Changes in rat liver and adipose tissue lipogenesis after single lethal X-irradiation: modification by the restricted food intake

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Sedlakova, A; Ahlers, I; Praslicka, M [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie

1981-01-01

Male rats of Wistar strain were adapted during a 4-week period to the nutritional regimes of meal feeding (MF) and ad libitum (AL) and were irradiated with the single whole-body lethal X-ray dose 14.35 Gy after 22 h of fasting. Within the intervals 1, 24, 48 and 72 h after irradiation lipogenesis changes in the liver were studied by measuring 1-/sup 14/C-acetate incorporation (74 KBq) in the total lipids, fatty acids and cholesterol, and in the white adipose tissue pieces by measuring U-/sup 14/C-glucose incorporation (74 KBq) in the total lipids, fatty acids and glyceride glycerol. Lipogenesis increased in the liver of the irradiated rats as compared with sham irradiated rats and reached the maximal values at 72 h after irradiation in AL animals and at 48 h after irradiation in MF animals. Lipogenesis in the adipose tissue decreased in the irradiated rats as compared with the sham irradiated ones and continued to decrease with the post-irradiation period. The adaptation to the nutritional regime of meal feeding markedly modified lipogenesis in the liver and the adipose tissue of the irradiated rats. Long-term fasting (before and after irradiation) was supposed to be another modifying factor in the lipogenesis changes. Lipogenesis changes in the liver depended on the MF nutritional regime.

Alcohol, Adipose Tissue and Lipid Dysregulation

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Jennifer L. Steiner

2017-02-01

Full Text Available Chronic alcohol consumption perturbs lipid metabolism as it increases adipose tissue lipolysis and leads to ectopic fat deposition within the liver and the development of alcoholic fatty liver disease. In addition to the recognition of the role of adipose tissue derived fatty acids in liver steatosis, alcohol also impacts other functions of adipose tissue and lipid metabolism. Lipid balance in response to long‐term alcohol intake favors adipose tissue loss and fatty acid efflux as lipolysis is upregulated and lipogenesis is either slightly decreased or unchanged. Study of the lipolytic and lipogenic pathways has identified several regulatory proteins modulated by alcohol that contribute to these effects. Glucose tolerance of adipose tissue is also impaired by chronic alcohol due to decreased glucose transporter‐4 availability at the membrane. As an endocrine organ, white adipose tissue (WAT releases several adipokines that are negatively modulated following chronic alcohol consumption including adiponectin, leptin, and resistin. When these effects are combined with the enhanced expression of inflammatory mediators that are induced by chronic alcohol, a proinflammatory state develops within WAT, contributing to the observed lipodystrophy. Lastly, while chronic alcohol intake may enhance thermogenesis of brown adipose tissue (BAT, definitive mechanistic evidence is currently lacking. Overall, both WAT and BAT depots are impacted by chronic alcohol intake and the resulting lipodystrophy contributes to fat accumulation in peripheral organs, thereby enhancing the pathological state accompanying chronic alcohol use disorder.

Evaluating childhood obesity. Magnetic resonance-based quantification of abdominal adipose tissue and liver fat in children

International Nuclear Information System (INIS)

Raschpichler, M.C.; Leipzig Univ. Medical Center; Sorge, I.; Hirsch, W.; Mende, M.; Sergeyev, E.; Koerner, A.; Kruber, D.; Schick, F.

2012-01-01

The purpose of this study is to establish and validate a magnetic resonance (MR)-based fat quantification package that provides an accurate assessment of abdominal adipose tissue and liver fat in children. Ex vivo trials with a torso model and water-oil mixtures are conducted. Abdominal adipose tissue (AAT) is covered by magnetic resonance imaging (MRI) using a fat-selective sequence and is analyzed by a plug-in based on the open source software Image. Liver fat (LF) is measured with localized 1 H Magnetic Resonance Spectroscopy ( 1 H MRS) and the jMRUI (java-based Magnetic Resonance User Interface) software package. Evaluation of the clinical methodology involved a study of 10 children in this feasibility study (mean age and body mass index: 13.3 yr; 33.3 kg/m 2 ). To evaluate the method's validity, reference measurements were performed. Ex vivo trials with the torso model showed that adipose tissue was measured appropriately with a systematic underestimation by 9.3 ± 0.2 % (0.32 ± 0.064 kg). Coefficients of variation for both intra- and inter-observer measurements ranged between 0 - 2.7 % and repeated analyses showed significant equivalent results (p 1 H MRS ex vivo revealed significant equivalence with the predefined fat content in water-oil mixtures (p < 0.01). In vivo, the homemade plug-in significantly overestimated the AAT, with the visceral adipose tissue being most affected (+ 15.7 ± 8.4 %). Although an overestimation of the AAT by the presented plug-in should be taken into consideration, this children-friendly package enables the quantification of both LF and AAT within 30 min on a freeware-based platform. (orig.)

Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis.

Science.gov (United States)

Choi, Youngshim; Abdelmegeed, Mohamed A; Song, Byoung-Joon

2018-05-01

Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to evaluate the preventive effects of I3C against ethanol (EtOH)-induced liver injury and study the protective mechanism(s) by using the well-established chronic-plus-binge alcohol exposure model. The preventive effects of I3C were evaluated by conducting various histological, biochemical, and real-time PCR analyses in mouse liver, adipose tissue, and colon, since functional alterations of adipose tissue and intestine can also participate in promoting EtOH-induced liver damage. Daily treatment with I3C alleviated EtOH-induced liver injury and hepatocyte apoptosis, but not steatosis, by attenuating elevated oxidative stress, as evidenced by the decreased levels of hepatic lipid peroxidation, hydrogen peroxide, CYP2E1, NADPH-oxidase, and protein acetylation with maintenance of mitochondrial complex I, II, and III protein levels and activities. I3C also restored the hepatic antioxidant capacity by preventing EtOH-induced suppression of glutathione contents and mitochondrial aldehyde dehydrogenase-2 activity. I3C preventive effects were also achieved by attenuating the increased levels of hepatic proinflammatory cytokines, including IL1β, and neutrophil infiltration. I3C also attenuated EtOH-induced gut leakiness with decreased serum endotoxin levels through preventing EtOH-induced oxidative stress, apoptosis of enterocytes, and alteration of tight junction protein claudin-1. Furthermore, I3C alleviated adipose tissue inflammation and decreased free fatty acid release. Collectively, I3C prevented EtOH-induced liver injury via attenuating the damaging effect of ethanol on the gut-liver-adipose tissue axis. Therefore, I3C may also have a high potential for translational research in treating or preventing other types of hepatic injury associated with oxidative stress and inflammation. Copyright © 2017 Elsevier Inc. All

Lipasin/betatrophin is differentially expressed in liver and white adipose tissue without association with insulin resistance in Wistar and Goto-Kakizaki rats.

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Cahová, M; Habart, D; Olejár, T; Berková, Z; Papáčková, Z; Daňková, H; Lodererova, A; Heczková, M; Saudek, F

2017-05-04

Lipasin is a recently identified lipokine expressed predominantly in liver and in adipose tissue. It was linked to insulin resistance in mice and to type 1 and type 2 diabetes (T1D, T2D) in humans. No metabolic studies concerning lipasin were performed yet in rats. Therefore, we used rat model of T2D and insulin resistance, Goto-Kakizaki (GK) rats, to determine changes of lipasin expression in liver and in white adipose tissue (WAT) over 52 weeks in the relation to glucose tolerance, peripheral tissue insulin sensitivity and adiposity. GK rats were grossly glucose intolerant since the age of 6 weeks and developed peripheral insulin resistance at the age of 20 weeks. Expression of lipasin in the liver did not differ between GK and Wistar rats, declining with age, and it was not related to hepatic triacylglycerol content. In WAT, the lipasin expression was significantly higher in Wistar rats where it correlated positively with adiposity. No such correlation was found in GK rats. In conclusion, lipasin expression was associated neither with a mild age-related insulin resistance (Wistar), nor with severe genetically-based insulin resistance (GK).

Evaluating childhood obesity. Magnetic resonance-based quantification of abdominal adipose tissue and liver fat in children

Energy Technology Data Exchange (ETDEWEB)

Raschpichler, M.C. [Leipzig Univ. (Germany). Dept. of Paediatric Radiology; Leipzig Univ. Medical Center (Germany). IFB Adiposity Diseases; Sorge, I.; Hirsch, W. [Leipzig Univ. (Germany). Dept. of Paediatric Radiology; Mende, M. [Leipzig Univ. (Germany). Clinical Trial Centre Leipzig; Sergeyev, E.; Koerner, A. [Leipzig Univ. (Germany). University Hospital for Children and Adolescents; Kruber, D. [Leipzig Univ. (Germany). Dept. of Oral, Craniomaxillofacial and Facial Plastic Surgery; Schick, F. [Univ. Hospital Tuebingen (Germany). Section on Experimental Radiology

2012-04-15

The purpose of this study is to establish and validate a magnetic resonance (MR)-based fat quantification package that provides an accurate assessment of abdominal adipose tissue and liver fat in children. Ex vivo trials with a torso model and water-oil mixtures are conducted. Abdominal adipose tissue (AAT) is covered by magnetic resonance imaging (MRI) using a fat-selective sequence and is analyzed by a plug-in based on the open source software Image. Liver fat (LF) is measured with localized {sup 1}H Magnetic Resonance Spectroscopy ({sup 1}H MRS) and the jMRUI (java-based Magnetic Resonance User Interface) software package. Evaluation of the clinical methodology involved a study of 10 children in this feasibility study (mean age and body mass index: 13.3 yr; 33.3 kg/m{sup 2}). To evaluate the method's validity, reference measurements were performed. Ex vivo trials with the torso model showed that adipose tissue was measured appropriately with a systematic underestimation by 9.3 {+-} 0.2 % (0.32 {+-} 0.064 kg). Coefficients of variation for both intra- and inter-observer measurements ranged between 0 - 2.7 % and repeated analyses showed significant equivalent results (p < 0.01). The lipid content obtained by {sup 1}H MRS ex vivo revealed significant equivalence with the predefined fat content in water-oil mixtures (p < 0.01). In vivo, the homemade plug-in significantly overestimated the AAT, with the visceral adipose tissue being most affected (+ 15.7 {+-} 8.4 %). Although an overestimation of the AAT by the presented plug-in should be taken into consideration, this children-friendly package enables the quantification of both LF and AAT within 30 min on a freeware-based platform. (orig.)

Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

International Nuclear Information System (INIS)

Chen, Qi-Liang; Luo, Zhi; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

2013-01-01

Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

Energy Technology Data Exchange (ETDEWEB)

Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

2013-07-15

Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.

Directory of Open Access Journals (Sweden)

Ori Nov

Full Text Available The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers, Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4 that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin

Proteomic Profiles of Adipose and Liver Tissues from an Animal Model of Metabolic Syndrome Fed Purple Vegetables

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Hala M Ayoub

2018-04-01

Full Text Available Metabolic Syndrome (MetS is a complex disorder that predisposes an individual to Cardiovascular Diseases and type 2 Diabetes Mellitus. Proteomics and bioinformatics have proven to be an effective tool to study complex diseases and mechanisms of action of nutrients. We previously showed that substitution of the majority of carbohydrate in a high fat diet by purple potatoes (PP or purple carrots (PC improved insulin sensitivity and hypertension in an animal model of MetS (obese Zucker rats compared to a control sucrose-rich diet. In the current study, we used TMT 10plex mass tag combined with LC-MS/MS technique to study proteomic modulation in the liver (n = 3 samples/diet and adipose tissue (n = 3 samples/diet of high fat diet-fed rats with or without substituting sucrose for purple vegetables, followed by functional enrichment analysis, in an attempt to elucidate potential molecular mechanisms responsible for the phenotypic changes seen with purple vegetable feeding. Protein folding, lipid metabolism and cholesterol efflux were identified as the main modulated biological themes in adipose tissue, whereas lipid metabolism, carbohydrate metabolism and oxidative stress were the main modulated themes in liver. We propose that enhanced protein folding, increased cholesterol efflux and higher free fatty acid (FFA re-esterification are mechanisms by which PP and PC positively modulate MetS pathologies in adipose tissue, whereas, decreased de novo lipogenesis, oxidative stress and FFA uptake, are responsible for the beneficial effects in liver. In conclusion, we provide molecular evidence for the reported metabolic health benefits of purple carrots and potatoes and validate that these vegetables are good choices to replace other simple carbohydrate sources for better metabolic health.

Cloning Changes the Response to Obesity of Innate Immune Factors in Blood, Liver, and Adipose Tissues in Domestic Pigs

DEFF Research Database (Denmark)

Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Stagsted, Jan

2013-01-01

The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune...... factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both...... upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls...

Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

Science.gov (United States)

Rodrigues, Angélica Heringer; Moreira, Carolina Campos Lima; Neves, Maria José; Botion, Leida Maria; Chaves, Valéria Ernestânia

2018-06-01

Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets. Copyright © 2018. Published by Elsevier Inc.

A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity-induced inflammation in white adipose tissue and liver.

Science.gov (United States)

Gotoh, Koro; Inoue, Megumi; Masaki, Takayuki; Chiba, Seiichi; Shimasaki, Takanobu; Ando, Hisae; Fujiwara, Kansuke; Katsuragi, Isao; Kakuma, Tetsuya; Seike, Masataka; Sakata, Toshiie; Yoshimatsu, Hironobu

2012-08-01

Obesity is associated with systemic low-grade inflammation and obesity-related metabolic disorders. Considering that obesity decreases the expression of proinflammatory cytokines in the spleen, we assessed the role of interleukin (IL)-10, an anti-inflammatory cytokine produced by the spleen, in the pathogenesis of obesity. Changes in obesity-related pathogenesis, including inflammatory responses in multiple organs, were assessed after systemic administration of exogenous IL-10 to splenectomy (SPX)-treated obese wild-type and IL-10 knockout (IL-10KO) mice. Obesity resulted in the inability of the spleen to synthesize cytokines, including IL-10, and proinflammatory cytokines in obesity are then likely to emerge from tissues other than the spleen because serum levels of IL-10, but not proinflammatory cytokines, decreased despite the expression of these cytokines in the spleen being reduced in high fat-induced obese mice. SPX aggravated the inflammatory response in white adipose tissue (WAT) and the liver and suppressed adiposity in WAT. However, it accentuated adiposity in the liver. These SPX-induced changes were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on the inflammatory responses in WAT and the liver of IL-10KO mice. These data show the role of spleen-derived IL-10 in diet-induced changes as a result of inflammatory responses in WAT and the liver.

Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss.

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Schmitz, J; Evers, N; Awazawa, M; Nicholls, H T; Brönneke, H S; Dietrich, A; Mauer, J; Blüher, M; Brüning, J C

2016-05-01

Obesity represents a major risk factor for the development of type 2 diabetes mellitus, atherosclerosis and certain cancer entities. Treatment of obesity is hindered by the long-term maintenance of initially reduced body weight, and it remains unclear whether all pathologies associated with obesity are fully reversible even upon successfully maintained weight loss. We compared high fat diet-fed, weight reduced and lean mice in terms of body weight development, adipose tissue and liver insulin sensitivity as well as inflammatory gene expression. Moreover, we assessed similar parameters in a human cohort before and after bariatric surgery. Compared to lean animals, mice that demonstrated successful weight reduction showed increased weight gain following exposure to ad libitum control diet. However, pair-feeding weight-reduced mice with lean controls efficiently stabilized body weight, indicating that hyperphagia was the predominant cause for the observed weight regain. Additionally, whereas glucose tolerance improved rapidly after weight loss, systemic insulin resistance was retained and ameliorated only upon prolonged pair-feeding. Weight loss enhanced insulin action and resolved pro-inflammatory gene expression exclusively in the liver, whereas visceral adipose tissue displayed no significant improvement of metabolic and inflammatory parameters compared to obese mice. Similarly, bariatric surgery in humans (n = 55) resulted in massive weight reduction, improved hepatic inflammation and systemic glucose homeostasis, while adipose tissue inflammation remained unaffected and adipocyte-autonomous insulin action only exhibit minor improvements in a subgroup of patients (42%). These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as

Toward angiogenesis of implanted bio-artificial liver using scaffolds with type I collagen and adipose tissue-derived stem cells.

Science.gov (United States)

Lee, Jae Geun; Bak, Seon Young; Nahm, Ji Hae; Lee, Sang Woo; Min, Seon Ok; Kim, Kyung Sik

2015-05-01

Stem cell therapies for liver disease are being studied by many researchers worldwide, but scientific evidence to demonstrate the endocrinologic effects of implanted cells is insufficient, and it is unknown whether implanted cells can function as liver cells. Achieving angiogenesis, arguably the most important characteristic of the liver, is known to be quite difficult, and no practical attempts have been made to achieve this outcome. We carried out this study to observe the possibility of angiogenesis of implanted bio-artificial liver using scaffolds. This study used adipose tissue-derived stem cells that were collected from adult patients with liver diseases with conditions similar to the liver parenchyma. Specifically, microfilaments were used to create an artificial membrane and maintain the structure of an artificial organ. After scratching the stomach surface of severe combined immunocompromised (SCID) mice (n=4), artificial scaffolds with adipose tissue-derived stem cells and type I collagen were implanted. Expression levels of angiogenesis markers including vascular endothelial growth factor (VEGF), CD34, and CD105 were immunohistochemically assessed after 30 days. Grossly, the artificial scaffolds showed adhesion to the stomach and surrounding organs; however, there was no evidence of angiogenesis within the scaffolds; and VEGF, CD34, and CD105 expressions were not detected after 30 days. Although implantation of cells into artificial scaffolds did not facilitate angiogenesis, the artificial scaffolds made with type I collagen helped maintain implanted cells, and surrounding tissue reactions were rare. Our findings indicate that type I collagen artificial scaffolds can be considered as a possible implantable biomaterial.

