calves treated with beta-adrenergic agonist

    DEFF Research Database (Denmark)

    Chwalibog, André; Jensen, K; Thorbek, G

    1996-01-01

    Protein and energy utilization and quantitative retention of protein, fat and energy was investigated with 12 Red Danish bulls during two subsequent 6 weeks trials (Sections A and B) at a mean live weight of 195 and 335 kg respectively. Treatments were control (Group 1) and beta-agonist (L-644,96...

  14. Partial restoration of dietary fat induced metabolic adaptations to training by 7 days of carbohydrate diet

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Watt, Peter W; Richter, Erik A

    2002-01-01

    We tested the hypothesis that a shift to carbohydrate diet after prolonged adaptation to fat diet would lead to decreased glucose uptake and impaired muscle glycogen breakdown during exercise compared with ingestion of a carbohydrate diet all along. We studied 13 untrained men; 7 consumed a high-...

  15. Molecular fingerprint of high fat diet induced urinary bladder metabolic dysfunction in a rat model.

    Directory of Open Access Journals (Sweden)

    Andreas Oberbach

    Full Text Available AIMS/HYPOTHESIS: Diabetic voiding dysfunction has been reported in epidemiological dimension of individuals with diabetes mellitus. Animal models might provide new insights into the molecular mechanisms of this dysfunction to facilitate early diagnosis and to identify new drug targets for therapeutic interventions. METHODS: Thirty male Sprague-Dawley rats received either chow or high-fat diet for eleven weeks. Proteomic alterations were comparatively monitored in both groups to discover a molecular fingerprinting of the urinary bladder remodelling/dysfunction. Results were validated by ELISA, Western blotting and immunohistology. RESULTS: In the proteome analysis 383 proteins were identified and canonical pathway analysis revealed a significant up-regulation of acute phase reaction, hypoxia, glycolysis, β-oxidation, and proteins related to mitochondrial dysfunction in high-fat diet rats. In contrast, calcium signalling, cytoskeletal proteins, calpain, 14-3-3η and eNOS signalling were down-regulated in this group. Interestingly, we found increased ubiquitin proteasome activity in the high-fat diet group that might explain the significant down-regulation of eNOS, 14-3-3η and calpain. CONCLUSIONS/INTERPRETATION: Thus, high-fat diet is sufficient to induce significant remodelling of the urinary bladder and alterations of the molecular fingerprint. Our findings give new insights into obesity related bladder dysfunction and identified proteins that may indicate novel pathophysiological mechanisms and therefore constitute new drug targets.

  16. Unexpected relationship between fat mass and basal metabolic rate in pregnant women.

    Science.gov (United States)

    Bronstein, M N; Mak, R P; King, J C

    1996-05-01

    We investigated the relationships between BMR, fat-free mass (FFM) and fat mass in pregnancy. BMR was measured by indirect calorimetry and body composition was assessed by densitometry in seventeen non-pregnant women (79.9 (SD 26.3, range 50.5-151.4) kg) and sixteen pregnant women (75.7 (SD 20.6, range 54.5-115.9) kg). The pregnant women were evaluated during weeks 31-35 of gestation. Multiple regression analysis of BMR with FFM and fat mass in the non-pregnant women showed that FFM was a highly significant predictor of BMR (P relationships of BMR with FFM and fat mass differ significantly in non-pregnant and pregnant women. It is proposed that pregnancy represents a unique condition during which BMR is regulated by maternal adipose reserves. An augmented BMR in overweight pregnant women may be protective, given that excessive weight gain may be detrimental to neonatal and maternal health.

  17. Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

    Czech Academy of Sciences Publication Activity Database

    Pepino, M. Y.; Kuda, Ondřej; Samovski, D.; Abumrad, N. A.

    2014-01-01

    Roč. 34, JULY (2014), s. 281-303 ISSN 0199-9885 R&D Projects: GA ČR(CZ) GP13-04449P Institutional support: RVO:67985823 Keywords : fat taste * chylomicron * VLDL * CCK * secretin * calcium * FA binding * phospholipase * eicosanoid Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.359, year: 2014

  18. Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption

    Science.gov (United States)

    Bergen, Andrew W.; Michel, Martha; Nishita, Denise; Krasnow, Ruth; Javitz, Harold S.; Conneely, Karen N.; Lessov-Schlaggar, Christina N.; Hops, Hyman; Zhu, Andy Z. X.; Baurley, James W.; McClure, Jennifer B.; Hall, Sharon M.; Baker, Timothy B.; Conti, David V.; Benowitz, Neal L.; Lerman, Caryn; Tyndale, Rachel F.; Swan, Gary E.

    2015-01-01

    The Nicotine Metabolite Ratio (NMR, ratio of trans-3’-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis. PMID:26132489

  19. Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.

    Directory of Open Access Journals (Sweden)

    Andrew W Bergen

    Full Text Available The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine, has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3. Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis.