Chronic alcohol exposure disturbs lipid homeostasis at the adipose tissue-liver axis in mice: analysis of triacylglycerols using high-resolution mass spectrometry in combination with in vivo metabolite deuterium labeling.

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Xiaoli Wei

Full Text Available A method of employing high-resolution mass spectrometry in combination with in vivo metabolite deuterium labeling was developed in this study to investigate the effects of alcohol exposure on lipid homeostasis at the white adipose tissue (WAT-liver axis in a mouse model of alcoholic fatty liver. In order to differentiate the liver lipids synthesized from the fatty acids that were transported back from adipose tissue and the lipids synthesized from other sources of fatty acids, a two-stage mouse feeding experiment was performed to incorporate deuterium into metabolites. Hepatic lipids extracted from mouse liver, epididymal white adipose tissue (eWAT and subcutaneous white adipose tissue (sWAT were analyzed. It was found that 13 and 10 triacylglycerols (TGs incorporated with a certain number of deuterium were significantly increased in alcohol induced fatty liver at two and four weeks of alcohol feeding periods, respectively. The concentration changes of these TGs ranged from 1.7 to 6.3-fold increase. A total of 14 deuterated TGs were significantly decreased in both eWAT and sWAT at the two and four weeks and the fold-change ranged from 0.19 to 0.77. The increase of deuterium incorporated TGs in alcohol-induced fatty liver and their decrease in both eWAT and sWAT indicate that alcohol exposure induces hepatic influx of fatty acids which are released from WATs. The results of time course analysis further indicate a mechanistic link between adipose fat loss and hepatic fat gain in alcoholic fatty liver.

Maternal high-fat diet modulates brown adipose tissue response to B-adrenergic agonist

Science.gov (United States)

Maternal obesity increases offspring risk for several metabolic diseases. We previously showed that offspring of obese dams are predisposed to obesity, liver and adipose tissue anomalies. However, the effect of maternal obesity on developmental programing brown adipose tissue (BAT) is poorly underst...

Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57Bl/6 mice

NARCIS (Netherlands)

Duval, C.; Thissen, U.; Keshtkar, S.; Accart, B.; Stienstra, R.; Boekschoten, M.V.; Roskams, T.; Kersten, S.; Müller, M.

2010-01-01

OBJECTIVE - Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here, we aimed to investigate the interaction between adipose tissue and liver in NAFLD and identify potential early plasma markers

Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57BL/6 mice.

NARCIS (Netherlands)

Duval, C.; Thissen, U.; Keshtkar, S.; Accart, B.; Stienstra, R.; Boekschoten, M.V.; Roskams, T.; Kersten, S.; Muller, M.

2010-01-01

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here, we aimed to investigate the interaction between adipose tissue and liver in NAFLD and identify potential early plasma markers that

Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57Bl/6 mice

NARCIS (Netherlands)

Duval, C.N.C.; Thissen, Uwe; Keshtkar, Shohreh; Accard, Bertrand; Stienstra, Rinke; Boekschoten, Mark; Roskams, Tania; Kersten, Sander; Muller, Michael

2010-01-01

Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that

Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57BL/6 mice

NARCIS (Netherlands)

Duval, C.N.C.; Thissen, U.; Keshtkar, S.; Accart, B.; Stienstra, R.; Boekschoten, M.V.; Roskams, T.; Kersten, A.H.; Müller, M.R.

2010-01-01

Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that

Lipid composition of hepatic and adipose tissues from normal cats and from cats with idiopathic hepatic lipidosis.

Science.gov (United States)

Hall, J A; Barstad, L A; Connor, W E

1997-01-01

The purpose of this study was to characterize the lipid classes in hepatic and adipose tissues from cats with idiopathic hepatic lipidosis (IHL). Concentrations of triglyceride, phospholipid phosphorus, and free and total cholesterol were determined in lipid extracts of liver homogenates from 5 cats with IHL and 5 healthy control cats. Total fatty acid composition of liver and adipose tissue was also compared. Triglyceride accounted for 34% of liver by weight in cats with IHL (338 +/- 38 mg/g wet liver) versus 1% in control cats (9.9 +/- 1.0 mg/g wet liver, P hepatic tissue in the 2 groups differed; palmitate was higher (19.5 +/- 1.1% of total fatty acids in cats with IHL versus 9.2 +/- 2.7% in controls, P hepatic triglyceride in cats with IHL is the mobilization of fatty acids from adipose tissue.

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Science.gov (United States)

Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

2015-01-01

Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia – before severe fat loss – in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34–42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition. PMID:25457061

Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

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J. Schmitz

2016-05-01

Conclusions: These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as well as in a significant subpopulation of obese patients.

Ethnic influences on the relations between abdominal subcutaneous and visceral adiposity, liver fat, and cardiometabolic risk profile: the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity.

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Nazare, Julie-Anne; Smith, Jessica D; Borel, Anne-Laure; Haffner, Steven M; Balkau, Beverley; Ross, Robert; Massien, Christine; Alméras, Natalie; Després, Jean-Pierre

2012-10-01

Ethnic differences in cardiometabolic risk (CMR) may be related to patterns of ethnic-specific body fat distribution. We aimed to identify differences across ethnic groups in interrelations between BMI, abdominal adiposity, liver fat, and CMR profile. In the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity, 297 physicians recruited 4504 patients (from 29 countries). In the current cross-sectional analyses, 2011 whites, 166 African Caribbean blacks, 381 Hispanics, 1192 East Asians, and 347 Southeast Asians were included. Computed tomography was used to assess abdominal fat distribution and to estimate liver fat content. Anthropometric variables and CMR profile were measured. Higher ranges of BMI were associated with higher levels of visceral [visceral adipose tissue (VAT)] and deep subcutaneous [deep subcutaneous adipose tissue (DSAT)] adiposity, with significant ethnic differences regarding the slope of these relations. Despite lower absolute BMI values, East Asians presented the largest accumulation of VAT but the lowest accumulation of DSAT with increasing adiposity. The association of BMI with liver fat did not differ between ethnic groups. Liver fat and DSAT were positively correlated with VAT with no ethnic variation. All ethnic groups had a similar association between a 1-SD increase in VAT, DSAT, or liver fat with hypertension, type 2 diabetes, hypertriglyceridemia, low HDL-cholesterol concentration, or high C-reactive protein concentration. Ethnicity significantly affects abdominal adiposity and liver fat partitioning, and East Asians have the most deleterious abdominal fat distribution. Irrespective of ethnicity, abdominal and hepatic fat depots are strongly interrelated and increased with obesity. Higher amounts of VAT or liver fat are associated with a more deteriorated CMR profile in all ethnic groups.

Effects of a Diet Enriched with Polyunsaturated, Saturated, or Trans Fatty Acids on Cytokine Content in the Liver, White Adipose Tissue, and Skeletal Muscle of Adult Mice

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Bruno dos Santos

2013-01-01

Full Text Available This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet; soybean oil (S; lard (L; and hydrogenated vegetable fat (H. We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver.

Sexual dimorphism in hepatic, adipose tissue and peripheral tissue insulin sensitivity in obese humans

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Kasper W. ter Horst

2015-11-01

Full Text Available Glucose and lipid metabolism differ between men and women, and women tend to have better whole-body or muscle insulin sensitivity. This may be explained, in part, by differences in sex hormones and adipose tissue distribution. Few studies have investigated gender differences in hepatic, adipose tissue and whole-body insulin sensitivity between severely obese men and women. In this study, we aimed to determine the differences in glucose metabolism between severely obese men and women using tissue-specific measurements of insulin sensitivity. Insulin sensitivity was compared between age and body mass index (BMI-matched obese men and women by a two-step euglycemic hyperinsulinemic clamp with infusion of [6,6-2H2]glucose. Basal endogenous glucose production and insulin sensitivity of the liver, adipose tissue and peripheral tissues were assessed. Liver fat content was assessed by proton magnetic resonance spectroscopy in a subset of included subjects. We included 46 obese men and women (age, 48±2 vs 46±2 years, p=0.591; BMI, 41±1 vs 41±1 kg/m2, p=0.832. There was no difference in basal endogenous glucose production (14.4±1.0 vs 15.3±0.5 µmol•kg fat-free mass-1•min-1, p=0.410, adipose tissue insulin sensitivity (insulin-mediated suppression of free fatty acids, 71.6±3.6 vs 76.1±2.6%, p=0.314 or peripheral insulin sensitivity (insulin-stimulated rate of disappearance of glucose, 26.2±2.1 vs 22.7±1.7 µmol•kg-1•min-1, p=0.211. Obese men were characterized by lower hepatic insulin sensitivity (insulin-mediated suppression of endogenous glucose production, 61.7±4.1 vs 72.8±2.5% in men vs women, resp., p=0.028. Finally, these observations could not be explained by differences in liver fat content (men vs women, 16.5±3.1 vs 16.0±2.5%, p=0.913, n=27.We conclude that obese men have lower hepatic, but comparable adipose tissue and peripheral tissue, insulin sensitivity compared to similarly obese women. Hepatic insulin resistance may

Gene Expression Signature in Adipose Tissue of Acromegaly Patients

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Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave

2015-01-01

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292

Orosomucoid expression profiles in liver, adipose tissues and serum of lean and obese domestic pigs, Göttingen minipigs and Ossabaw minipigs.

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Rødgaard, Tina; Stagsted, Jan; Christoffersen, Berit Ø; Cirera, Susanna; Moesgaard, Sophia G; Sturek, Michael; Alloosh, Mouhamad; Heegaard, Peter M H

2013-02-15

The acute phase protein orosomucoid (ORM) has anti-inflammatory and immunomodulatory effects, and may play an important role in the maintenance of metabolic homeostasis in obesity-induced low-grade inflammation. Even though the pig is a widely used model for obesity related metabolic symptoms, the expression of ORM has not yet been characterized in such pig models. The objective of this study was to investigate the expression of ORM1 mRNA in liver, visceral adipose tissue, subcutaneous adipose tissue (SAT) from the abdomen or retroperitoneal abdominal adipose tissue (RPAT) and SAT from the neck, as well as the serum concentration of ORM protein in three porcine obesity models; the domestic pig, Göttingen minipigs and Ossabaw minipigs. No changes in ORM1 mRNA expression were observed in obese pigs compared to lean pigs in the four types of tissues. However, obese Ossabaw minipigs, but none of the other breeds, showed significantly elevated ORM serum concentrations compared to their lean counterparts. Studies in humans have shown that the expression of ORM was unchanged in adipose tissue depots in obese humans with an increased serum concentration of ORM. Thus in this respect, obese Ossabaw minipigs behave more similarly to obese humans than the other two pig breeds investigated. Copyright © 2012 Elsevier B.V. All rights reserved.

Protein Kinase A Regulatory Subunits in Human Adipose Tissue

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Mantovani, Giovanna; Bondioni, Sara; Alberti, Luisella; Gilardini, Luisa; Invitti, Cecilia; Corbetta, Sabrina; Zappa, Marco A.; Ferrero, Stefano; Lania, Andrea G.; Bosari, Silvano; Beck-Peccoz, Paolo; Spada, Anna

2009-01-01

OBJECTIVE—In human adipocytes, the cAMP-dependent pathway mediates signals originating from β-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e., lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B regulatory isoform is the most expressed in mouse adipose tissue, where it protects against diet-induced obesity and fatty liver development. The aim of the study was to investigate possible differences in R2B expression, PKA activity, and lipolysis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS—The expression of the different PKA regulatory subunits was evaluated by immunohistochemistry, Western blot, and real-time PCR in subcutaneous and visceral adipose tissue samples from 20 nonobese and 67 obese patients. PKA activity and glycerol release were evaluated in total protein extract and adipocytes isolated from fresh tissue samples, respectively. RESULTS—Expression techniques showed that R2B was the most abundant regulatory protein, both at mRNA and protein level. Interestingly, R2B mRNA levels were significantly lower in both subcutaneous and visceral adipose tissues from obese than nonobese patients and negatively correlated with BMI, waist circumference, insulin levels, and homeostasis model assessment of insulin resistance. Moreover, both basal and stimulated PKA activity and glycerol release were significantly lower in visceral adipose tissue from obese patients then nonobese subjects. CONCLUSIONS—Our results first indicate that, in human adipose tissue, there are important BMI-related differences in R2B expression and PKA activation, which might be included among the multiple determinants involved in the different lipolytic response to β-adrenergic activation in obesity. PMID:19095761

Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

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Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

2016-01-01

Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone–fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues – subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT – is differently associated wi...

FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression regarding circulating plasma levels.

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María Isabel Queipo-Ortuño

Full Text Available BACKGROUND: FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. OBJECTIVE: In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. METHODS: The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. RESULTS: In obesity FABP4 expression was down-regulated (at both mRNA and protein levels, with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. CONCLUSION: The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity.

Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury

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Eva Koellensperger

2013-01-01

Full Text Available In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20. Injection of cell culture medium performed in group 2 (n = 20 served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017, total protein (P < 0.031, glutamic oxaloacetic transaminase (P < 0.001, and lactate dehydrogenase (P < 0.04 levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

Effects of adrenal hormones on the expression of adiponectin and adiponectin receptors in adipose tissue, muscle and liver.

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de Oliveira, Cristiane; Iwanaga-Carvalho, Carla; Mota, João F; Oyama, Lila M; Ribeiro, Eliane B; Oller do Nascimento, Cláudia M

2011-11-01

Adiponectin, an insulin-sensitive hormone that is primarily synthesized in adipose tissue, exerts its effects by binding to two receptors, adipoR1 and adipoR2. Little is known regarding the effects of glucocorticoids on the expression of adiponectin receptors. Male Wistar rats were bilaterally adrenalectomized and treated with dexamethasone (0.2 mg/100 g) twice daily for 3 days. To analyze the potential effects of glucocorticoids, rats received two daily injections of the glucocorticoid receptor antagonist (RU-486, 5.0 mg) over the course of 3 days. Additionally, 3T3-L1 adipocytes and C2C12 myotubes were treated with dexamethasone, adrenaline or RU-486. The gene expression of adiponectin, adipoR1 and adipoR2 was determined by real-time PCR, and protein secretion was examined by Western blotting using lysates from retroperitoneal, epididymal and subcutaneous adipose tissue depots, liver and muscle. In rats, excess glucocorticoids increased the levels of insulin in serum and decreased serum adiponectin concentrations, whereas adrenalectomy decreased the mRNA expression of adiponectin (3-fold) and adipoR2 (7-fold) in epididymal adipose tissue and increased adipoR2 gene expression in muscle (3-fold) compared to control group sham-operated. Dexamethasone treatment did not reverse the effects of adrenalectomy, and glucocorticoid receptor blockade did not reproduce the effects of adrenalectomy. In 3T3-L1 adipocytes, dexamethasone and adrenaline both increased adipoR2 mRNA levels, but RU-486 reduced adipoR2 gene expression in vitro. Dexamethasone treatment induces a state of insulin resistance but does not affect adiponectin receptor expression in adipose tissue. However, the effects of catecholamines on insulin resistance may be due to their effects on adipoR2. Copyright © 2011 Elsevier Inc. All rights reserved.

Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.

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Tanaka, Mitsuru; Yasuoka, Akihito; Shimizu, Manae; Saito, Yoshikazu; Kumakura, Kei; Asakura, Tomiko; Nagai, Toshitada

2017-01-01

To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H) containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45 in energy percent, respectively). The rats consumed the diets for 9 weeks and were subjected to biochemical and DNA microarray analyses. The rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher liver TG and cholesterol content than rats in the L-group. The analysis of differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene ontology analysis of these L vs H DEGs indicated that those related to fatty acid synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These reversed liver DEGs included M-up/H-down genes ( Sds for gluconeogenesis from amino acids) and M-down/H-up genes ( Gpd2 for gluconeogenesis from glycerol, Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation and synthesis of fatty acids were inhibited in these tissues. These results indicate that the alteration of dietary C-F balance differentially affects the transcriptomes of metabolizing and energy-storing tissues.

Distribution of abdominal adipose tissue as a predictor of hepatic steatosis assessed by MRI

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Ducluzeau, P.-H.; Manchec-Poilblanc, P.; Roullier, V.; Cesbron, E.; Lebigot, J.; Bertrais, S.; Aube, C.