  20. Comparison of metabolic profile and abdominal fat distribution between karyotypically normal women with premature ovarian insufficiency and age matched controls.

    Science.gov (United States)

    Ates, Seda; Yesil, Gozde; Sevket, Osman; Molla, Taner; Yildiz, Seyma

    2014-11-01

    We designed a prospective case-control study in order to investigate the lipid profiles, insulin sensitivity, presence of metabolic syndrome (MetS) and the abdominal fat distribution in karyotypically normal women with premature ovarian insufficiency (POI). Anthropometric measurements, FSH, estradiol, total testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI), fasting glucose and insulin, homeostatic model for insulin resistance (HOMA-IR), lipid profile, the prevalence of MetS and ultrasonographic abdominal fat measurements were assessed in 56 women with POI and 59 healthy controls at the same age range. Serum levels of T, SHBG and FAI were not significantly different between both groups. Total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were higher in women with POI. There were no differences in glucose, insulin, HOMA-IR, low-density lipoprotein cholesterol (LDL-C), triglyceride levels between the two groups. A significant positive correlation was identified between T and TG and also between FAI and LDL-C; SHBG levels were correlated inversely with FSH, and positively with HDL-C in women with POI. The presence of MetS was significantly higher in women with POI. The subcutaneous, preperitoneal and visceral fat thicknesses were not significantly different between the groups. Early cessation of ovulatory function may associated with higher levels of serum TC and HDL-C, but does not seem to cause differences in abdominal fat distribution in women with POI. POI is associated with higher risk of MetS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Feeding oxidized fat during pregnancy up-regulates expression of PPARα-responsive genes in the liver of rat fetuses

    Directory of Open Access Journals (Sweden)

    Brandsch Corinna

    2007-03-01

    Full Text Available Abstract Background Feeding oxidized fats causes activation of peroxisome proliferator-activated receptor α (PPARα in the liver of rats. However, whether feeding oxidized fat during pregnancy also results in activation of PPARα in fetal liver is unknown. Thus, this study aimed to explore whether feeding oxidized fat during pregnancy causes a PPARα response in fetal liver. Two experiments with pregnant rats which were administered three different diets (control; oxidized fat; clofibrate as positive control in a controlled feeding regimen during either late pregnancy (first experiment or whole pregnancy (second experiment were performed. Results In both experiments pregnant rats treated with oxidized fat or clofibrate had higher relative mRNA concentrations of the PPARα-responsive genes acyl-CoA oxidase (ACO, cytochrome P450 4A1 (CYP4A1, L-type carnitin-palmitoyl transferase I (L-CPT I, medium-chain acyl-CoA dehydrogenase (MCAD, and long-chain acyl-CoA dehydrogenase (LCAD in the liver than control rats (P P P Conclusion The present study demonstrates for the first time that components of oxidized fat with PPARα activating potential are able to induce a PPARα response in the liver of fetuses. Moreover, the present study shows that feeding oxidized fat during whole pregnancy, but not during late pregnancy, lowers triacylglycerol concentrations in fetal livers.

  2. Estimating the continuous-time dynamics of energy and fat metabolism in mice.

    Directory of Open Access Journals (Sweden)

    Juen Guo

    2009-09-01

    Full Text Available The mouse has become the most popular organism for investigating molecular mechanisms of body weight regulation. But understanding the physiological context by which a molecule exerts its effect on body weight requires knowledge of energy intake, energy expenditure, and fuel selection. Furthermore, measurements of these variables made at an isolated time point cannot explain why body weight has its present value since body weight is determined by the past history of energy and macronutrient imbalance. While food intake and body weight changes can be frequently measured over several weeks (the relevant time scale for mice, correspondingly frequent measurements of energy expenditure and fuel selection are not currently feasible. To address this issue, we developed a mathematical method based on the law of energy conservation that uses the measured time course of body weight and food intake to estimate the underlying continuous-time dynamics of energy output and net fat oxidation. We applied our methodology to male C57BL/6 mice consuming various ad libitum diets during weight gain and loss over several weeks and present the first continuous-time estimates of energy output and net fat oxidation rates underlying the observed body composition changes. We show that transient energy and fat imbalances in the first several days following a diet switch can account for a significant fraction of the total body weight change. We also discovered a time-invariant curve relating body fat and fat-free masses in male C57BL/6 mice, and the shape of this curve determines how diet, fuel selection, and body composition are interrelated.

  3. Metabolic syndrome, diabetes and atherosclerosis: Influence of gene-environment interaction

    Energy Technology Data Exchange (ETDEWEB)

    Andreassi, Maria Grazia, E-mail: andreas@ifc.cnr.it [CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Via Aurelia Sud, Massa (Italy)

    2009-07-10

    Despite remarkable progress in diagnosis and understanding of risk factors, cardiovascular disease (CVD) remains still the leading cause of morbidity and mortality in the world's developed countries. The metabolic syndrome, a cluster of risk factors (visceral obesity, insulin resistance, dyslipidaemia, and hypertension), is increasingly being recognized as a new risk factor for type 2 diabetes and atherosclerotic cardiovascular disease. Nevertheless, there is wide variation in both the occurrence of disease and age of onset, even in individuals who display very similar risk profiles. There is now compelling evidence that a complex interplay between genetic determinants and environmental factors (still largely unknown) is the reason for this large inter-individual variation in disease susceptibility. The purpose of the present review is to describe the current status of our knowledge concerning the gene-environment interactions potentially implicated in the pathogenesis of metabolic syndrome, diabetes and cardiovascular disease. It focuses predominantly on studies of genes (peroxisome proliferator-activated receptor-gamma, alcohol dehydrogenase type 1C, apolipoprotein E, glutathione S-transferases T1 and M1) that are known to be modified by dietary and lifestyle habits (fat diet, intake of alcohol and smoking habit). It also describes the limited current understanding of the role of genetic variants of xenobiotic metabolizing enzymes and their interactions with environmental toxicants. Additional studies are needed in order to clarify whether inter-individual differences in detoxification of environmental toxicants may have an essential role in the development of CVD and contribute to the emerging field of 'environmental cardiology'. Such knowledge may be particularly relevant for improving cardiovascular risk stratification and conceiving the development of 'personalized intervention program'.

  4. Modulatory effects of Caralluma fimbriata extract against high-fat diet induced abnormalities in carbohydrate metabolism in Wistar rats.

    Science.gov (United States)

    Gujjala, Sudhakara; Putakala, Mallaiah; Nukala, Srinivasulu; Bangeppagari, Manjunatha; Rajendran, Ramaswamy; Desireddy, Saralakumari

    2017-08-01

    The present study was aimed to evaluate the modulatory effects of hydroalcoholic extract of Caralluma fimbriata (CFE) by assaying the activities of key enzymes of carbohydrate metabolism and changes in glycogen content (liver and muscle) in high-fat (HF) diet-induced diabetic rats. In vitro glucose uptake studies were carried out in both psoas muscle and adipose tissue. The inhibitory effect of the extract on α-amylase was determined in in vitro studies. Male Wistar rats of body weight around 180g were divided into five groups (n=8), two of these groups were fed with standard pellet diet and the other three groups were fed with HF- (60%) diet. CFE (200mg/kg body weight/day) was administered through oral route to each group of standard pellet diet rats and HF-fed rats and Metformin (Met) (20mg/kg body weight/day) was administered through oral route to HFD+Met group for 90 days. At the end of the experimental period, biochemical parameters related to glycogen content in liver and muscle, and intestinal disaccharidases like maltase, sucrase and lactase were assayed. Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphorfructoki nase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase), intestinal disaccharidases and glycogen content as observed in the high fat diet-fed rats were prevented with CFE/Met administration. From this study, we observed that CFE/Met could significantly restore the levels of glycogen in liver and muscle and key enzymes of carbohydrate metabolism to near normal in groups-HFD+CFE and HFD+Met. The skeletal muscle of HF-diet fed rats showed degenerative changes of muscle myofibers with fat deposition. These changes were attenuated in the HFD group treated with CFE/Met and retained their normal structure appearance. It can be concluded from these results that CFE might be of value in reducing the alterations related to carbohydrate metabolism under high calorie

  5. Change in proportional protein intake in a 10-week energy-restricted low- or high-fat diet, in relation to changes in body size and metabolic factors

    DEFF Research Database (Denmark)

    Stocks, Tanja; Taylor, Moira A; Ängquist, Lars

    2013-01-01

    Objective: To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. Methods: Obese adults (n = 771) were randomised to a 600 kcal...... energy-deficient low-fat (20-25 fat%) or high-fat (40-45 fat%) diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (2) on outcomes....... Results: The low-fat group with >2 prot% increase lost 1.1 kg more weight (p = 0.03) and reduced cholesterol by 0.25 mmol/l more (p = 0.003) than the high-fat group with >2 prot% decrease. These differences were 2.5-fold and 1.8-fold greater than the differences between the low-fat and high-fat groups...