2010-01-01

Aim: To evaluate the relationship between the distribution of visceral and subcutaneous adipose tissue and hepatic steatosis assessed using magnetic resonance imaging (MRI). Materials and methods: One T1-weighted, in-/out-of-phase, single-section sequence at the L3/L4 level and one multi-echo gradient MRI (MGRE) sequence were performed on 65 patients [19 females and 46 males; age 57 ± 9.5 years; body mass index (BMI) 31 ± 5.1 kg/m 2 ]. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) surfaces, and hepatic steatosis were automatically calculated using in-house software. Weight, height, BMI, waist circumference, hip circumference, and waist:hip ratio were recorded. The probability of having a steatosis greater than 10% on MRI was evaluated by receiver operating characteristic (ROC) curves. Results: The anthropometric parameter best correlated to hepatic steatosis was the waist-to-hip ratio (r = 0.301). VAT and proportion of VAT were correlated to liver fat content (r = 0.307 and r = 0.249, respectively). No significant correlations were found for BMI, hip circumference, and SAT. The area under the receiver operating characteristics (AUROCs) for the relationship between liver steatosis and BMI, waist circumference, waist:hip ratio, VAT surface, and proportion of VAT, were respectively 0.52, 0.63, 0.71, 0.73 and 0.75. Conclusion: Adipose tissue distribution is more relevant than total fat mass when assessing the possibility of liver steatosis in overweight patients.

Distribution of abdominal adipose tissue as a predictor of hepatic steatosis assessed by MRI

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Ducluzeau, P.-H. [Department of endocrinology-Diabetology-Nutrition, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Manchec-Poilblanc, P., E-mail: Manchecp@yahoo.f [Department of Radiology, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Roullier, V. [Department of Radiology, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); LISA, Laboratoire d' Ingenierie des Systemes Automatises, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Cesbron, E. [Department of digestive and liver disease, Universitary hospital of Angers, Faculty of Medicine of Angers (France); Lebigot, J. [Department of Radiology, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Bertrais, S. [HIFIH Laboratory, UPRES EA 3859, IFR 132, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Aube, C. [Department of Radiology, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); HIFIH Laboratory, UPRES EA 3859, IFR 132, Universitary Hospital of Angers, Faculty of Medicine of Angers (France)

2010-09-15

Aim: To evaluate the relationship between the distribution of visceral and subcutaneous adipose tissue and hepatic steatosis assessed using magnetic resonance imaging (MRI). Materials and methods: One T1-weighted, in-/out-of-phase, single-section sequence at the L3/L4 level and one multi-echo gradient MRI (MGRE) sequence were performed on 65 patients [19 females and 46 males; age 57 {+-} 9.5 years; body mass index (BMI) 31 {+-} 5.1 kg/m{sup 2}]. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) surfaces, and hepatic steatosis were automatically calculated using in-house software. Weight, height, BMI, waist circumference, hip circumference, and waist:hip ratio were recorded. The probability of having a steatosis greater than 10% on MRI was evaluated by receiver operating characteristic (ROC) curves. Results: The anthropometric parameter best correlated to hepatic steatosis was the waist-to-hip ratio (r = 0.301). VAT and proportion of VAT were correlated to liver fat content (r = 0.307 and r = 0.249, respectively). No significant correlations were found for BMI, hip circumference, and SAT. The area under the receiver operating characteristics (AUROCs) for the relationship between liver steatosis and BMI, waist circumference, waist:hip ratio, VAT surface, and proportion of VAT, were respectively 0.52, 0.63, 0.71, 0.73 and 0.75. Conclusion: Adipose tissue distribution is more relevant than total fat mass when assessing the possibility of liver steatosis in overweight patients.

Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise

DEFF Research Database (Denmark)

Frydelund-Larsen, Lone; Åkerström, Thorbjörn; Nielsen, Søren

2006-01-01

in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of Vo(2 max) or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4......Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression.......5, and 6 h in response to exercise (n = 8) compared with preexercise samples and compared with the resting control group (n = 7, P = 0.001). Visfatin mRNA expression in skeletal muscle was not influenced by exercise. The exercise-induced increase in adipose tissue visfatin was, however, not accompanied...

Epicardial Adipose Tissue (EAT Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease.

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Anna Ludovica Fracanzani

Full Text Available Epicardial adipose tissue (EAT has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD. Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1 the association between EAT, the other metabolic parameters and the severity of steatosis 2 the relationship between cardiovascular (cIMT, cplaques, E/A, liver (presence of NASH and significant fibrosis damage and metabolic risk factors including EAT 3 the relationship between EAT and genetic factors strongly influencing liver steatosis.In a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100. EAT, severity of steatosis, carotid intima-media thickness (cIMT and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm were female gender (p = 0.003, age (p = 0.001, BMI (p = 0.01, diastolic blood pressure (p = 0.009, steatosis grade 2 (p = 0.01 and 3 (p = 0.04, fatty liver index (p = 0.001 and statin use (p = 0.03. Variables independently associated with carotid IMT were age (p = 0.0001, hypertension (p = 0.009, diabetes (p = 0.04, smoking habits (p = 0.04 and fatty liver index (p = 0.02, with carotid plaques age (p = 0.0001, BMI (p = 0.03, EAT (p = 0.02, and hypertension (p = 0.02, and with E/A age (p = 0.0001, diabetes (p = 0.005, hypertension (p = 0.04 and fatty liver index (p = 0.004. In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH was independently associated with EAT (p = 0.04 and diabetes (p = 0.054 while significant fibrosis with EAT (p = 0.02, diabetes (p = 0.01 and waist circumference (p = 0.05. No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found.In patients with NAFLD, EAT is associated with the severity of liver and vascular damage besides with the known metabolic risk factors.

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*

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Huo, Yuqing; Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Fan, Yang-Yi; Ong, Kuok Teong; Woo, Shih-Lung; Chapkin, Robert S.; Mashek, Douglas G.; Chen, Yanming; Dong, Hui; Lu, Fuer; Wei, Lai; Wu, Chaodong

2012-01-01

Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. PMID:22556414

Irbesartan increased PPARγ activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

International Nuclear Information System (INIS)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

2011-01-01

Research highlights: → Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. → Irbesartan decreased white adipose tissue weight without affecting body weight. → DNA-binding for PPARγ was increased in white adipose tissue in vivo by irbesartan. → Irbesartan increased adipocyte number in white adipose tissue. → Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPARγ agonistic action of an AT 1 receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPARγ in white adipose tissue and the DNA-binding activity of PPARγ in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPARγ and improved adipose tissue dysfunction including insulin resistance.

Excessive Endoplasmic Reticulum Stress Correlates with Impaired Mitochondrial Dynamics, Mitophagy and Apoptosis, in Liver and Adipose Tissue, but Not in Muscles in EMS Horses

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Krzysztof Marycz

2018-01-01

Full Text Available Nowadays, endocrine disorders have become more frequent in both human and veterinary medicine. In horses, reduced physical activity combined with carbohydrate and sugar overload may result in the development of the so-called equine metabolic syndrome (EMS. EMS is characterized by insulin resistance, hyperinsulinemia, elevated blood triglyceride concentrations and usually obesity. Although the phenotypic features of EMS individuals are well known, the molecular mechanism underlying disease development remains elusive. Therefore, in the present study, we analyzed insulin-sensitive tissues, i.e., muscles, liver and adipose tissue in order to evaluate insulin resistance and apoptosis. Furthermore, we assessed mitochondrial dynamics and mitophagy in those tissues, because mitochondrial dysfunction is linked to the development of metabolic syndrome. We established the expression of genes related to insulin resistance, endoplasmic reticulum (ER stress and mitochondria clearance by mitophagy using RT-PCR and Western blot. Cell ultrastructure was visualized using electron transmission microscopy. The results indicated that adipose tissue and liver of EMS horses were characterized by increased mitochondrial damage and mitophagy followed by triggering of apoptosis as mitophagy fails to restore cellular homeostasis. However, in muscles, apoptosis was reduced, suggesting the existence of a protective mechanism allowing that tissue to maintain homeostasis.

Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

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Jialin Xu

Full Text Available AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD, regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting. METHODS AND RESULTS: Male C57BL/6 (WT and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36 and Fatty acid transport protein (FATP 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation.

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Bjørndal, Bodil; Berge, Christ; Ramsvik, Marie Sannes; Svardal, Asbjørn; Bohov, Pavol; Skorve, Jon; Berge, Rolf K

2013-10-07

There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNFα). hTNFα mice (C57BL/6 hTNFα) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ∆6 and ∆9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-γ level was observed. Plasma carnitine and the carnitine precursor γ-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal β-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.

Fat body, fat pad and adipose tissues in invertebrates and vertebrates: the nexus

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2014-01-01

The fat body in invertebrates was shown to participate in energy storage and homeostasis, apart from its other roles in immune mediation and protein synthesis to mention a few. Thus, sharing similar characteristics with the liver and adipose tissues in vertebrates. However, vertebrate adipose tissue or fat has been incriminated in the pathophysiology of metabolic disorders due to its role in production of pro-inflammatory cytokines. This has not been reported in the insect fat body. The link between the fat body and adipose tissue was examined in this review with the aim of determining the principal factors responsible for resistance to inflammation in the insect fat body. This could be the missing link in the prevention of metabolic disorders in vertebrates, occasioned by obesity. PMID:24758278

Mechanical homeostasis regulating adipose tissue volume

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Svedman Paul

2007-09-01

Full Text Available Abstract Background The total body adipose tissue volume is regulated by hormonal, nutritional, paracrine, neuronal and genetic control signals, as well as components of cell-cell or cell-matrix interactions. There are no known locally acting homeostatic mechanisms by which growing adipose tissue might adapt its volume. Presentation of the hypothesis Mechanosensitivity has been demonstrated by mesenchymal cells in tissue culture. Adipocyte differentiation has been shown to be inhibited by stretching in vitro, and a pathway for the response has been elucidated. In humans, intermittent stretching of skin for reconstructional purposes leads to thinning of adipose tissue and thickening of epidermis – findings matching those observed in vitro in response to mechanical stimuli. Furthermore, protracted suspension of one leg increases the intermuscular adipose tissue volume of the limb. These findings may indicate a local homeostatic adipose tissue volume-regulating mechanism based on movement-induced reduction of adipocyte differentiation. This function might, during evolution, have been of importance in confined spaces, where overgrowth of adipose tissue could lead to functional disturbance, as for instance in the turtle. In humans, adipose tissue near muscle might in particular be affected, for instance intermuscularly, extraperitoneally and epicardially. Mechanical homeostasis might also contribute to protracted maintainment of soft tissue shape in the face and neck region. Testing of the hypothesis Assessment of messenger RNA-expression of human adipocytes following activity in adjacent muscle is planned, and study of biochemical and volumetric adipose tissue changes in man are proposed. Implications of the hypothesis The interpretation of metabolic disturbances by means of adipose tissue might be influenced. Possible applications in the head and neck were discussed.

HIV Persistence in Adipose Tissue Reservoirs.

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Couturier, Jacob; Lewis, Dorothy E

2018-02-01

The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and

Cloning changes the response to obesity of innate immune factors in blood, liver, and adipose tissues in domestic pigs.

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Rødgaard, Tina; Skovgaard, Kerstin; Stagsted, Jan; Heegaard, Peter M H

2013-06-01

The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls as well as lean clones and controls. Generally, the variation in phenotype between individual pigs was not reduced in cloned siblings as compared to normal siblings. Therefore, we conclude that cloning limits both the number of genes responding to obesity as well as the degree of tissue-differentiated gene expression, concomitantly with an increase in APP serum concentrations only seen in cloned, obese pigs. This may suggest that the APP response seen in obese, cloned pigs is a consequence of the characteristic skewed gene response to obesity in cloned pigs, as described in this work. This should be taken into consideration when using cloned animals as models for innate responses to obesity.

Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue.

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Miao, Yifei; Wu, Wanfu; Dai, Yubing; Maneix, Laure; Huang, Bo; Warner, Margaret; Gustafsson, Jan-Åke

2015-11-10

The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

The Adipose Tissue in Farm Animals

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Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura

2014-01-01

and immune cells. The scientific interest in adipose tissue is largely based on the worldwide increasing prevalence of obesity in humans; in contrast, obesity is hardly an issue for farmed animals that are fed according to their well-defined needs. Adipose tissue is nevertheless of major importance...... in these animals, as the adipose percentage of the bodyweight is a major determinant for the efficiency of transferring nutrients from feed into food products and thus for the economic value from meat producing animals. In dairy animals, the importance of adipose tissue is based on its function as stromal...... and metabolic disorders. We herein provide a general overview of adipose tissue functions and its importance in farm animals. This review will summarize recent achievements in farm animal adipose tissue proteomics, mainly in cattle and pigs, but also in poultry, i.e. chicken and in farmed fish. Proteomics...

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

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Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice

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Braster, Quinte; Silvestre Roig, Carlos; Hartwig, Helene; Beckers, Linda; den Toom, Myrthe; Döring, Yvonne; Daemen, Mat J.; Lutgens, Esther; Soehnlein, Oliver

2016-01-01

Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of

Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

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Byung Young Park

Full Text Available It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2 and MMPs (MMP-2 and MMP-9, whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2 in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.

Is epicardial adipose tissue, assessed by echocardiography, a reliable method for visceral adipose tissue prediction?

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Silaghi, Alina Cristina; Poantă, Laura; Valea, Ana; Pais, Raluca; Silaghi, Horatiu

2011-03-01

Epicardial adipose tissue is an ectopic fat storage at the heart surface in direct contact with the coronary arteries. It is considered a metabolically active tissue, being a local source of pro-inflammatory factors that contribute to the pathogenesis of coronary artery disease. The AIM of our study was to establish correlations between echocardiographic assessment of epicardial adipose tissue and anthropometric and ultrasound measurements of the central and peripheral fat depots. The study was conducted on 22 patients with or without coronaropathy. Epicardial adipose tissue was measured using Aloka Prosound α 10 machine with a 3.5-7.5 MHz variable-frequency transducer and subcutaneous and visceral fat with Esaote Megas GPX machine and 3.5-7.5 MHz variable frequency transducer. Epicardial adipose tissue measured by echocardiography is correlated with waist circumference (p < 0.05), visceral adipose tissue thickness measured by ultrasonography (US) and is not correlated with body mass index (p = 0.315), hip and thigh circumference or subcutaneous fat thickness measured by US. Our study confirms that US assessment of epicardial fat correlates with anthropometric and US measurements of the central fat, representing an indirect but reliable marker of the visceral fat.

Inflammatory Signals shift from adipose to liver during high fat feeding and influence the development of steatohepatitis in mice

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Greenfeder Scott

2011-03-01

Full Text Available Abstract Background Obesity and inflammation are highly integrated processes in the pathogenesis of insulin resistance, diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Molecular mechanisms underlying inflammatory events during high fat diet-induced obesity are poorly defined in mouse models of obesity. This work investigated gene activation signals integral to the temporal development of obesity. Methods Gene expression analysis in multiple organs from obese mice was done with Taqman Low Density Array (TLDA using a panel of 92 genes representing cell markers, cytokines, chemokines, metabolic, and activation genes. Mice were monitored for systemic changes characteristic of the disease, including hyperinsulinemia, body weight, and liver enzymes. Liver steatosis and fibrosis as well as cellular infiltrates in liver and adipose tissues were analyzed by histology and immunohistochemistry. Results Obese C57BL/6 mice were fed with high fat and cholesterol diet (HFC for 6, 16 and 26 weeks. Here we report that the mRNA levels of macrophage and inflammation associated genes were strongly upregulated at different time points in adipose tissues (6-16 weeks and liver (16-26 weeks, after the start of HFC feeding. CD11b+ and CD11c+ macrophages highly infiltrated HFC liver at 16 and 26 weeks. We found clear evidence that signals for IL-1β, IL1RN, TNF-α and TGFβ-1 are present in both adipose and liver tissues and that these are linked to the development of inflammation and insulin resistance in the HFC-fed mice. Conclusions Macrophage infiltration accompanied by severe inflammation and metabolic changes occurred in both adipose and liver tissues with a temporal shift in these signals depending upon the duration of HFC feeding. The evidences of gene expression profile, elevated serum alanine aminotransferase, and histological data support a progression towards nonalcoholic fatty liver disease and steatohepatitis in these HFC-fed mice within the

Molecular signature of adipose tissue in patients with both non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS).