  6. Identifying genes and gene networks involved in chromium metabolism and detoxification in Crambe abyssinica

    Energy Technology Data Exchange (ETDEWEB)

    Zulfiqar, Asma, E-mail: asmazulfiqar08@yahoo.com [Department of Plant, Soil, and Insect Sciences, 270 Stockbridge Road, University of Massachusetts Amherst, MA 01003 (United States); Paulose, Bibin, E-mail: bpaulose@psis.umass.edu [Department of Plant, Soil, and Insect Sciences, 270 Stockbridge Road, University of Massachusetts Amherst, MA 01003 (United States); Chhikara, Sudesh, E-mail: sudesh@psis.umass.edu [Department of Plant, Soil, and Insect Sciences, 270 Stockbridge Road, University of Massachusetts Amherst, MA 01003 (United States); Dhankher, Om Parkash, E-mail: parkash@psis.umass.edu [Department of Plant, Soil, and Insect Sciences, 270 Stockbridge Road, University of Massachusetts Amherst, MA 01003 (United States)

    2011-10-15

    Chromium pollution is a serious environmental problem with few cost-effective remediation strategies available. Crambe abyssinica (a member of Brassicaseae), a non-food, fast growing high biomass crop, is an ideal candidate for phytoremediation of heavy metals contaminated soils. The present study used a PCR-Select Suppression Subtraction Hybridization approach in C. abyssinica to isolate differentially expressed genes in response to Cr exposure. A total of 72 differentially expressed subtracted cDNAs were sequenced and found to represent 43 genes. The subtracted cDNAs suggest that Cr stress significantly affects pathways related to stress/defense, ion transporters, sulfur assimilation, cell signaling, protein degradation, photosynthesis and cell metabolism. The regulation of these genes in response to Cr exposure was further confirmed by semi-quantitative RT-PCR. Characterization of these differentially expressed genes may enable the engineering of non-food, high-biomass plants, including C. abyssinica, for phytoremediation of Cr-contaminated soils and sediments. - Highlights: > Molecular mechanism of Cr uptake and detoxification in plants is not well known. > We identified differentially regulated genes upon Cr exposure in Crambe abyssinica. > 72 Cr-induced subtracted cDNAs were sequenced and found to represent 43 genes. > Pathways linked to stress, ion transport, and sulfur assimilation were affected. > This is the first Cr transcriptome study in a crop with phytoremediation potential. - This study describes the identification and isolation of differentially expressed genes involved in chromium metabolism and detoxification in a non-food industrial oil crop Crambe abyssinica.

  7. [Effect of high-fat diet and food restriction on energy metabolism in obesity-prone and obesity-resistant rats].

    Science.gov (United States)

    Liu, Jianmin; Wang, Junxia; Zheng, Long; Lian, Weiguang; Liu, Shufeng

    2015-09-01

    To explore the effect of high-fat diet and food restriction on energy metabolism in obesity-prone (OP) and obesity-resistant (OR) rats. Sixty male Sprague-Dawley (SD) rats were divided into OP, OR and control groups according to their body weight gain after fed with high-fat diet for 3 wk. OP and OR groups were fed with high-fat diet in the following 12 wk to promote the development of obesity. Then one-half of the rats of each group began to food restriction and were allowed access to 50% of their individual baseline mean daily food intake each day, while the other half were maintained on ad libitum food for 2 wk. Basal metabolic rate (BMR), resting metabolic rate (RMR) of each group were measured by indirect calorimetry during the high-fat diet feeding and food restriction conditions. After the rats were sacrificed, body fat content was measured. OR rats had significantly higher BMR and RMR than the other two groups during high-fat diet feeding condition. There was no significant difference between OP and control group. Food restriction led to a reduction in BMR and RMR in all groups. OR rats showed a significantly greater reduction. OP group showed a significant decrease in body fat weight and fat content during the food restriction period, while there was no significant differences in OR rats. There are significant differences between OP and OR rats in BMR and RMR either in high-fat diet feeding condition or food restricted state. OR rat has the ability to sense and respond to energy imbalance more accurately than OP rat.

  8. Differential roles of breakfast only (one meal per day and a bigger breakfast with a small dinner (two meals per day in mice fed a high-fat diet with regard to induced obesity and lipid metabolism

    Directory of Open Access Journals (Sweden)

    Fuse Yuta

    2012-05-01

    Full Text Available Abstract Background Recent studies on humans and rodents have suggested that the timing of food intake plays an important role in circadian regulation and metabolic health. Consumption of high-fat foods during the inactive period or at the end of the awake period results in weight gain and metabolic syndrome in rodents. However, the distinct effects of breakfast size and the breakfast/dinner size ratio on metabolic health have not yet been fully examined in mice. Methods We examined whether the parameters of metabolic syndrome were differentially affected in mice that consumed a large meal at the beginning of the awake period (breakfast; one meal group and a relatively smaller meal at end of the awake period (dinner; two meals group. The mice of each group were provided equal food volume per day. Results Mice on one meal exhibited an increase in body weight gain, hyperinsulinemia, hyperleptinemia, and a decrease of gene expression associated with β-oxidation in adipose tissue and liver compared with those on two meals. The circadian expression pattern of the Clock gene in mice on one meal was disturbed compared with those on two meals. Conclusions In conclusion, a bigger breakfast with a smaller dinner (two meals per day but not breakfast only (one meal per day helps control body weight and fat accumulation in mice on a high-fat meals schedule. The findings of this study suggest that dietary recommendations for weight reduction and/or maintenance should include information on the timing and quantity of dietary intake.

  9. Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters.

    Directory of Open Access Journals (Sweden)

    Virginie Lecomte

    Full Text Available The gut microbiota is emerging as a new factor in the development of obesity. Many studies have described changes in microbiota composition in response to obesity and high fat diet (HFD at the phylum level. In this study we used 16s RNA high throughput sequencing on faecal samples from rats chronically fed HFD or control chow (n = 10 per group, 16 weeks to investigate changes in gut microbiota composition at the species level. 53.17% dissimilarity between groups was observed at the species level. Lactobacillus intestinalis dominated the microbiota in rats under the chow diet. However this species was considerably less abundant in rats fed HFD (P<0.0001, this being compensated by an increase in abundance of propionate/acetate producing species. To further understand the influence of these species on the development of the obese phenotype, we correlated their abundance with metabolic parameters associated with obesity. Of the taxa contributing the most to dissimilarity between groups, 10 presented significant correlations with at least one of the tested parameters, three of them correlated positively with all metabolic parameters: Phascolarctobacterium, Proteus mirabilis and Veillonellaceae, all propionate/acetate producers. Lactobacillus intestinalis was the only species whose abundance was negatively correlated with change in body weight and fat mass. This species decreased drastically in response to HFD, favouring propionate/acetate producing bacterial species whose abundance was strongly correlated with adiposity and deterioration of metabolic factors. Our observations suggest that these species may play a key role in the development of obesity in response to a HFD.

  10. Cutoff Values of the Body Fat Mass and Visceral Adiposity for the Prediction of Metabolic Syndrome in a sample of Colombian University Students

    OpenAIRE

    Romero Tovar, Lorena Isabel

    2017-01-01

    Background: Visceral obesity and high body fat percentages are related to metabolic syndrome (MetS) in all ethnic groups. Based on the International Diabetes Federation (IDF) definition of MetS, the aim of the study was to explore thresholds of body fat (BF%) and the visceral fat area (VFA) for the prediction of MetS among Colombian university students. Methods: A cross-sectional study was conducted on 886 volunteers (51.9% women, mean age= 21.4 years). Weight, height, serum lipids indices, b...

  11. Long-term high-physiological-dose growth hormone reduces intra-abdominal fat in HIV-infected patients with a neutral effect on glucose metabolism

    DEFF Research Database (Denmark)

    Hansen, B R; Haugaard, S B; Jensen, Frank Krieger

    2010-01-01

    OBJECTIVES: The aim of the study was to investigate the effect of long-term high-physiological-dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV-infected patients. METHODS: Forty-six HIV-infected Caucasian men on highly active antiretroviral......, glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention. CONCLUSIONS: Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV-infected patients. This treatment appeared to be safe with respect to glucose...

  12. The Variability of Growth Hormone Gene Associated with Ultrasound Imaging of Longissimus dorsi Muscle and Perirenal Fat in Rabbits

    Directory of Open Access Journals (Sweden)

    T. I. Amalianingsih

    2014-04-01

    Full Text Available Identification of genes in rabbits correlated to economic traits were intended to improve and develop their genetic quality. The objective of this research was to analyze the variability of growth hormone gene (GH in three rabbit breeds, i.e. Rex, Satin, and Reza (Rex and Satin crosses then was associated with ultrasound imaging of Longissimus dorsi muscle and perirenal fat thickness. Identification of the variability of growth hormone gene was analyzed using PCR RFLP technique from blood samples of 33 mature male rabbits in Indonesian Research Institute for Animal Production (IRIAP. Thickness of Longissimus dorsi muscle and perirenal fat were imaged and measured by using ultrasound unit at 2nd to 3rd lumbar vertebrae in the left body side. PCR product of GH gene fragment (231 base pair /bp was digested with restriction enzyme Bsh1236I. PCR-RFLP patterns were allele T resulted in an undigested fragment of 231 bp; allele C resulted in fragment of 169 bp and 62 bp. The result showed that Bsh1236I GH gene had three genotypes, i.e. CC, TT, and CT. There were signifficant association of Longissimus dorsi muscle thickness between rabbit breed (P<0.05. There was no significant association between GH Bsh1236I gene polymorphism and imaging ultrasound of Longissimus dorsi muscle and perirenal fat thickness. The association of characteristic genotype of GH|Bsh1236I gene with measurement phenotype was not significant, however it had potency as marker assisted selection (MAS.

  13. Regional fat metabolism in human splanchnic and adipose tissues; the effect of exercise

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Bülow, Jens; Sacchetti, Massimo

    2002-01-01

    This study was conducted to investigate the role of splanchnic and adipose tissue in the regulation of fatty acid (FA) metabolism at rest, during 1 h of semi-recumbent cycle exercise at 60 % of maximal power output and 3 h of recovery. In six post-absorptive healthy volunteers catheters were placed...... in a radial artery, hepatic vein and a subcutaneous vein on the anterior abdominal wall. Whole body, and regional splanchnic and adipose tissue FA metabolism were measured by a constant infusion of the stable isotopes [U-(13)C]palmitate and [(2)H(5)]glycerol and according to Fick's principle. The whole body...... that adipose tissue can metabolize glycerol....