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Baranova, Ancha; Tran, Thuy Phuong; Afendy, Arian; Wang, Lei; Shamsaddini, Amirhossein; Mehta, Rohini; Chandhoke, Vikas; Birerdinc, Aybike; Younossi, Zobair M

2013-05-31

Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only. We included patients with biopsy-proven NAFLD and PCOS (N = 12) and BMI-matched biopsy-proven NAFLD patients without PCOS (N = 12). Expression levels of individual mRNAs and soluble serum biomarkers were compared by non-parametric Mann-Whitney test. The analysis also included Spearman rank correlation tests and multiple regression analysis. For co-correlated genes, the factor analysis was performed. The total serum levels of apoptotic biomarker M30 were significantly elevated in PCOS patients with liver steatosis as compared to non-PCOS NAFLD controls (P < 0.02), pointing that androgen-dependent proapoptotic PCOS environment that may directly contribute to NAFLD progression in these patients. Similarly, hyperandrogenism may explain the observed PCOS-specific decrease (P < 0.04) in adipose LDLR mRNA expression that may be connected to the proneness of PCOS patients to NAFLD. The levels of mRNA encoding angiogenesis-associated GSK-3B interacting protein ninein were also significantly increased in the adipose tissue of NAFLD patients with PCOS (P < 0.007). Furthermore, the levels of resistin positively correlated with expression levels of LDLR and prothrombin time (PT). An androgen-dependent proapoptotic PCOS environment may directly contribute to NAFLD progression in these patients. Hyperandrogenism may explain an observed decrease in adipose LDLR mRNA expression. An inflammation-associated increase in the release of resistin into circulation might contribute to the prothrombotic state observed

Obesity-induced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils (Meriones unguiculatus

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Luciana L.A. Ventura

2017-03-01

Full Text Available Background Nowadays, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This leads the body to a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to characterize the metabolic and adipose tissue changes resulting from a diet rich in fats and simple sugars in gerbils. Methods We divided 14 gerbils into two experimental groups that received a diet rich in simple carbohydrates and fats with 5,86 kcal/g (OB, n = 7 or a standard diet with 4.15 kcal/g (CT; n = 7 for 11 weeks. The animals had free access to water and food. The animal weight and food consumption were measured weekly. Blood, adipose tissue and liver of each animal were collected at the end of experiment. The following parameters were determined: cholesterol (COL, triglycerides (TGL and glycemia (GLI in the plasma; cytokines (IL-6, IL-10 and TNF-α and hormones (adiponectin and leptin in adipose tissue; activity of superoxide dismutase (SOD and catalase (CAT, extraction and differentiation of fat and histology in liver. Results The consumption of a diet rich in simple carbohydrates and fats led to increased total body weight and increased relative weights of liver and adipose tissue. In addition, we observed increased fasting glucose levels and circulating triglycerides, along with high TNF-α production in adipose tissue and increased total fat, cholesterol and triglyceride contents in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, the animals of this group showed depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels in

The role of active brown adipose tissue in human metabolism

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Ozguven, Salih; Turoglu, H.T. [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Ones, Tunc [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Kozyatagi/Kadikoy, Istanbul (Turkey); Yilmaz, Yusuf; Imeryuz, Nese [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Internal Medicine, Division of Gastroenterology, Istanbul (Turkey)

2016-02-15

The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing {sup 18}F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). We retrospectively and prospectively analysed the {sup 18}F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD. (orig.)

Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry.

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Sawada, Yoshikazu; Izumida, Yoshihiko; Takeuchi, Yoshinori; Aita, Yuichi; Wada, Nobuhiro; Li, EnXu; Murayama, Yuki; Piao, Xianying; Shikama, Akito; Masuda, Yukari; Nishi-Tatsumi, Makiko; Kubota, Midori; Sekiya, Motohiro; Matsuzaka, Takashi; Nakagawa, Yoshimi; Sugano, Yoko; Iwasaki, Hitoshi; Kobayashi, Kazuto; Yatoh, Shigeru; Suzuki, Hiroaki; Yagyu, Hiroaki; Kawakami, Yasushi; Kadowaki, Takashi; Shimano, Hitoshi; Yahagi, Naoya

2017-11-04

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks. TOFO-treated mice showed a decrease in fat mass and the effect of TOFO was attenuated in HVx group. Although both HVx and sham mice showed a similar level of reduction in hepatic glycogen by TOFO treatment, HVx mice exhibited an attenuated response in protein phosphorylation by protein kinase A (PKA) in white adipose tissue compared with the sham group. As PKA pathway is known to act as an effector of the liver-brain-adipose axis and activate triglyceride lipases in adipocytes, these results indicated that SGLT2 inhibition triggered glycogen depletion signal and actuated liver-brain-adipose axis, resulting in PKA activation in adipocytes. Taken together, it was concluded that the effect of SGLT2 inhibition on weight loss is in part mediated via the liver-brain-adipose neurocircuitry. Copyright © 2017 Elsevier Inc. All rights reserved.

Persistence of Coxiella burnetii, the agent of Q fever, in murine adipose tissue.

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Yassina Bechah

Full Text Available Coxiella burnetii, the agent of Q fever, is known to persist in humans and rodents but its cellular reservoir in hosts remains undetermined. We hypothesized that adipose tissue serves as a C. burnetii reservoir during bacterial latency. BALB/c and C57BL/6 mice were infected with C. burnetii by the intraperitoneal route or the intracheal route. Adipose tissue was tested for the presence of C. burnetii several months after infection. C. burnetii was detected in abdominal, inguinal and dorsal adipose tissue 4 months post-infection, when no bacteria were detected in blood, liver, lungs and spleen, regardless of the inoculation route and independently of mouse strain. The transfer of abdominal adipose tissue from convalescent BALB/c mice to naïve immunodeficient mice resulted in the infection of the recipient animals. It is likely that C. burnetii infects adipocytes in vivo because bacteria were found in adipocytes within adipose tissue and replicated within in vitro-differentiated adipocytes. In addition, C. burnetii induced a specific transcriptional program in in-vivo and in vitro-differentiated adipocytes, which was enriched in categories associated with inflammatory response, hormone response and cytoskeleton. These changes may account for bacterial replication in in-vitro and chronic infection in-vivo. Adipose tissue may be the reservoir in which C. burnetii persists for prolonged periods after apparent clinical cure. The mouse model of C. burnetii infection may be used to understand the relapses of Q fever and provide new perspectives to the follow-up of patients.

Phenylalanine kinetics in human adipose tissue.

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Coppack, S W; Persson, M; Miles, J M

1996-01-01

Very little is known about the regulation of protein metabolism in adipose tissue. In this study systemic, adipose tissue, and forearm phenylalanine kinetics were determined in healthy postabsorptive volunteers before and during a 2-h glucose infusion (7 mg.kg-1.min-1). [3H]Phenylalanine was infused and blood was sampled from a radial artery, a subcutaneous abdominal vein, and a deep forearm vein. Adipose tissue and forearm blood flow were measured with 133Xe and plethysmography, respectively...

Sleep deprivation affects inflammatory marker expression in adipose tissue

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Santos Ronaldo VT

2010-10-01

Full Text Available Abstract Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation. Methods The study consisted of two groups: a control (C group and a paradoxical sleep deprivation by 96 h (PSD group. Ten rats were randomly assigned to either the control group (C or the PSD. Mesenteric (MEAT and retroperitoneal (RPAT adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL-6, interleukin (IL-10 and tumour necrosis factor (TNF-α were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum. Results IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-α levels decreased in MEAT. Glucose, triglycerides (TG, VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased. Conclusion PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-α protein concentrations in MEAT and increased levels of corticosterone in serum.

Adipose Tissue as an Endocrine Organ: An Update on Pro-inflammatory and Anti-inflammatory Microenvironment

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Kvido Smitka

2015-01-01

Full Text Available Adipose tissue is recognized as an active endocrine organ that produces a number of endocrine substances referred to as “adipokines” including leptin, adiponectin, adipolin, visfatin, omentin, tumour necrosis factor-alpha (TNF-α, interleukin-6 (IL-6, resistin, pigment epithelium-derived factor (PEDF, and progranulin (PGRN which play an important role in the food intake regulation and significantly influence insulin sensitivity and in some cases directly affect insulin resistance in skeletal muscle, liver, and adipose tissue. The review summarizes current knowledge about adipose tissue-derived hormones and their influence on energy homeostasis regulation. The possible therapeutic potential of these adipokines in the treatment of insulin resistance, endothelial dysfunction, a pro-inflammatory response, obesity, eating disorders, progression of atherosclerosis, type 1 diabetes, and type 2 diabetes is discussed.

Noncanonical Wnt signaling promotes obesity-induced adipose tissue inflammation and metabolic dysfunction independent of adipose tissue expansion.

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Fuster, José J; Zuriaga, María A; Ngo, Doan Thi-Minh; Farb, Melissa G; Aprahamian, Tamar; Yamaguchi, Terry P; Gokce, Noyan; Walsh, Kenneth

2015-04-01

Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion. © 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.

Hepatic CEACAM1 Overexpression Protects Against Diet-induced Fibrosis and Inflammation in White Adipose Tissue

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Sumona Ghosh Lester

2015-08-01

Full Text Available CEACAM1 promotes insulin extraction, an event that occurs mainly in liver. Phenocopying global Ceacam1 null mice (Cc1–/–, C57/BL6J mice fed a high-fat diet exhibited reduced hepatic CEACAM1 levels and impaired insulin clearance, followed by hyperinsulinemia, insulin resistance and visceral obesity. Conversely, forced liver-specific expression of CEACAM1 protected insulin sensitivity and energy expenditure, and limited gain in total fat mass by high-fat diet in L-CC1 mice. Because CEACAM1 protein is barely detectable in white adipose tissue, we herein investigated whether hepatic CEACAM1-dependent insulin clearance pathways regulate adipose tissue biology in response to dietary fat. While high-fat diet caused a similar body weight gain in L-CC1, this effect was delayed and less intense relative to wild-type mice. Histological examination revealed less expansion of adipocytes in L-CC1 than wild-type by high-fat intake. Immunofluorescence analysis demonstrated a more limited recruitment of crown-like structures and qRT-PCR analysis showed no significant rise in TNFα mRNA levels in response to high-fat intake in L-CC1 than wild-type mice. Unlike wild-type, high-fat diet did not activate TGF-β in white adipose tissue of L-CC1 mice, as assessed by Western analysis of Smad2/3 phosphorylation. Consistently, high-fat diet caused relatively less collagen deposition in L-CC1 than wild-type mice, as shown by Trichome staining. Coupled with reduced lipid redistribution from liver to visceral fat, lower inflammation and fibrosis could contribute to protected energy expenditure against high-fat diet in L-CC1 mice. The data underscore the important role of hepatic insulin clearance in the regulation of adipose tissue inflammation and fibrosis.

Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats

DEFF Research Database (Denmark)

Liaset, Bjørn; Madsen, Lise; Hao, Qin

2009-01-01

levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal....../retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism....

Treating fructose-induced metabolic changes in mice with high-intensity interval training: insights in the liver, white adipose tissue, and skeletal muscle.

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Motta, Victor F; Bargut, Thereza L; Aguila, Marcia B; Mandarim-de-Lacerda, Carlos A

2017-10-01

Fructose-rich caloric sweeteners induce adverse changes in the metabolism of humans. The study evaluated the effects of high-intensity interval training (HIIT) on a fructose feeding model, focusing on the liver, white adipose tissue (WAT), skeletal muscle, and their interplay. Male C57BL/6 mice were fed for 18 wk one of the following diets: control (C; 5% of total energy from fructose) or fructose (F; 55% of total energy from fructose). In the 10th week, for an additional 8-wk period, the groups were divided into nontrained (NT) or HIIT groups, totaling four groups: C-NT, C-HIIT, F-NT, and F-HIIT. At the end of the experiment, fructose consumption in the F-NT group led to a high systolic blood pressure, high plasma triglycerides, insulin resistance with glucose intolerance, and lower insulin sensitivity. We also observed liver steatosis, adipocyte hypertrophy, and diminished gene expressions of peroxisome proliferator-activated receptor-γ coactivator 1-α and fibronectin type III domain containing 5 (FNDC5; irisin) in this F-NT group. These results were accompanied by decreased gene expressions of nuclear respiratory factor 1 and mitochondrial transcription factor A (markers of mitochondrial biogenesis), and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1 (markers of β-oxidation). HIIT improved all of these data in the C-HIIT and F-HIIT groups. In conclusion, in mice fed a fructose diet, HIIT improved body mass, blood pressure, glucose metabolism, and plasma triglycerides. Liver, WAT, and skeletal muscle were positively modulated by HIIT, indicating HIIT as a coadjutant treatment for diseases affecting these tissues. NEW & NOTEWORTHY We investigated the effects of high-intensity interval training (HIIT) in mice fed a fructose-rich diet and the resulting severe negative effect on the liver, white adipose tissue (WAT), and skeletal muscle, which reduced the expression of fibronectin type III domain containing 5 (FNDC5, irisin) and

Macrophage Area Content and Phenotype in Hepatic and Adipose Tissue in Patients with Obesity Undergoing Roux-en-Y Gastric Bypass

DEFF Research Database (Denmark)

Kristensen, Marianne D; Lund, Michael Taulo; Hansen, Merethe

2017-01-01

OBJECTIVE: To investigate hepatic and adipose tissue macrophage content in subjects with obesity and the role of adipose tissue macrophages in weight loss-induced improved insulin sensitivity (IS). METHODS: A cross-sectional and a longitudinal study were combined to investigate the role...... of macrophages in subcutaneous (SAT) and visceral (VAT) adipose tissue and the liver in obesity-induced impaired IS and improvements with weight loss. Macrophage markers (CD68, CD163, and CD206) in SAT, VAT, and the liver from patients with obesity were investigated. The same macrophage markers were investigated...... in SAT from 18 patients with obesity before and ∼18 months after a diet- and Roux-en-Y gastric bypass-induced weight loss. RESULTS: SAT macrophage markers did not decrease with weight loss, but macrophage concentration may have increased, concomitant with improved IS. Hepatic macrophage markers did...

Injectable biomaterials for adipose tissue engineering

International Nuclear Information System (INIS)

Young, D A; Christman, K L

2012-01-01

Adipose tissue engineering has recently gained significant attention from materials scientists as a result of the exponential growth of soft tissue filler procedures being performed within the clinic. While several injectable materials are currently being marketed for filling subcutaneous voids, they often face limited longevity due to rapid resorption. Their inability to encourage natural adipose formation or ingrowth necessitates repeated injections for a prolonged effect and thus classifies them as temporary fillers. As a result, a significant need for injectable materials that not only act as fillers but also promote in vivo adipogenesis is beginning to be realized. This paper will discuss the advantages and disadvantages of commercially available soft tissue fillers. It will then summarize the current state of research using injectable synthetic materials, biopolymers and extracellular matrix-derived materials for adipose tissue engineering. Furthermore, the successful attributes observed across each of these materials will be outlined along with a discussion of the current difficulties and future directions for adipose tissue engineering. (paper)

[Human brown adipose tissue].

Science.gov (United States)

Virtanen, Kirsi A; Nuutila, Pirjo

2015-01-01

Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

Adipose tissue-derived stem cells in oral mucosa tissue engineering ...

African Journals Online (AJOL)

Jane

2011-10-10

Oct 10, 2011 ... stem cells (ADSCs) may play an important role in this field. In this research ..... Adipose tissue is derived from embryonic mesodermal precursors and .... Clonogenic multipotent stem cells in human adipose tissue differentiate ...

Intrahepatic fat, abdominal adipose tissues, and metabolic state: magnetic resonance imaging study.

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Yaskolka Meir, Anat; Tene, Lilac; Cohen, Noa; Shelef, Ilan; Schwarzfuchs, Dan; Gepner, Yftach; Zelicha, Hila; Rein, Michal; Bril, Nitzan; Serfaty, Dana; Kenigsbuch, Shira; Chassidim, Yoash; Sarusy, Benjamin; Dicker, Dror; Thiery, Joachim; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

2017-07-01

Intrahepatic fat (IHF) is best known to associate with waist circumference (WC) and visceral adipose tissue (VAT), but its relation to abdominal subcutaneous adipose tissue is controversial. While IHF ≥ 5% dichotomously defines fatty liver, %IHF is rarely considered as a continuous variable that includes the normal range. In this study, we aimed to evaluate %IHF association with abdominal fat subdepots, pancreatic, and renal-sinus fats. We evaluated %IHF, abdominal fat subdepots, %pancreatic, and renal-sinus fats, among individuals with moderate abdominal obesity, using 3-Tesla magnetic resonance imaging. Among 275 participants, %IHF widely ranged (0.01%-50.4%) and was lower in women (1.6%) than men (7.3%; P fat was positively associated with %IHF (P = .005). In an age, sex, WC, and VAT-adjusted models, elevated liver enzymes, glycemic, lipid, and inflammatory biomarkers were associated with increased %IHF (P fat is differentially associated with abdominal fat subdepots. Intrahepatic-fat as a continuous variable could be predicted by specific traditional parameters, even within the current normal range, and partially independent of VAT. Copyright © 2017 John Wiley & Sons, Ltd.

Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice

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Sabrina Le Bouter

2010-01-01

Full Text Available Rosiglitazone (RSG, developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d with untreated non-diabetic littermates (db/+. For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs and free fatty acids (FFAs in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.

Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue.

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Mohamed Asrih

Full Text Available Beside its beneficial effects on weight loss, ketogenic diet (KD causes dyslipidemia, a pro-inflammatory state involved in the development of hepatic steatosis, glucose intolerance and insulin resistance, although the latter is still being debated. Additionally, KD is known to increase fibroblast growth factor 21 (FGF21 plasma levels. However, FGF21 cannot initiate its beneficial actions on metabolism in these conditions. We therefore hypothesized and tested in the present study that KD may impair FGF21 signaling.Using indirect calorimetry, we found that KD-fed mice exhibited higher energy expenditure than regular chow (RC-fed mice associated with increased Ucp1 levels in white adipose tissue (WAT, along with increased plasma FGF21 levels. We then assessed the effect of KD on FGF21 signaling in both the liver and WAT. We found that Fgfr4 and Klb (β-klotho were downregulated in the liver, while Fgfr1 was downregulated in WAT of KD-fed mice. Because inflammation could be one of the mechanisms linking KD to impaired FGF21 signaling, we measured the expression levels of inflammatory markers and macrophage accumulation in WAT and liver and found an increased inflammation and macrophage accumulation in the liver, but surprisingly, a reduction of inflammation in WAT.We also showed that KD enhances lipid accumulation in the liver, which may explain hepatic inflammation and impaired Fgfr4 and Klb expression. In contrast, import of lipids from the circulation was significantly reduced in WAT of KD-fed mice, as suggested by a downregulation of Lpl and Cd36. This was further associated with reduced inflammation in WAT.Altogether, these results indicate that KD could be beneficial for a given tissue but deleterious for another.

G0S2: A small giant controller of lipolysis and adipose-liver fatty acid flux.

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Zhang, Xiaodong; Heckmann, Bradlee L; Campbell, Latoya E; Liu, Jun

2017-10-01

The discovery of adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) provided a major paradigm shift in the understanding of intracellular lipolysis in both adipocytes and nonadipocyte cells. The subsequent discovery of G0/G1 switch gene 2 (G0S2) as a potent endogenous inhibitor of ATGL revealed a unique mechanism governing lipolysis and fatty acid (FA) availability. G0S2 is highly conserved in vertebrates, and exhibits cyclical expression pattern between adipose tissue and liver that is critical to lipid flux and energy homeostasis in these two tissues. Biochemical and cell biological studies have demonstrated that a direct interaction with ATGL mediates G0S2's inhibitory effects on lipolysis and lipid droplet degradation. In this review we examine evidence obtained from recent in vitro and in vivo studies that lends support to the proof-of-principle concept that G0S2 functions as a master regulator of tissue-specific balance of TG storage vs. mobilization, partitioning of metabolic fuels between adipose and liver, and the whole-body adaptive energy response. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance.

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Baranova, Ancha; Gowder, Shobha J; Schlauch, Karen; Elariny, Hazem; Collantes, Rochelle; Afendy, Arian; Ong, Janus P; Goodman, Zachary; Chandhoke, Vikas; Younossi, Zobair M

2006-09-01

Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.

Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity

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We studied the effects of weight loss induced by either a low-fat normal diet or restriction of high-fat diet on hepatic steatosis, inflammation in the liver and adipose tissue, and blood monocytes of obese mice. In mice with high-fat diet-induced obesity, weight loss was achieved by switching from ...

Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.

LENUS (Irish Health Repository)

Lynch, Lydia

2012-09-21

Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.

Insulin Signaling in Liver and Adipose Tissues in Periparturient Dairy Cows Supplemented with Dietary Nicotinic Acid.

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Kinoshita, Asako; Kenéz, Ákos; Locher, Lena; Meyer, Ulrich; Dänicke, Sven; Rehage, Jürgen; Huber, Korinna

2016-01-01

The glucose homeostasis in dairy cattle is very well controlled, in line with the metabolic adaptation during the periparturient period. Former studies showed that nicotinic acid (NA) lowered plasma non-esterified fatty acids (NEFA) concentrations and increased insulin sensitivity in dairy cows. Thus, the purpose of this study was to investigate whether the expression of proteins involved in hepatic and adipose insulin signaling and protein expression of hepatic glucose transporter 2 (GLUT2) were affected by dietary NA and dietary concentrate intake in periparturient dairy cows. Twenty pluriparous German Holstein cows were fed with the same diet from about 21 days before the expected calving date (d-21) to calving. After calving, cows were randomly assigned in 4 groups and fed with diets different in concentrate proportion ("HC" with 60:40% or "LC" with 30:70% concentrate-to-roughage ratio) and supplemented with NA (24 g/day) (NA) or without (CON) until d21. Biopsy samples were taken from the liver, subcutaneous (SCAT) and retroperitoneal (RPAT) adipose tissues at d-21 and d21. Protein expression of insulin signaling molecules (insulin receptor (INSR), phosphatidylinositol-3-kinase (PI3K), protein kinase Cζ (PKCζ)) and hepatic GLUT2 was measured by Western Blotting. The ratio of protein expression at d21/at d-21 was calculated and statistically evaluated for the effects of time and diet. Cows in HC had significantly higher dietary energy intake than cows in LC. In RPAT a decrease in PI3K and PKCζ expression was found in all groups, irrespectively of diet. In the liver, the GLUT2 expression was significantly lower in cows in NA compared with cows in CON. In conclusion, insulin signaling might be decreased in RPAT over time without any effect of diet. NA was able to modulate hepatic GLUT2 expression, but its physiological role is unclear.

Insulin Signaling in Liver and Adipose Tissues in Periparturient Dairy Cows Supplemented with Dietary Nicotinic Acid.

Directory of Open Access Journals (Sweden)

Asako Kinoshita

Full Text Available The glucose homeostasis in dairy cattle is very well controlled, in line with the metabolic adaptation during the periparturient period. Former studies showed that nicotinic acid (NA lowered plasma non-esterified fatty acids (NEFA concentrations and increased insulin sensitivity in dairy cows. Thus, the purpose of this study was to investigate whether the expression of proteins involved in hepatic and adipose insulin signaling and protein expression of hepatic glucose transporter 2 (GLUT2 were affected by dietary NA and dietary concentrate intake in periparturient dairy cows. Twenty pluriparous German Holstein cows were fed with the same diet from about 21 days before the expected calving date (d-21 to calving. After calving, cows were randomly assigned in 4 groups and fed with diets different in concentrate proportion ("HC" with 60:40% or "LC" with 30:70% concentrate-to-roughage ratio and supplemented with NA (24 g/day (NA or without (CON until d21. Biopsy samples were taken from the liver, subcutaneous (SCAT and retroperitoneal (RPAT adipose tissues at d-21 and d21. Protein expression of insulin signaling molecules (insulin receptor (INSR, phosphatidylinositol-3-kinase (PI3K, protein kinase Cζ (PKCζ and hepatic GLUT2 was measured by Western Blotting. The ratio of protein expression at d21/at d-21 was calculated and statistically evaluated for the effects of time and diet. Cows in HC had significantly higher dietary energy intake than cows in LC. In RPAT a decrease in PI3K and PKCζ expression was found in all groups, irrespectively of diet. In the liver, the GLUT2 expression was significantly lower in cows in NA compared with cows in CON. In conclusion, insulin signaling might be decreased in RPAT over time without any effect of diet. NA was able to modulate hepatic GLUT2 expression, but its physiological role is unclear.

Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

Science.gov (United States)

Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

2016-01-01

Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues

Functional Characterization of Preadipocytes Derived from Human Periaortic Adipose Tissue

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Diana Vargas

2017-01-01

Full Text Available Adipose tissue can affect the metabolic control of the cardiovascular system, and its anatomic location can affect the vascular function differently. In this study, biochemical and phenotypical characteristics of adipose tissue from periaortic fat were evaluated. Periaortic and subcutaneous adipose tissues were obtained from areas surrounding the ascending aorta and sternotomy incision, respectively. Adipose tissues were collected from patients undergoing myocardial revascularization or mitral valve replacement surgery. Morphological studies with hematoxylin/eosin and immunohistochemical assay were performed in situ to quantify adipokine expression. To analyze adipogenic capacity, adipokine expression, and the levels of thermogenic proteins, adipocyte precursor cells were isolated from periaortic and subcutaneous adipose tissues and induced to differentiation. The precursors of adipocytes from the periaortic tissue accumulated less triglycerides than those from the subcutaneous tissue after differentiation and were smaller than those from subcutaneous adipose tissue. The levels of proteins involved in thermogenesis and energy expenditure increased significantly in periaortic adipose tissue. Additionally, the expression levels of adipokines that affect carbohydrate metabolism, such as FGF21, increased significantly in mature adipocytes induced from periaortic adipose tissue. These results demonstrate that precursors of periaortic adipose tissue in humans may affect cardiovascular events and might serve as a target for preventing vascular diseases.

The role of adipose tissue in cancer-associated cachexia.

Science.gov (United States)

Vaitkus, Janina A; Celi, Francesco S

2017-03-01

Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing

Subcutaneous adipose tissue classification

Directory of Open Access Journals (Sweden)

A. Sbarbati

2010-11-01

Full Text Available The developments in the technologies based on the use of autologous adipose tissue attracted attention to minor depots as possible sampling areas. Some of those depots have never been studied in detail. The present study was performed on subcutaneous adipose depots sampled in different areas with the aim of explaining their morphology, particularly as far as regards stem niches. The results demonstrated that three different types of white adipose tissue (WAT can be differentiated on the basis of structural and ultrastructural features: deposit WAT (dWAT, structural WAT (sWAT and fibrous WAT (fWAT. dWAT can be found essentially in large fatty depots in the abdominal area (periumbilical. In the dWAT, cells are tightly packed and linked by a weak net of isolated collagen fibers. Collagenic components are very poor, cells are large and few blood vessels are present. The deep portion appears more fibrous then the superficial one. The microcirculation is formed by thin walled capillaries with rare stem niches. Reinforcement pericyte elements are rarely evident. The sWAT is more stromal; it is located in some areas in the limbs and in the hips. The stroma is fairly well represented, with a good vascularity and adequate staminality. Cells are wrapped by a basket of collagen fibers. The fatty depots of the knees and of the trochanteric areas have quite loose meshes. The fWAT has a noteworthy fibrous component and can be found in areas where a severe mechanic stress occurs. Adipocytes have an individual thick fibrous shell. In conclusion, the present study demonstrates evident differences among subcutaneous WAT deposits, thus suggesting that in regenerative procedures based on autologous adipose tissues the sampling area should not be randomly chosen, but it should be oriented by evidence based evaluations. The structural peculiarities of the sWAT, and particularly of its microcirculation, suggest that it could represent a privileged source for

Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

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Sung Sik eChoe

2016-04-01

Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment

DEFF Research Database (Denmark)

Tobin, L; Simonsen, L; Bülow, J

2010-01-01

The adipose tissue metabolism is dependent on its blood perfusion. During lipid mobilization e.g. during exercise and during lipid deposition e.g. postprandial, adipose tissue blood flow is increased. This increase in blood flow may involve capillary recruitment in the tissue. We investigated...... of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain......-gauge plethysmography was used to measure the adipose tissue and forearm blood flow, respectively. Ultrasound signal intensity of the first plateau phases was 27 ± dB in the abdominal subcutaneous adipose tissue and 18 ± 2 dB (P

Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs.

Science.gov (United States)

Mentzel, Caroline M Junker; Cardoso, Tainã Figueiredo; Pipper, Christian Bressen; Jacobsen, Mette Juul; Jørgensen, Claus Bøttcher; Cirera, Susanna; Fredholm, Merete

2018-02-01

The aim of this study was to elucidate the relative impact of three phenotypes often used to characterize obesity on perturbation of molecular pathways involved in obesity. The three obesity-related phenotypes are (1) body mass index (BMI), (2) amount of subcutaneous adipose tissue (SATa), and (3) amount of retroperitoneal adipose tissue (RPATa). Although it is generally accepted that increasing amount of RPATa is 'unhealthy', a direct comparison of the relative impact of the three obesity-related phenotypes on gene expression has, to our knowledge, not been performed previously. We have used multiple linear models to analyze altered gene expression of selected obesity-related genes in tissues collected from 19 female pigs phenotypically characterized with respect to the obesity-related phenotypes. Gene expression was assessed by high-throughput qPCR in RNA from liver, skeletal muscle and abdominal adipose tissue. The stringent statistical approach used in the study has increased the power of the analysis compared to the classical approach of analysis in divergent groups of individuals. Our approach led to the identification of key components of cellular pathways that are modulated in the three tissues in association with changes in the three obesity-relevant phenotypes (BMI, SATa and RPATa). The deregulated pathways are involved in biosynthesis and transcript regulation in adipocytes, in lipid transport, lipolysis and metabolism, and in inflammatory responses. Deregulation seemed more comprehensive in liver (23 genes) compared to abdominal adipose tissue (10 genes) and muscle (3 genes). Notably, the study supports the notion that excess amount of intra-abdominal adipose tissue is associated with a greater metabolic disease risk. Our results provide molecular support for this notion by demonstrating that increasing amount of RPATa has a higher impact on perturbation of cellular pathways influencing obesity and obesity-related metabolic traits compared to increase

Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

Science.gov (United States)

Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

2010-04-09

Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

Adenovirus 36 DNA in human adipose tissue.

Science.gov (United States)

Ponterio, E; Cangemi, R; Mariani, S; Casella, G; De Cesare, A; Trovato, F M; Garozzo, A; Gnessi, L

2015-12-01

Recent studies have suggested a possible correlation between obesity and adenovirus 36 (Adv36) infection in humans. As information on adenoviral DNA presence in human adipose tissue are limited, we evaluated the presence of Adv36 DNA in adipose tissue of 21 adult overweight or obese patients. Total DNA was extracted from adipose tissue biopsies. Virus detection was performed using PCR protocols with primers against specific Adv36 fiber protein and the viral oncogenic E4orf1 protein nucleotide sequences. Sequences were aligned with the NCBI database and phylogenetic analyses were carried out with MEGA6 software. Adv36 DNA was found in four samples (19%). This study indicates that some individuals carry Adv36 in the visceral adipose tissue. Further studies are needed to determine the specific effect of Adv36 infection on adipocytes, the prevalence of Adv36 infection and its relationship with obesity in the perspective of developing a vaccine that could potentially prevent or mitigate infection.

Automatic segmentation of abdominal organs and adipose tissue compartments in water-fat MRI: Application to weight-loss in obesity.

Science.gov (United States)

Shen, Jun; Baum, Thomas; Cordes, Christian; Ott, Beate; Skurk, Thomas; Kooijman, Hendrik; Rummeny, Ernst J; Hauner, Hans; Menze, Bjoern H; Karampinos, Dimitrios C

2016-09-01

To develop a fully automatic algorithm for abdominal organs and adipose tissue compartments segmentation and to assess organ and adipose tissue volume changes in longitudinal water-fat magnetic resonance imaging (MRI) data. Axial two-point Dixon images were acquired in 20 obese women (age range 24-65, BMI 34.9±3.8kg/m(2)) before and after a four-week calorie restriction. Abdominal organs, subcutaneous adipose tissue (SAT) compartments (abdominal, anterior, posterior), SAT regions along the feet-head direction and regional visceral adipose tissue (VAT) were assessed by a fully automatic algorithm using morphological operations and a multi-atlas-based segmentation method. The accuracy of organ segmentation represented by Dice coefficients ranged from 0.672±0.155 for the pancreas to 0.943±0.023 for the liver. Abdominal SAT changes were significantly greater in the posterior than the anterior SAT compartment (-11.4%±5.1% versus -9.5%±6.3%, pabdominal adipose tissue and organ segmentation, and allowed the detection of SAT and VAT subcompartments changes during weight loss. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

DEFF Research Database (Denmark)

Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

1999-01-01

Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We rep...

Neutron organ dose and the influence of adipose tissue

Science.gov (United States)

Simpkins, Robert Wayne

Neutron fluence to dose conversion coefficients have been assessed considering the influences of human adipose tissue. Monte Carlo code MCNP4C was used to simulate broad parallel beam monoenergetic neutrons ranging in energy from thermal to 10 MeV. Simulated Irradiations were conducted for standard irradiation geometries. The targets were on gender specific mathematical anthropomorphic phantoms modified to approximate human adipose tissue distributions. Dosimetric analysis compared adipose tissue influence against reference anthropomorphic phantom characteristics. Adipose Male and Post-Menopausal Female Phantoms were derived introducing interstitial adipose tissue to account for 22 and 27 kg additional body mass, respectively, each demonstrating a Body Mass Index (BMI) of 30. An Adipose Female Phantom was derived introducing specific subcutaneous adipose tissue accounting for 15 kg of additional body mass demonstrating a BMI of 26. Neutron dose was shielded in the superficial tissues; giving rise to secondary photons which dominated the effective dose for Incident energies less than 100 keV. Adipose tissue impact on the effective dose was a 25% reduction at the anterior-posterior incidence ranging to a 10% increase at the lateral incidences. Organ dose impacts were more distinctive; symmetrically situated organs demonstrated a 15% reduction at the anterior-posterior Incidence ranging to a 2% increase at the lateral incidences. Abdominal or asymmetrically situated organs demonstrated a 50% reduction at the anterior-posterior incidence ranging to a 25% increase at the lateral incidences.

Aging and Adipose Tissue: Potential Interventions for Diabetes and Regenerative Medicine

Science.gov (United States)

Palmer, Allyson K.; Kirkland, James L.

2016-01-01

Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies. PMID:26924669

Contact with existing adipose tissue is inductive for adipogenesis in matrigel.

LENUS (Irish Health Repository)

Kelly, John L

2006-07-01

The effect of adipose tissue on inductive adipogenesis within Matrigel (BD Biosciences) was assessed by using a murine chamber model containing a vascular pedicle. Three-chamber configurations that varied in the access to an adipose tissue source were used, including sealed- and open-chamber groups that had no access and limited access, respectively, to the surrounding adipose tissue, and a sealed-chamber group in which adipose tissue was placed as an autograft. All groups showed neovascularization, but varied in the amount of adipogenesis seen in direct relation to their access to preexisting adipose tissue: open chambers showed strong adipogenesis, whereas the sealed chambers had little or no adipose tissue; adipogenesis was restored in the autograft chamber group that contained 2- to 5-mg fat autografts. These showed significantly more adipogenesis than the sealed chambers with no autograft ( p < 0.01). Autografts with 1mg of fat were capable of producing adipogenesis but did so less consistently than the larger autografts. These findings have important implications for adipose tissue engineering strategies and for understanding de novo production of adipose tissue.

The effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Dirk Vissers

Full Text Available Excessive visceral adipose tissue appears to trigger a cascade of metabolic disturbances that seem to coexist with ectopic fat storage in muscle, liver, heart and the ß-cell. Therefore, the reduction of visceral adipose tissue potentially plays a pivotal role in the treatment of the metabolic syndrome. The purpose of this systematic review and meta-analysis is to describe the overall effect of exercise on visceral adipose tissue and to provide an overview of the effect of different exercise regimes, without caloric restriction, on visceral adipose tissue in obese persons. A systematic literature search was performed according to the PRISMA statement for reporting systematic reviews and meta-analyses. The initial search resulted in 87 articles after removing duplicates. After screening on title, abstract and full-text 15 articles (totalling 852 subjects fulfilled the a priori inclusion criteria. The quality of each eligible study was assessed in duplicate with "The Critical Review Form for Quantitative Studies". Using random-effects weights, the standardized mean difference (Hedge's g of the change in visceral adipose tissue was -0.497 with a 95% confidence interval of -0.655 to -0.340. The Z-value was -6.183 and the p-value (two tailed was <0.001. A subgroup analysis was performed based on gender, type of training and intensity. Aerobic training of moderate or high intensity has the highest potential to reduce visceral adipose tissue in overweight males and females. These results suggest that an aerobic exercise program, without hypocaloric diet, can show beneficial effects to reduce visceral adipose tissue with more than 30 cm(2 (on CT analysis in women and more than 40 cm(2 in men, even after 12 weeks.

Ghrelin receptor regulates adipose tissue inflammation in aging.

Science.gov (United States)

Lin, Ligen; Lee, Jong Han; Buras, Eric D; Yu, Kaijiang; Wang, Ruitao; Smith, C Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

2016-01-01

Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.

Non-invasive Assessments of Adipose Tissue Metabolism In Vitro.

Science.gov (United States)

Abbott, Rosalyn D; Borowsky, Francis E; Quinn, Kyle P; Bernstein, David L; Georgakoudi, Irene; Kaplan, David L

2016-03-01

Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with non-invasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored.

Growth hormone and adipose tissue: beyond the adipocyte.

Science.gov (United States)

Berryman, Darlene E; List, Edward O; Sackmann-Sala, Lucila; Lubbers, Ellen; Munn, Rachel; Kopchick, John J

2011-06-01

The last two decades have seen resurgence in research focused on adipose tissue. In part, the enhanced interest stems from an alarming increase in obesity rates worldwide. However, an understanding that this once simple tissue is significantly more intricate and interactive than previously realized has fostered additional attention. While few would argue that growth hormone (GH) radically alters fat mass, newer findings revealing the complexity of adipose tissue requires that GH's influence on this tissue be reexamined. Therefore, the objective of this review is to describe the more recent understanding of adipose tissue and to summarize our current knowledge of how GH may influence and contribute to these newer complexities of this tissue with special focus on the available data from mice with altered GH action. Copyright © 2011 Elsevier Ltd. All rights reserved.

Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

DEFF Research Database (Denmark)

Sun, Kai; Park, Jiyoung; Gupta, Olga T

2014-01-01

to demonstrate that endotrophin plays a pivotal role in shaping a metabolically unfavourable microenvironment in adipose tissue during consumption of a high-fat diet (HFD). Endotrophin serves as a powerful co-stimulator of pathologically relevant pathways within the 'unhealthy' adipose tissue milieu, triggering...

Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

International Nuclear Information System (INIS)

Lanza-Jacoby, S.; Tabares, A.

1990-01-01

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of [2-3H]glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats

Metabolic Circuit Involving Free Fatty Acids, microRNA 122, and Triglyceride Synthesis in Liver and Muscle Tissues.

Science.gov (United States)

Chai, Chofit; Rivkin, Mila; Berkovits, Liav; Simerzin, Alina; Zorde-Khvalevsky, Elina; Rosenberg, Nofar; Klein, Shiri; Yaish, Dayana; Durst, Ronen; Shpitzen, Shoshana; Udi, Shiran; Tam, Joseph; Heeren, Joerg; Worthmann, Anna; Schramm, Christoph; Kluwe, Johannes; Ravid, Revital; Hornstein, Eran; Giladi, Hilla; Galun, Eithan

2017-11-01

Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of Luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines. We measured levels of microRNAs and mRNAs by quantitative real-time PCR analysis of RNA extracted from plasma, liver, muscle, and adipose tissues of C57BL/6 mice given the FFA-inducer CL316243. MIR122 was inhibited using an inhibitor of MIR122. Metabolic profiles of mice were determined using metabolic chambers and by histologic analyses of liver tissues. We performed RNA sequence analyses to identify metabolic pathways involving MIR122. We validated human Agpat1 and Dgat1 mRNAs, involved in triglyceride synthesis, as targets of MIR122. FFAs increased MIR122 expression in livers of mice by activating the retinoic acid-related orphan receptor alpha, and induced secretion of MIR122 from liver to blood. Circulating MIR122 entered muscle and adipose tissues of mice, reducing mRNA levels of genes involved in triglyceride synthesis. Mice injected with an inhibitor of MIR122 and then given CL316243, accumulated triglycerides in liver and muscle tissues, and had reduced rates of β-oxidation. There was a positive correlation between level of FFAs and level of MIR122 in plasma samples from 6 healthy individuals, collected before and during fasting. In biochemical and histologic studies of plasma, liver, muscle, and adipose tissues from mice, we found that FFAs increase hepatic expression and secretion of MIR122, which regulates energy storage vs expenditure in liver and peripheral tissues. Strategies to reduce

Carotenoids in Adipose Tissue Biology and Obesity.

Science.gov (United States)

Bonet, M Luisa; Canas, Jose A; Ribot, Joan; Palou, Andreu

2016-01-01

Cell, animal and human studies dealing with carotenoids and carotenoid derivatives as nutritional regulators of adipose tissue biology with implications for the etiology and management of obesity and obesity-related metabolic diseases are reviewed. Most studied carotenoids in this context are β-carotene, cryptoxanthin, astaxanthin and fucoxanthin, together with β-carotene-derived retinoids and some other apocarotenoids. Studies indicate an impact of these compounds on essential aspects of adipose tissue biology including the control of adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress and the production of adipose tissue-derived regulatory signals and inflammatory mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in brown and white adipocytes, and counteract obesity in animal models. Intake, blood levels and adipocyte content of carotenoids are reduced in human obesity. Specifically designed human intervention studies in the field, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. In summary, studies support a role of specific carotenoids and carotenoid derivatives in the prevention of excess adiposity, and suggest that carotenoid requirements may be dependent on body composition.

Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

Directory of Open Access Journals (Sweden)

Andrew A. Bremer

2013-01-01

Full Text Available The metabolic syndrome (MetS confers an increased risk for both type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin, as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

Liver fat contents, abdominal adiposity and insulin resistance in non-diabetic prevalent hemodialysis patients.

Science.gov (United States)

Chen, Hung-Yuan; Lin, Chien-Chu; Chiu, Yen-Ling; Hsu, Shih-Ping; Pai, Mei-Fen; Yang, Ju-Yeh; Wu, Hon-Yen; Peng, Yu-Sen

2014-01-01

The liver fat contents and abdominal adiposity correlate well with insulin resistance (IR) in the general population. However, the relationship between liver fat content, abdominal adiposity and IR in non-diabetic hemodialysis (HD) patients remains unclear. This study aimed to clarify the associations among these factors. This is a cross-sectional, observational study. All patients received abdominal ultrasound for liver fat content. Abdominal adiposity was quantified with the conicity index (Ci) and waist circumference (WC). We checked the homeostasis model assessment for insulin resistance index (HOMA-IR) for IR. A total of 112 patients (60 women) were analyzed. Subjects with higher liver fat contents and WC had higher IR indices. But Ci did not correlate with IR indices. In both the multi-variable linear regression model and the logistic regression model, only higher liver fat content predicted a severe IR status. Liver fat contents have a remarkable correlation with IR; however, abdominal adiposity, measured either by Ci or WC, dose not independently correlate with IR in non-diabetic prevalent HD patients. © 2014 S. Karger AG, Basel.

Adipose tissue macrophages: going off track during obesity

NARCIS (Netherlands)

Boutens, L.; Stienstra, R.

2016-01-01

Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically

Differential effects of diet composition and timing of feeding behavior on rat brown adipose tissue and skeletal muscle peripheral clocks.

NARCIS (Netherlands)

De Goede, P.; Sen, Satish; Oosterman, Johanneke E; Kalsbeek, A.

2018-01-01

The effects of feeding behavior and diet composition,as well as their possible interactions,on daily (clock) gene expression rhythms have mainly been studied in the liver, and to a lesser degree in white adipose tissue(WAT), but hardly in other metabolic tissues such as skeletal muscle (SM) and

Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome

Science.gov (United States)

Paniagua, Juan Antonio

2016-01-01

Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering high-density lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS. PMID

Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome

Institute of Scientific and Technical Information of China (English)

Juan; Antonio; Paniagua[1,2

2016-01-01

Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat.Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia,hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose.Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering highdensity lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS.

Does bariatric surgery improve adipose tissue function?

Science.gov (United States)

Frikke-Schmidt, H.; O’Rourke, R. W.; Lumeng, C. N.; Sandoval, D. A.; Seeley, R. J.

2017-01-01

Summary Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. PMID:27272117

Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function

DEFF Research Database (Denmark)

Mottillo, Emilio P; Desjardins, Eric M; Crane, Justin D

2016-01-01

Brown (BAT) and white (WAT) adipose tissues play distinct roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The AMP-activated protein kinase (AMPK) is a cellular energy sensor, but its role...

Automatic Segmentation of Abdominal Adipose Tissue in MRI

DEFF Research Database (Denmark)

Mosbech, Thomas Hammershaimb; Pilgaard, Kasper; Vaag, Allan

2011-01-01

of intensity in-homogeneities. This effect is estimated by a thin plate spline extended to fit two classes of automatically sampled intensity points in 3D. Adipose tissue pixels are labelled with fuzzy c-means clustering and locally determined thresholds. The visceral and subcutaneous adipose tissue...

Mycobacterium canettii Infection of Adipose Tissues.

Science.gov (United States)

Bouzid, Fériel; Brégeon, Fabienne; Poncin, Isabelle; Weber, Pascal; Drancourt, Michel; Canaan, Stéphane

2017-01-01

Adipose tissues were shown to host Mycobacterium tuberculosis which is persisting inside mature adipocytes. It remains unknown whether this holds true for Mycobacterium canettii , a rare representative of the M. tuberculosis complex responsible for lymphatic and pulmonary tuberculosis. Here, we infected primary murine white and brown pre-adipocytes and murine 3T3-L1 pre-adipocytes and mature adipocytes with M. canettii and M. tuberculosis as a positive control. Both mycobacteria were able to infect 18-22% of challenged primary murine pre-adipocytes; and to replicate within these cells during a 7-day experiment with the intracellular inoculums being significantly higher in brown than in white pre-adipocytes for M. canettii ( p = 0.02) and M. tuberculosis ( p = 0.03). Further in-vitro infection of 3T3-L1 mature adipocytes yielded 9% of infected cells by M. canettii and 17% of infected cells by M. tuberculosis ( p = 0.001). Interestingly, M. canettii replicated and accumulated intra-cytosolic lipid inclusions within mature adipocytes over a 12-day experiment; while M. tuberculosis stopped replicating at day 3 post-infection. These results indicate that brown pre-adipocytes could be one of the potential targets for M. tuberculosis complex mycobacteria; and illustrate differential outcome of M. tuberculosis complex mycobacteria into adipose tissues. While white adipose tissue is an unlikely sanctuary for M. canettii , it is still an open question whether M. canettii and M. tuberculosis could persist in brown adipose tissues.

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

Directory of Open Access Journals (Sweden)

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.

Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

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LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

2016-02-01

The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

Maternal sodium butyrate supplement elevates the lipolysis in adipose tissue and leads to lipid accumulation in offspring liver of weaning-age rats.

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Zhou, Jiabin; Gao, Shixing; Chen, Jinglong; Zhao, Ruqian; Yang, Xiaojing

2016-07-22

Sodium butyrate (SB) is reported to regulate lipid metabolism in mammals, and the relationship between maternal nutrition and offspring growth has drawn much attention in the last several years. To elucidate the effects of maternal dietary SB supplementation on hepatic lipid metabolism in weaning rats, we fed 16 primiparous purebred female SD rats either a chow-diet or a 1 % sodium butyrate diet throughout pregnancy and lactation. At weaning age, samples of the maternal subcutaneous adipose tissue and offspring liver were taken. The serum indexes and expressions of proteins related to lipid metabolism were detected in the mother and offspring, respectively. The results showed that the maternal SB supplement increased the concentration of non-esterified fatty acid (NEFA) in the maternal and offspring serum (P pregnancy and lactation increased the hepatic total cholesterol (Tch) content (P pregnancy and the lactation period promotes maternal fat mobilization, which may result in fatty acid uptake and lipid accumulation in the liver of the offspring.

Human adipose-derived stem cells: definition, isolation, tissue-engineering applications.

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Nae, S; Bordeianu, I; Stăncioiu, A T; Antohi, N

2013-01-01

Recent researches have demonstrated that the most effective repair system of the body is represented by stem cells - unspecialized cells, capable of self-renewal through successive mitoses, which have also the ability to transform into different cell types through differentiation. The discovery of adult stem cells represented an important step in regenerative medicine because they no longer raises ethical or legal issues and are more accessible. Only in 2002, stem cells isolated from adipose tissue were described as multipotent stem cells. Adipose tissue stem cells benefits in tissue engineering and regenerative medicine are numerous. Development of adipose tissue engineering techniques offers a great potential in surpassing the existing limits faced by the classical approaches used in plastic and reconstructive surgery. Adipose tissue engineering clinical applications are wide and varied, including reconstructive, corrective and cosmetic procedures. Nowadays, adipose tissue engineering is a fast developing field, both in terms of fundamental researches and medical applications, addressing issues related to current clinical pathology or trauma management of soft tissue injuries in different body locations.

Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty.

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Stout, Michael B; Justice, Jamie N; Nicklas, Barbara J; Kirkland, James L

2017-01-01

Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP). These processes synergistically promote chronic sterile inflammation, insulin resistance, and lipid redistribution away from subcutaneous adipose tissue. Without intervention, these effects contribute to age-related systemic metabolic dysfunction, physical limitations, and frailty. Thus adipose tissue dysfunction may be a fundamental contributor to the elevated risk of chronic disease, disability, and adverse health outcomes with advancing age. ©2017 Int. Union Physiol. Sci./Am. Physiol. Soc.

PPAR γ is highly expressed in F4/80hi adipose tissue macrophages and dampens adipose-tissue inflammation

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Bassaganya-Riera, Josep; Misyak, Sarah; Guri, Amir J.; Hontecillas, Raquel

2009-01-01

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) γ agonist. Hence, we hypothesized that F4/80hi and F4/80lo ATM differentially express PPAR γ. This study phenotypically and functionally characterizes F4/80hi and F4/80lo ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80lo and F4/80hi ATM by quantitative real-time RT-PCR. We show that while F4/80lo macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80lo and F4/80hi ATM. Moreover, accumulation of F4/80hi ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80hi ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-α, MCP-1, and IL-10 than F4/80lo ATM. Gene expression analyses of the sorted populations revealed that only the F4/80lo population produced IL-4, whereas the F4/80hi ATM expressed greater amounts of PPAR γ, δ, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR γ in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR γ is differentially expressed in F4/80hi versus F4/80low ATM subsets and its deficiency favors a predominance of M1 markers in WAT. PMID:19423085

PPAR gamma is highly expressed in F4/80(hi) adipose tissue macrophages and dampens adipose-tissue inflammation.

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Bassaganya-Riera, Josep; Misyak, Sarah; Guri, Amir J; Hontecillas, Raquel

2009-01-01

Macrophage infiltration into adipose tissue is a hallmark of obesity. We recently reported two phenotypically distinct subsets of adipose tissue macrophages (ATM) based on the surface expression of the glycoprotein F4/80 and responsiveness to treatment with a peroxisome proliferator-activated receptor (PPAR) gamma agonist. Hence, we hypothesized that F4/80(hi) and F4/80(lo) ATM differentially express PPAR gamma. This study phenotypically and functionally characterizes F4/80(hi) and F4/80(lo) ATM subsets during obesity. Changes in gene expression were also examined on sorted F4/80(lo) and F4/80(hi) ATM by quantitative real-time RT-PCR. We show that while F4/80(lo) macrophages predominate in adipose tissue of lean mice, obesity causes accumulation of both F4/80(lo) and F4/80(hi) ATM. Moreover, accumulation of F4/80(hi) ATM in adipose tissue is associated with impaired glucose tolerance. Phenotypically, F4/80(hi) ATM express greater amounts of CD11c, MHC II, CD49b, and CX3CR1 and produce more TNF-alpha, MCP-1, and IL-10 than F4/80(lo) ATM. Gene expression analyses of the sorted populations revealed that only the F4/80(lo) population produced IL-4, whereas the F4/80(hi) ATM expressed greater amounts of PPAR gamma, delta, CD36 and toll-like receptor-4. In addition, the deficiency of PPAR gamma in immune cells favors expression of M1 and impairs M2 macrophage marker expression in adipose tissue. Thus, PPAR gamma is differentially expressed in F4/80(hi) versus F4/80(low) ATM subsets and its deficiency favors a predominance of M1 markers in WAT.