  14. A functional genetic variant in fragile-site gene FATS modulates the risk of breast cancer in triparous women

    International Nuclear Information System (INIS)

    Song, Fangfang; Zhang, Jun; Qiu, Li; Zhao, Yawen; Xing, Pan; Lu, Jiachun; Chen, Kexin; Li, Zheng

    2015-01-01

    The fragile-site associated tumor suppressor (FATS, formerly known as C10orf90), a regulator of p53-p21 pathway has been involved in the onset of breast cancer. Recent data support the idea that the crosstalk between FATS and p53 may be of physiological importance for reproduction during evolution. The aim of the current study was to test the hypothesis that FATS genetic polymorphism can influence the risk of breast cancer. We conducted population-based studies in two independent cohorts comprising 1 532 cases and 1 573 controls in Tianjin of North China, and 804 cases and 835 controls in Guangzhou of South China, coupled with functional validation methods, to investigate the role of FATS genetic variant in breast cancer risk. We identified a functional variant rs11245007 (905C > T, 262D/N) in fragile-site gene FATS that modulates p53 activation. FATS-262 N exhibited stronger E3 activity to polyubiquitinate p53 than did FATS-262D, leading to the stronger transcriptional activity of p53 and more pronounced stabilization of p53 protein and its activation in response to DNA damage. Case–control studies found that CT or TT genotype was significantly associated with a protective effect on breast cancer risk in women with parity ≥ 3, which was not affected by family history. Our findings suggest the role of FATS-p53 signaling cascade in suppressing pregnancy-related carcinogenesis and potential application of FATS genotyping in breast cancer prevention. The online version of this article (doi:10.1186/s12885-015-1570-9) contains supplementary material, which is available to authorized users

  15. Feeding oxidized fat during pregnancy up-regulates expression of PPARα-responsive genes in the liver of rat fetuses

    Science.gov (United States)

    Ringseis, Robert; Gutgesell, Anke; Dathe, Corinna; Brandsch, Corinna; Eder, Klaus

    2007-01-01

    Background Feeding oxidized fats causes activation of peroxisome proliferator-activated receptor α (PPARα) in the liver of rats. However, whether feeding oxidized fat during pregnancy also results in activation of PPARα in fetal liver is unknown. Thus, this study aimed to explore whether feeding oxidized fat during pregnancy causes a PPARα response in fetal liver. Two experiments with pregnant rats which were administered three different diets (control; oxidized fat; clofibrate as positive control) in a controlled feeding regimen during either late pregnancy (first experiment) or whole pregnancy (second experiment) were performed. Results In both experiments pregnant rats treated with oxidized fat or clofibrate had higher relative mRNA concentrations of the PPARα-responsive genes acyl-CoA oxidase (ACO), cytochrome P450 4A1 (CYP4A1), L-type carnitin-palmitoyl transferase I (L-CPT I), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) in the liver than control rats (P < 0.05). In addition, in both experiments fetuses of the oxidized fat group and the clofibrate group also had markedly higher relative mRNA concentrations of ACO, CYP4A1, CPT I, MCAD, and LCAD in the liver than those of the control group (P < 0.05), whereas the relative mRNA concentrations of PPARα, SREBP-1c, and FAS did not differ between treatment groups. In the second experiment treatment with oxidized fat also reduced triacylglycerol concentrations in the livers of pregnant rats and fetuses (P < 0.05). Conclusion The present study demonstrates for the first time that components of oxidized fat with PPARα activating potential are able to induce a PPARα response in the liver of fetuses. Moreover, the present study shows that feeding oxidized fat during whole pregnancy, but not during late pregnancy, lowers triacylglycerol concentrations in fetal livers. PMID:17352811

  16. Feeding oxidized fat during pregnancy up-regulates expression of PPARalpha-responsive genes in the liver of rat fetuses.

    Science.gov (United States)

    Ringseis, Robert; Gutgesell, Anke; Dathe, Corinna; Brandsch, Corinna; Eder, Klaus

    2007-03-12

    Feeding oxidized fats causes activation of peroxisome proliferator-activated receptor alpha (PPARalpha) in the liver of rats. However, whether feeding oxidized fat during pregnancy also results in activation of PPARalpha in fetal liver is unknown. Thus, this study aimed to explore whether feeding oxidized fat during pregnancy causes a PPARalpha response in fetal liver. Two experiments with pregnant rats which were administered three different diets (control; oxidized fat; clofibrate as positive control) in a controlled feeding regimen during either late pregnancy (first experiment) or whole pregnancy (second experiment) were performed. In both experiments pregnant rats treated with oxidized fat or clofibrate had higher relative mRNA concentrations of the PPARalpha-responsive genes acyl-CoA oxidase (ACO), cytochrome P450 4A1 (CYP4A1), L-type carnitin-palmitoyl transferase I (L-CPT I), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) in the liver than control rats (P < 0.05). In addition, in both experiments fetuses of the oxidized fat group and the clofibrate group also had markedly higher relative mRNA concentrations of ACO, CYP4A1, CPT I, MCAD, and LCAD in the liver than those of the control group (P < 0.05), whereas the relative mRNA concentrations of PPARalpha, SREBP-1c, and FAS did not differ between treatment groups. In the second experiment treatment with oxidized fat also reduced triacylglycerol concentrations in the livers of pregnant rats and fetuses (P < 0.05). The present study demonstrates for the first time that components of oxidized fat with PPARalpha activating potential are able to induce a PPARalpha response in the liver of fetuses. Moreover, the present study shows that feeding oxidized fat during whole pregnancy, but not during late pregnancy, lowers triacylglycerol concentrations in fetal livers.

  17. A novel AAT-deletion mutation in the coding sequence of the BCO2 gene in yellow-fat rabbits.

    Science.gov (United States)

    Strychalski, Janusz; Brym, Paweł; Czarnik, Urszula; Gugołek, Andrzej

    2015-11-01

    The carcasses of yellow-fat rabbits may be attractive to modern consumers, because they have a relatively high content of biologically active compounds. One of the main candidate genes associated with the yellow-fat trait is β-carotene 9',10'-oxygenase (BCO2). This study is the first report of the novel AAT-deletion mutation at codon 248 of the BCO2 gene, which has been found in homozygous yellow-fat rabbits. The deletion mutation, located at the beginning of exon 6, results in the absence of asparagine in protein. We also developed a PCR-RFLP test that supports intravital genotyping of indel polymorphism based on genomic DNA.

  18. Maternal High-Fat-Diet Programs Rat Offspring Liver Fatty Acid Metabolism

    OpenAIRE

    Seet, Emily L.; Yee, Jennifer K.; Jellyman, Juanita K.; Han, Guang; Ross, Michael G.; Desai, Mina

    2015-01-01

    In offspring exposed in utero to a maternal diet high in fat (HF), we have previously demonstrated that despite similar birth weights, HF adult offspring at 6 months of age had significantly higher body weights, greater adiposity, and increased triacylglycerol (TAG) levels as compared to controls. We hypothesized that a maternal HF diet predisposes to offspring adiposity via a programmed increase in the synthesis of monounsaturated fatty acids in the liver and hence increased substrate availa...

  19. Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Yan Y Lam

    Full Text Available We investigated the relationship between gut health, visceral fat dysfunction and metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or high saturated fat diet (HFD. Circulating glucose, insulin and inflammatory markers were measured. Proximal colon barrier function was assessed by measuring transepithelial resistance and mRNA expression of tight-junction proteins. Gut microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis factor (TNF-α and interleukin (IL-6 mRNA levels were measured in proximal colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration (F4/80⁺ was assessed using immunohistochemical staining. HFD mice had a higher insulin/glucose ratio (P = 0.020 and serum levels of serum amyloid A3 (131%; P = 0.008 but reduced circulating adiponectin (64%; P = 0.011. In proximal colon of HFD mice compared to mice fed the control diet, transepithelial resistance and mRNA expression of zona occludens 1 were reduced by 38% (P<0.001 and 40% (P = 0.025 respectively and TNF-α mRNA level was 6.6-fold higher (P = 0.037. HFD reduced Lactobacillus (75%; P<0.001 but increased Oscillibacter (279%; P = 0.004 in fecal microbiota. Correlations were found between abundances of Lactobacillus (r = 0.52; P = 0.013 and Oscillibacter (r = -0.55; P = 0.007 with transepithelial resistance of the proximal colon. HFD increased macrophage infiltration (58%; P = 0.020, TNF-α (2.5-fold, P<0.001 and IL-6 mRNA levels (2.5-fold; P = 0.008 in mesenteric fat. Increased macrophage infiltration in epididymal fat was also observed with HFD feeding (71%; P = 0.006 but neither TNF-α nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed no signs of inflammation in HFD mice. The current results implicate gut dysfunction, and attendant inflammation of contiguous adipose, as salient features of the metabolic dysregulation of diet-induced obesity.