Adipose tissue and skeletal muscle blood flow during mental stress

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Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

1989-01-01

Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

Adipose tissue and skeletal muscle blood flow during mental stress

International Nuclear Information System (INIS)

Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

1989-01-01

Mental stress [a modified Stroop color word conflict test (CWT)] increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation

miRNAs in Human Subcutaneous Adipose Tissue

DEFF Research Database (Denmark)

Kristensen, Malene M.; Davidsen, Peter K.; Vigelso, Andreas

2017-01-01

Objective Obesity is central in the development of insulin resistance. However, the underlying mechanisms still need elucidation. Dysregulated microRNAs (miRNAs; post-transcriptional regulators) in adipose tissue may present an important link. Methods The miRNA expression in subcutaneous adipose ...

Insulin action in adipose tissue and muscle in hypothyroidism.

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Dimitriadis, George; Mitrou, Panayota; Lambadiari, Vaia; Boutati, Eleni; Maratou, Eirini; Panagiotakos, Demosthenes B; Koukkou, Efi; Tzanela, Marinela; Thalassinos, Nikos; Raptis, Sotirios A

2006-12-01

Although insulin resistance in thyroid hormone excess is well documented, information on insulin action in hypothyroidism is limited. To investigate this, a meal was given to 11 hypothyroid (HO; aged 45 +/- 3 yr) and 10 euthyroid subjects (EU; aged 42 +/- 4 yr). Blood was withdrawn for 360 min from veins (V) draining the anterior abdominal sc adipose tissue and the forearm and from the radial artery (A). Blood flow (BF) in adipose tissue was measured with 133Xe and in forearm with strain-gauge plethysmography. Tissue glucose uptake was calculated as (A-V)glucose(BF), lipoprotein lipase as (A-V)Triglycerides(BF), and lipolysis as [(V-A)glycerol(BF)]-lipoprotein lipase. The HO group had higher glucose and insulin levels than the EU group (P hypothyroidism: 1) glucose uptake in muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by insulin is not impaired; and 3) hypertriglyceridemia is due to decreased clearance by the adipose tissue.

Omega-3-derived mediators counteract obesity-induced adipose tissue inflammation.

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Titos, Esther; Clària, Joan

2013-12-01

Chronic low-grade inflammation in adipose tissue has been recognized as a key step in the development of obesity-associated complications. In obesity, the accumulation of infiltrating macrophages in adipose tissue and their phenotypic switch to M1-type dysregulate inflammatory adipokine production leading to obesity-linked insulin resistance. Resolvins are potent anti-inflammatory and pro-resolving mediators endogenously generated from omega-3 fatty acids that act as "stop-signals" of the inflammatory response promoting the resolution of inflammation. Recently, a deficit in the production of these endogenous anti-inflammatory signals has been demonstrated in obese adipose tissue. The restoration of their levels by either exogenous administration of these mediators or feeding omega-3-enriched diets, improves the inflammatory status of adipose tissue and ameliorates metabolic dysfunction. Here, we review the current knowledge on the role of these endogenous autacoids in the resolution of adipose tissue inflammation with special emphasis on their functional actions on macrophages. Copyright © 2013 Elsevier Inc. All rights reserved.

Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

Directory of Open Access Journals (Sweden)

Chihiro Moriya

2016-01-01

Full Text Available We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD or a 60% high-fat diet (HFD with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects.

Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

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Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

2018-02-01

Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

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Gao, Mingming; Ma, Yongjie; Liu, Dexi

2015-01-01

High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

Enantioselective gas chromatographic separation of methylsulfonyl PCBs in seal blubber, pelican muscle and human adipose tissues

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Karasek, L.; Rosmus, J. [Veterinary Institute Prague (Czech Republic). Dept. of Chemistry; Hajslova, J. [Institute of Chemical Technology (Czech Republic). Dept. of Food Chemistry and Analysis; Huehnerfuss, H. [Hamburg Univ. (Germany). Inst. fuer Organische Chemie

2004-09-15

Methyl sulfone derivatives are known to represent primary metabolic products of PCBs (MeSO2- CB) and DDE (MeSO2-DDE). These metabolites are formed via mercapturic acid pathway and belong to persistent, lipophilic compounds which accumulate in the adipose, lung, liver and kidney tissues of mammals exposed to PCBs. In 1976 Jenssen and Jansson reported the identification of PCB methyl sulfones as metabolites of PCBs in Baltic grey seal blubber. Methyl sulfones are moderately polar compounds that are only slightly less hydrophobic than the parent PCBs, and their partition coefficients fulfill the requirements for bioaccumulation. The highest concentrations have been found in kidney and lung tissues of seals, otters, beluga whales, polar bears, fishes and in human tissues. In the present investigation two samples of seal blubber, two pelican muscles and eleven human adipose tissue samples were analysed with regard to their concentrations of PCB parent compounds as well as to the respective chiral methylsulfonyl metabolites.

Evidence for the ectopic synthesis of melanin in human adipose tissue.

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Randhawa, Manpreet; Huff, Tom; Valencia, Julio C; Younossi, Zobair; Chandhoke, Vikas; Hearing, Vincent J; Baranova, Ancha

2009-03-01

Melanin is a common pigment in animals. In humans, melanin is produced in melanocytes, in retinal pigment epithelium (RPE) cells, in the inner ear, and in the central nervous system. Previously, we noted that human adipose tissue expresses several melanogenesis-related genes. In the current study, we confirmed the expression of melanogenesis-related mRNAs and proteins in human adipose tissue using real-time polymerase chain reaction and immunohistochemical staining. TYR mRNA signals were also detected by in situ hybridization in visceral adipocytes. The presence of melanin in human adipose tissue was revealed both by Fontana-Masson staining and by permanganate degradation of melanin coupled with liquid chromatography/ultraviolet/mass spectrometry determination of the pyrrole-2,3,5-tricarboxylic acid (PTCA) derivative of melanin. We also compared melanogenic activities in adipose tissues and in other human tissues using the L-[U-(14)C] tyrosine assay. A marked heterogeneity in the melanogenic activities of individual adipose tissue extracts was noted. We hypothesize that the ectopic synthesis of melanin in obese adipose may serve as a compensatory mechanism that uses its anti-inflammatory and its oxidative damage-absorbing properties. In conclusion, our study demonstrates for the first time that the melanin biosynthesis pathway is functional in adipose tissue.

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice.

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Duwaerts, Caroline C; Amin, Amin M; Siao, Kevin; Her, Chris; Fitch, Mark; Beysen, Carine; Turner, Scott M; Goodsell, Amanda; Baron, Jody L; Grenert, James P; Cho, Soo-Jin; Maher, Jacquelyn J

2017-09-01

The factors that distinguish metabolically healthy obesity from metabolically unhealthy obesity are not well understood. Diet has been implicated as a determinant of the unhealthy obesity phenotype, but which aspects of the diet induce dysmetabolism are unknown. The goal of this study was to investigate whether specific macronutrients or macronutrient combinations provoke dysmetabolism in the context of isocaloric, high-energy diets. Mice were fed 4 high-energy diets identical in calorie and nutrient content but different in nutrient composition for 3 weeks to 6 months. The test diets contained 42% carbohydrate (sucrose or starch) and 42% fat (oleate or palmitate). Weight and glucose tolerance were monitored; blood and tissues were collected for histology, gene expression, and immunophenotyping. Mice gained weight on all 4 test diets but differed significantly in other metabolic outcomes. Animals fed the starch-oleate diet developed more severe hepatic steatosis than those on other formulas. Stable isotope incorporation showed that the excess hepatic steatosis in starch-oleate-fed mice derived from exaggerated adipose tissue lipolysis. In these mice, adipose tissue lipolysis coincided with adipocyte necrosis and inflammation. Notably, the liver and adipose tissue abnormalities provoked by starch-oleate feeding were reproduced when mice were fed a mixed-nutrient Western diet with 42% carbohydrate and 42% fat. The macronutrient composition of the diet exerts a significant influence on metabolic outcome, independent of calories and nutrient proportions. Starch-oleate appears to cause hepatic steatosis by inducing progressive adipose tissue injury. Starch-oleate phenocopies the effect of a Western diet; consequently, it may provide clues to the mechanism whereby specific nutrients cause metabolically unhealthy obesity.

Critical illness induces alternative activation of M2 macrophages in adipose tissue.

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Langouche, Lies; Marques, Mirna B; Ingels, Catherine; Gunst, Jan; Derde, Sarah; Vander Perre, Sarah; D'Hoore, André; Van den Berghe, Greet

2011-01-01

We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown. We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients. Subcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels. Unlike obesity, critical illness evokes adipose tissue accumulation of alternatively activated M2

Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity*

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Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro

2013-01-01

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681

Adipose tissue engineering: state of the art, recent advances and innovative approaches.

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Tanzi, Maria Cristina; Farè, Silvia

2009-09-01

Adipose tissue is a highly specialized connective tissue found either in white or brown forms, the white form being the most abundant in adult humans. Loss or damage of white adipose tissue due to aging or pathological conditions needs reconstructive approaches. To date, two main strategies are being investigated for generating functional adipose tissue: autologous tissue/cell transplantation and adipose tissue engineering. Free-fat transplantation rarely achieves sufficient tissue augmentation owing to delayed neovascularization, with subsequent cell necrosis and graft volume shrinkage. Tissue engineering approaches represent, instead, a more suitable alternative for adipose tissue regeneration; they can be performed either with in situ or de novo adipogenesis. In situ adipogenesis or transplantation of encapsulated cells can be useful in healing small-volume defects, whereas restoration of large defects, where vascularization and a rapid volumetric gain are strict requirements, needs de novo strategies with 3D scaffold/filling matrix combinations. For adipose tissue engineering, the use of adult mesenchymal stem cells (both adipose- and bone marrow-derived stem cells) or of preadipocytes is preferred to the use of mature adipocytes, which have low expandability and poor ability for volume retention. This review intends to assemble and describe recent work on this topic, critically presenting successes obtained and drawbacks faced to date.

Epicardial adipose tissue in endocrine and metabolic diseases.

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Iacobellis, Gianluca

2014-05-01

Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

Epicardial Adipose Tissue Thickness in Patients With Subclinical Hypothyroidism and the Relationship Thereof With Visceral Adipose Tissue Thickness.

Science.gov (United States)

Arpaci, Dilek; Gurkan Tocoglu, Aysel; Yilmaz, Sabiye; Korkmaz, Sumeyye; Ergenc, Hasan; Gunduz, Huseyin; Keser, Nurgul; Tamer, Ali

2016-03-01

Subclinical hypothyroidism (SH) is associated with cardiovascular metabolic syndromes, especially dislipidemia and abdominal obesity. Visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) have the same ontogenic origin and produce many proinflammatory and proatherogenic cytokines. We evaluated EAT and VAAT thickness in patients with SH. Forty-one patients with SH and 35 controls were included in the study. Demographical and anthropometric features of both patients and controls were recorded. Thyroid and metabolic parameters were measured. EAT was measured using 2D-transthoracic echocardiography. The age and gender distributions were similar in the two groups (P = 0.998 and P = 0.121, respectively). Body mass index (BMI), fat mass, waist circumference (WC), hip circumference (HC), the WC/HC ratio, and the thicknesses of VAAT and abdominal subcutaneous adipose tissue were higher in the case group than the control group (all P values 0.05). We found no difference between the two groups in fasting plasma glucose (FPG) level (P = 0.780), but the levels of LDL-C and TG differed significantly (P = 0.002 and P = 0.026, respectively). The serum TSH level was higher and the FT4 level was lower in the case than the control group (both P values <0.01). Increased abdominal adipose tissue thickness in patients with SH is associated with atherosclerosis. To detemine the risk of atherosclerosis in such patients, EAT measurements are valuable; such assessment is simple to perform.

Mechanically robust cryogels with injectability and bioprinting supportability for adipose tissue engineering.

Science.gov (United States)

Qi, Dianjun; Wu, Shaohua; Kuss, Mitchell A; Shi, Wen; Chung, Soonkyu; Deegan, Paul T; Kamenskiy, Alexey; He, Yini; Duan, Bin

2018-05-26

Bioengineered adipose tissues have gained increased interest as a promising alternative to autologous tissue flaps and synthetic adipose fillers for soft tissue augmentation and defect reconstruction in clinic. Although many scaffolding materials and biofabrication methods have been investigated for adipose tissue engineering in the last decades, there are still challenges to recapitulate the appropriate adipose tissue microenvironment, maintain volume stability, and induce vascularization to achieve long-term function and integration. In the present research, we fabricated cryogels consisting of methacrylated gelatin, methacrylated hyaluronic acid, and 4arm poly(ethylene glycol) acrylate (PEG-4A) by using cryopolymerization. The cryogels were repeatedly injectable and stretchable, and the addition of PEG-4A improved the robustness and mechanical properties. The cryogels supported human adipose progenitor cell (HWA) and adipose derived mesenchymal stromal cell adhesion, proliferation, and adipogenic differentiation and maturation, regardless of the addition of PEG-4A. The HWA laden cryogels facilitated the co-culture of human umbilical vein endothelial cells (HUVEC) and capillary-like network formation, which in return also promoted adipogenesis. We further combined cryogels with 3D bioprinting to generate handleable adipose constructs with clinically relevant size. 3D bioprinting enabled the deposition of multiple bioinks onto the cryogels. The bioprinted flap-like constructs had an integrated structure without delamination and supported vascularization. Adipose tissue engineering is promising for reconstruction of soft tissue defects, and also challenging for restoring and maintaining soft tissue volume and shape, and achieving vascularization and integration. In this study, we fabricated cryogels with mechanical robustness, injectability, and stretchability by using cryopolymerization. The cryogels promoted cell adhesion, proliferation, and adipogenic

Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

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Wen Liang

Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

Maternal nutritional manipulations program adipose tissue dysfunction in offspring

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Simon eLecoutre

2015-05-01

Full Text Available Based on the concept of Developmental Origin of Health and Disease, both human and animal studies have demonstrated a close link between nutrient supply perturbations in the fetus or neonate (i.e., maternal undernutrition, obesity, gestational diabetes and/or rapid catch-up growth and increased risk of adult-onset obesity. Indeed, the adipose tissue has been recognized as a key target of developmental programming in a sex-and depot-specific manner. Despite different developmental time windows, similar mechanisms of adipose tissue programming have been described in rodents and in bigger mammals (sheep, primates. Maternal nutritional manipulations reprogram offspring’s adipose tissue resulting in series of alterations: enhanced adipogenesis and lipogenesis, impaired sympathetic activity with reduced noradrenergic innervations and thermogenesis as well as low-grade inflammation. These changes affect adipose tissue development, distribution and composition predisposing offspring to fat accumulation. Modifications of hormonal tissue sensitivity (i.e., leptin, insulin, glucocorticoids and/or epigenetic mechanisms leading to persistent changes in gene expression may account for long-lasting programming across generations.

CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis

NARCIS (Netherlands)

Park, Jong-Gil; Xu, Xu; Cho, Sungyun; Hur, Kyu Yeon; Lee, Myung-Shik; Kersten, Sander; Lee, Ann-Hwee

2016-01-01

Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG

Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels*

OpenAIRE

Herman, Mark A.; She, Pengxiang; Peroni, Odile D.; Lynch, Christopher J.; Kahn, Barbara B.

2010-01-01

Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent obse...

Adipose tissue transcriptome changes during obesity development in female dogs.

Science.gov (United States)

Grant, Ryan W; Vester Boler, Brittany M; Ridge, Tonya K; Graves, Thomas K; Swanson, Kelly S

2011-03-29

During the development of obesity, adipose tissue undergoes major expansion and remodeling, but the biological processes involved in this transition are not well understood. The objective of this study was to analyze global gene expression profiles of adipose tissue in dogs, fed a high-fat diet, during the transition from a lean to obese phenotype. Nine female beagles (4.09 ± 0.64 yr; 8.48 ± 0.35 kg) were randomized to ad libitum feeding or body weight maintenance. Subcutaneous adipose tissue biopsy, blood, and dual x-ray absorptiometry measurements were collected at 0, 4, 8, 12, and 24 wk of feeding. Serum was analyzed for glucose, insulin, fructosamine, triglycerides, free fatty acids, adiponectin, and leptin. Formalin-fixed adipose tissue was used for determination of adipocyte size. Adipose RNA samples were hybridized to Affymetrix Canine 2.0 microarrays. Statistical analysis, using repeated-measures ANOVA, showed ad libitum feeding increased (P obesity development.

Novel GLP-1 Analog Supaglutide Reduces HFD-Induced Obesity Associated with Increased Ucp-1 in White Adipose Tissue in Mice

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Yun Wan

2017-05-01

Full Text Available GLP-1, an important incretin hormone plays an important role in the regulation of glucose homeostasis. However, the therapeutic use of native GLP-1 is limited due to its short half-life. We recently developed a novel GLP-1 mimetics (supaglutide by genetically engineering recombinant fusion protein production techniques. We demonstrated that this formulation possessed long-lasting GLP-1 actions and was effective in glycemic control in both type 1 and type 2 diabetes rodent models. Here, we investigated the effects of supaglutide in regulating energy homeostasis in obese mice. Mice were fed with high-fat diet (HFD for 6 months to induce obesity and then subjected to supaglutide treatment (300 μg/kg, bi-weekly for 4 weeks, and placebo as control. Metabolic conditions were monitored and energy expenditure was assessed by indirect calorimetry (CLAMS. Cold tolerance test was performed to evaluate brown-adipose tissue (BAT activities in response to cold challenge. Glucose tolerance and insulin resistance were evaluated by intraperitoneal glucose tolerance test and insulin tolerance tests. Liver and adipose tissues were collected for histology analysis. Expression of uncoupling protein 1(Ucp1 in adipose tissues was evaluated by Western blotting. We found that supaglutide treatment reduced body weight, which was associated with reduced food intake. Compared to the placebo control, supaglutide treatment improved lipid profile, i.e., significantly decreased circulating total cholesterol levels, declined serum triglyceride, and free fatty acid levels. Importantly, the intervention significantly reduced fatty liver, decreased liver triglyceride content, and concomitantly ameliorated liver injury exemplified by declined hepatic alanine aminotransferase (ALT and aspartic transaminase (AST content. Remarkably, supaglutide reduced hepatic lipid accumulation and altered morphometry in favor of small adipocytes in fat. This is consistent with the observation that

Generating an Engineered Adipose Tissue Flap Using an External Suspension Device.

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Wan, Jinlin; Dong, Ziqing; Lei, Chen; Lu, Feng

2016-07-01

The tissue-engineering chamber technique can generate large volumes of adipose tissue, which provides a potential solution for the complex reconstruction of large soft-tissue defects. However, major drawbacks of this technique are the foreign-body reaction and the volume limitation imposed by the chamber. In this study, the authors developed a novel tissue-engineering method using a specially designed external suspension device that generates an optimized volume of adipose flap and avoids the implantation of foreign material. The rabbits were processed using two different tissue-engineering methods, the external suspension device technique and the traditional tissue-engineering chamber technique. The adipose flaps generated by the external suspension device had a normal adipose tissue structure that was as good as that generated by the traditional tissue-engineering chamber, but the flap volume was much larger. The final volume of the engineered adipose flap grew between weeks 0 and 36 from 5.1 ml to 30.7 ml in the traditional tissue-engineering chamber group and to 80.5 ml in the external suspension device group. During the generation process, there were no marked differences between the two methods in terms of structural and cellular changes of the flap, except that the flaps in the traditional tissue-engineering chamber group had a thicker capsule at the early stage. In addition, the enlarged flaps generated by the external suspension device could be reshaped into specific shapes by the implant chamber. This minimally invasive external suspension device technique can generate large-volume adipose flaps. Combined with a reshaping method, this technique should facilitate clinical application of adipose tissue engineering.

Prolactin suppresses malonyl-CoA concentration in human adipose tissue

DEFF Research Database (Denmark)

Nilsson, L. A.; Roepstorff, Carsten; Kiens, Bente

2009-01-01

Prolactin is best known for its involvement in lactation, where it regulates mechanisms that supply nutrients for milk production. In individuals with pathological hyperprolactinemia, glucose and fat homeostasis have been reported to be negatively influenced. It is not previously known, however......, whether prolactin regulates lipogenesis in human adipose tissue. The aim of this study was to investigate the effect of prolactin on lipogenesis in human adipose tissue in vitro. Prolactin decreased the concentration of malonyl-CoA, the product of the first committed step in lipogenesis, to 77......+/-6% compared to control 100+/-5% (p=0.022) in cultured human adipose tissue. In addition, prolactin was found to decrease glucose transporter 4 ( GLUT4) mRNA expression, which may cause decreased glucose uptake. In conclusion, we propose that prolactin decreases lipogenesis in human adipose tissue...

Identification of a cytochrome P4502E1/Bid/C1q-dependent axis mediating inflammation in adipose tissue after chronic ethanol feeding to mice.

Science.gov (United States)

Sebastian, Becky M; Roychowdhury, Sanjoy; Tang, Hui; Hillian, Antoinette D; Feldstein, Ariel E; Stahl, Gregory L; Takahashi, Kazue; Nagy, Laura E

2011-10-14

Chronic, heavy alcohol exposure results in inflammation in adipose tissue, insulin resistance, and liver injury. Here we have identified a CYP2E1/Bid/C1q-dependent pathway that is activated in response to chronic ethanol and is required for the development of inflammation in adipose tissue. Ethanol feeding for 25 days to wild-type (C57BL/6J) mice increased expression of multiple markers of adipose tissue inflammation relative to pair-fed controls independent of increased body weight or adipocyte size. Ethanol feeding increased the expression of CYP2E1 in adipocytes, but not stromal vascular cells, in adipose tissue and Cyp2e1(-/-) mice were protected from adipose tissue inflammation in response to ethanol. Ethanol feeding also increased the number of TUNEL-positive nuclei in adipose tissue of wild-type mice but not in Cyp2e1(-/-) or Bid (-/-) mice. Apoptosis contributed to adipose inflammation, as the expression of multiple inflammatory markers was decreased in mice lacking the Bid-dependent apoptotic pathway. The complement protein C1q binds to apoptotic cells, facilitating their clearance and activating complement. Making use of C1q-deficient mice, we found that activation of complement via C1q provided the critical link between CYP2E1/Bid-dependent apoptosis and onset of adipose tissue inflammation in response to chronic ethanol. In summary, chronic ethanol increases CYP2E1 activity in adipose, leading to Bid-mediated apoptosis and activation of complement via C1q, finally resulting in adipose tissue inflammation. Taken together, these data identify a novel mechanism for the development of adipose tissue inflammation that likely contributes to the pathophysiological effects of ethanol.

Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice

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Michael J. Haley

2017-10-01

Full Text Available Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids. Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.

PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism.

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Gema Medina-Gomez

2007-04-01

Full Text Available Peroxisome proliferator activated receptor gamma 2 (PPARg2 is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2(-/- Lep(ob/Lep(ob (POKO mouse, resulted in decreased fat mass, severe insulin resistance, beta-cell failure, and dyslipidaemia. Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species. Our data also indicate that PPARg2 may be required for the beta-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a promoting adipose tissue expansion, (b increasing the lipid-buffering capacity of peripheral organs, and (c facilitating the adaptive proliferative response of beta-cells to insulin resistance.

Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to diet-induced obesity and glucose intolerance in mice that lack PKA regulatory subunit type IIα.

Science.gov (United States)

London, Edra; Nesterova, Maria; Sinaii, Ninet; Szarek, Eva; Chanturiya, Tatyana; Mastroyannis, Spyridon A; Gavrilova, Oksana; Stratakis, Constantine A

2014-09-01

The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cβ resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIα subunit in mice (RIIαKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIαKO mice. Additionally, RIIα deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIα represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease.

High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

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Mingming Gao

Full Text Available High-fat diet (HFD has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

Polychlorinated naphthalenes in human adipose tissue from New York, USA

International Nuclear Information System (INIS)

Kunisue, Tatsuya; Johnson-Restrepo, Boris; Hilker, David R.; Aldous, Kenneth M.; Kannan, Kurunthachalam

2009-01-01

Polychlorinated naphthalenes (PCNs) are persistent, bioaccumulative, and toxic contaminants. Prior to this study, the occurrence of PCNs in human adipose tissues from the USA has not been analyzed. Here, we have measured concentrations of PCNs in human adipose tissue samples collected in New York City during 2003-2005. Concentrations of PCNs were in the range of 61-2500 pg/g lipid wt. in males and 21-910 pg/g lipid wt. in females. PCN congeners 52/60 (1,2,3,5,7/1,2,4,6,7) and 66/67 (1,2,3,4,6,7/1,2,3,5,6,7) were predominant, collectively accounting for 66% of the total PCN concentrations. Concentrations of PCNs in human adipose tissues were 2-3 orders of magnitude lower than the previously reported concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Concentrations of PCNs were not correlated with PCB concentrations. The contribution of PCNs to dioxin-like toxic equivalents (TEQs) in human adipose tissues was estimated to be <1% of the polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/F)-TEQs. - Polychlorinated naphthalenes have been measured in human adipose tissues from the USA for the first time

Adipose tissue in muscle: a novel depot similar in size to visceral adipose tissue

NARCIS (Netherlands)

Gallagher, D.; Kuznia, P.; Heshka, S.; Albu, J.; Heymsfield, S.B.; Goodpaster, B.H.; Visser, M.; Harris, T.B.

2005-01-01

BACKGROUND: The manner in which fat depot volumes and distributions, particularly the adipose tissue (AT) between the muscles, vary by race is unknown. OBJECTIVE: The objective was to quantify a previously unstudied and novel intermuscular AT (IMAT) depot and subcutaneous AT, visceral AT (VAT), and

Differential Expression of , , and Genes in Various Adipose Tissues and Muscle from Yanbian Yellow Cattle and Yan Yellow Cattle

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Shuang Ji

2014-01-01

Full Text Available The objective of this study was to investigate the correlation between cattle breeds and deposit of adipose tissues in different positions and the gene expressions of peroxisome proliferator-activated receptor gamma (PPARγ, fatty acid synthase (FASN, and Acyl-CoA dehydrogenase (ACADM, which are associated with lipid metabolism and are valuable for understanding the physiology in fat depot and meat quality. Yanbian yellow cattle and Yan yellow cattle reared under the same conditions display different fat proportions in the carcass. To understand this difference, the expression of PPARγ, FASN, and ACADM in different adipose tissues and longissimus dorsi muscle (LD in these two breeds were analyzed using the Real-time quantitative polymerase chain reaction method (qRT-PCR. The result showed that PPARγ gene expression was significantly higher in adipose tissue than in LD in both breeds. PPARγ expression was also higher in abdominal fat, in perirenal fat than in the subcutaneous fat (p<0.05 in Yanbian yellow cattle, and was significantly higher in subcutaneous fat in Yan yellow cattle than that in Yanbian yellow cattle. On the other hand, FASN mRNA expression levels in subcutaneous fat and abdominal fat in Yan yellow cattle were significantly higher than that in Yanbian yellow cattle. Interestingly, ACADM gene shows greater fold changes in LD than in adipose tissues in Yan yellow cattle. Furthermore, the expressions of these three genes in lung, colon, kidney, liver and heart of Yanbian yellow cattle and Yan yellow cattle were also investigated. The results showed that the highest expression levels of PPARγ and FASN genes were detected in the lung in both breeds. The expression of ACADM gene in kidney and liver were higher than that in other organs in Yanbian yellow cattle, the comparison was not statistically significant in Yan yellow cattle.

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Biomarkers of Habitual Fish Intake in Adipose-Tissue

DEFF Research Database (Denmark)

Marckmann, P.; Lassen, Anne Dahl; Haraldsdottir, H.

1995-01-01

The association between habitual fish and marine n-3 polyunsaturated fatty acid (PUFA) intake, and the fatty acid composition of subcutaneous fat was studied in 24 healthy young volunteers. Habitual dietary intakes were estimated from three 7-d weighed food records made at months 0, 5, and 8...... of the 8-mo study period. The adipose tissue fatty acid composition of each individual was determined by gas chromatography as the mean of two gluteal biopsies, obtained in the first and the last month of the study. The daily consumption of fish and of marine n-3 PUFAs in absolute terms (g....../d) was significantly associated with adipose tissue docosahexaenoic acid content (DHA; r = 0.55 and 0.58, respectively, P acid contents. Our study indicates that the adipose tissue DHA content is the biomarker of choice for the assessment of long...

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File list: DNS.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: DNS.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Adp.50.AllAg.Adipose_Tissue,_White hg19 DNase-seq Adipocyte Adipose Tissue, Whi...te http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.50.AllAg.Adipose_Tissue,_White.bed ...

File list: DNS.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Adp.20.AllAg.Adipose_Tissue,_White hg19 DNase-seq Adipocyte Adipose Tissue, Whi...te http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.20.AllAg.Adipose_Tissue,_White.bed ...

Adipose tissue content and distribution in children and adolescents with bronchial asthma.

Science.gov (United States)

Umławska, Wioleta

2015-02-01

The excess of adipose tissue and the pattern of adipose tissue distribution in the body seem to play an important role in the complicated dependencies between obesity and risk of developing asthma. The aim of the present study was to determine nutritional status in children and adolescents with bronchial asthma with special emphasis on adipose tissue distribution evaluated on the basis of skin-fold thicknesses, and to determine the relationships between patterns of adipose tissue distribution and the course of the disease. Anthropometric data on height, weight, circumferences and skin-fold thicknesses were extracted from the medical histories of 261 children diagnosed with asthma bronchitis. Values for children with asthma were compared to Polish national growth reference charts. Distribution of subcutaneous adipose tissue was evaluated using principal components analysis (PCA). Multivariate linear regression analyses tested the effect of three factors on subcutaneous adipose tissue distribution: type of asthma, the severity of the disease and the duration of the disease. Mean body height in the children examined in this study was lower than in their healthy peers. Mean BMI and skin-fold thicknesses were significantly higher and lean body mass was lower in the study group. Excess body fat was noted, especially in girls. Adipose tissue was preferentially deposited in the trunk in girls with severe asthma, as well as in those who had been suffering from asthma for a longer time. The type of asthma, atopic or non-atopic, had no observable effect on subcutaneous adipose tissue distribution in children examined. The data suggest that long-treated subjects and those with severe bronchial asthma accumulate more adipose tissue on the trunk. It is important to regularly monitor nutritional status in children with asthma, especially in those receiving high doses of systemic or inhaled glucocorticosteroids, and long-term treatment as well. Copyright © 2014 Elsevier Ltd. All

Myocardial regeneration potential of adipose tissue-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

2010-10-22

Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

Myocardial regeneration potential of adipose tissue-derived stem cells

International Nuclear Information System (INIS)

Bai, Xiaowen; Alt, Eckhard

2010-01-01

Research highlights: → Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. → For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. → This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying

File list: NoD.Adp.50.AllAg.Adipose_Tissue [Chip-atlas[Archive

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

Full Text Available NoD.Adp.05.AllAg.Adipose_Tissue hg19 No description Adipocyte Adipose Tissue SRX134...732 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Adp.05.AllAg.Adipose_Tissue.bed ...

Tributyltin chloride leads to adiposity and impairs metabolic functions in the rat liver and pancreas.

Science.gov (United States)

Bertuloso, Bruno D; Podratz, Priscila L; Merlo, Eduardo; de Araújo, Julia F P; Lima, Leandro C F; de Miguel, Emilio C; de Souza, Leticia N; Gava, Agata L; de Oliveira, Miriane; Miranda-Alves, Leandro; Carneiro, Maria T W D; Nogueira, Celia R; Graceli, Jones B

2015-05-19

Tributyltin chloride (TBT) is an environmental contaminant used in antifouling paints of boats. Endocrine disruptor effects of TBT are well established in animal models. However, the adverse effects on metabolism are less well understood. The toxicity of TBT in the white adipose tissue (WAT), liver and pancreas of female rats were assessed. Animals were divided into control and TBT (0.1 μg/kg/day) groups. TBT induced an increase in the body weight of the rats by the 15th day of oral exposure. The weight gain was associated with high parametrial (PR) and retroperitoneal (RP) WAT weights. TBT-treatment increased the adiposity, inflammation and expression of ERα and PPARγ proteins in both RP and PR WAT. In 3T3-L1 cells, estrogen treatment reduced lipid droplets accumulation, however increased the ERα protein expression. In contrast, TBT-treatment increased the lipid accumulation and reduced the ERα expression. WAT metabolic changes led to hepatic inflammation, lipid accumulation, increase of PPARγ and reduction of ERα protein expression. Accordingly, there were increases in the glucose tolerance and insulin sensitivity tests with increases in the number of pancreatic islets and insulin levels. These findings suggest that TBT leads to adiposity in WAT specifically, impairing the metabolic functions of the liver and pancreas. Copyright © 2015. Published by Elsevier Ireland Ltd.

White adipose tissue: Getting nervous

NARCIS (Netherlands)

Fliers, E.; Kreier, F.; Voshol, P. J.; Havekes, L. M.; Sauerwein, H. P.; Kalsbeek, A.; Buijs, R. M.; Romijn, J. A.

2003-01-01

Neuroendocrine research has altered the traditional perspective of white adipose tissue (WAT) as a passive store of triglycerides. In addition to fatty acids, WAT produces many hormones and can therefore be designated as a traditional endocrine gland actively participating in the integrative

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease.

Science.gov (United States)

Petta, S; Amato, M C; Di Marco, V; Cammà, C; Pizzolanti, G; Barcellona, M R; Cabibi, D; Galluzzo, A; Sinagra, D; Giordano, C; Craxì, A

2012-01-01

Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. Serum levels of TNFα, IL-6, adiponectin and leptin were also assessed. All biopsies were scored for NAFLD activity score (NAS) and its components, and for staging (Kleiner). By multiple linear regression analysis, VAI was independently associated with higher HOMA (P = 0.04), and fibrosis (P = 0.04). In addition, an independent association was found between higher VAI and lower adiponectin levels (P = 0.002). Higher HOMA (OR 1.149, 95% CI 1.003-1.316, P = 0.04), higher VAI (OR 1.446, 95% CI 1.