  20. Catechins and Caffeine Inhibit Fat Accumulation in Mice through the Improvement of Hepatic Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Chikako Sugiura

    2012-01-01

    Full Text Available To elucidate the inhibiting mechanisms of fat accumulation by catechins, caffeine, and epigallocatechin gallate (EGCG, ICR mice were fed diets containing either 0.3% catechins or 0.1% EGCG and/or 0.05% caffeine for 4 weeks. After the feeding, intraperitoneal adipose tissues weights were significantly lower in the caffeine, catechins + caffeine, and EGCG + caffeine groups compared to controls. Hepatic fatty acid synthase (FAS activity in the catechins + caffeine group was significantly lower, and the activities of acyl-CoA oxidase (ACO and carnitine palmitoyltransferase-II (CPT-II were significantly higher, compared to the control group. However, these activities were not observed in the other groups. FAS mRNA expression levels in the catechins + caffeine group were significantly lower than in the control group. ACO and CPT-II mRNA levels were not different among all of the treatment groups. These findings indicate that the inhibitory effects of fat accumulation via a combination of catechins, EGCG, or caffeine were stronger collectively than by either catechins, EGCG, or caffeine alone. Moreover, it was demonstrated that the combination of catechins and caffeine induced inhibition of fat accumulation by suppression of fatty acid synthesis and upregulation of the enzymatic activities involved in β-oxidation of fatty acid in the liver, but this result was not observed by combination of EGCG and caffeine.

  1. Gene expression in plant lipid metabolism in Arabidopsis seedlings.

    Directory of Open Access Journals (Sweden)

    An-Shan Hsiao

    Full Text Available Events in plant lipid metabolism are important during seedling establishment. As it has not been experimentally verified whether lipid metabolism in 2- and 5-day-old Arabidopsis thaliana seedlings is diurnally-controlled, quantitative real-time PCR analysis was used to investigate the expression of target genes in acyl-lipid transfer, β-oxidation and triacylglycerol (TAG synthesis and hydrolysis in wild-type Arabidopsis WS and Col-0. In both WS and Col-0, ACYL-COA-BINDING PROTEIN3 (ACBP3, DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1 and DGAT3 showed diurnal control in 2- and 5-day-old seedlings. Also, COMATOSE (CTS was diurnally regulated in 2-day-old seedlings and LONG-CHAIN ACYL-COA SYNTHETASE6 (LACS6 in 5-day-old seedlings in both WS and Col-0. Subsequently, the effect of CIRCADIAN CLOCK ASSOCIATED1 (CCA1 and LATE ELONGATED HYPOCOTYL (LHY from the core clock system was examined using the cca1lhy mutant and CCA1-overexpressing (CCA1-OX lines versus wild-type WS and Col-0, respectively. Results revealed differential gene expression in lipid metabolism between 2- and 5-day-old mutant and wild-type WS seedlings, as well as between CCA1-OX and wild-type Col-0. Of the ACBPs, ACBP3 displayed the most significant changes between cca1lhy and WS and between CCA1-OX and Col-0, consistent with previous reports that ACBP3 is greatly affected by light/dark cycling. Evidence of oil body retention in 4- and 5-day-old seedlings of the cca1lhy mutant in comparison to WS indicated the effect of cca1lhy on storage lipid reserve mobilization. Lipid profiling revealed differences in primary lipid metabolism, namely in TAG, fatty acid methyl ester and acyl-CoA contents amongst cca1lhy, CCA1-OX, and wild-type seedlings. Taken together, this study demonstrates that lipid metabolism is subject to diurnal regulation in the early stages of seedling development in Arabidopsis.

  2. High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice.

    Science.gov (United States)

    Zemdegs, Juliane; Quesseveur, Gaël; Jarriault, David; Pénicaud, Luc; Fioramonti, Xavier; Guiard, Bruno P

    2016-07-01

    The link between type 2 diabetes mellitus (T2DM) and depression is bidirectional. However, the possibility that metabolic disorders may elicit anxiogenic-like/depressive-like symptoms or alter the efficacy of antidepressant drugs remains poorly documented. This study explored the influence of T2DM on emotionality and proposed a therapeutic strategy that might be used in depressed diabetic patients. Mice were fed a high-fat diet (HFD) and subjected to a full comprehensive metabolic and behavioural analysis to establish correlations between metabolic and psychiatric disorders. In vivo intra-hippocampal microdialysis was also applied to propose a mechanism underpinning the phenotype of mice fed the HFD. Finally, we tested whether chronic administration of the selective 5-HT reuptake inhibitor escitalopram or HFD withdrawal could reverse HFD-induced metabolic and behavioural anomalies. The increased body weight, hyperglycaemia and impaired glucose tolerance in response to HFD were correlated with anxiogenic-like/depressive-like symptoms. Moreover, this phenotype was associated with decreased extracellular 5-HT levels in the hippocampus which may result from increased sensitivity of the dorsal raphe 5-HT1A autoreceptor. Interestingly, the beneficial effect of prolonged administration of escitalopram was abolished in HFD-fed mice. On the contrary, HFD withdrawal completely reversed metabolic impairments and positively changed symptoms of anxiety, although some behavioural anomalies persisted. Our data provide clear-cut evidence that both pathologies are finely correlated and associated with impaired 5-HT mediated neurotransmission in the hippocampus. Further experiments are warranted to define the most adequate strategy for the treatment of such co-morbidity. This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminerg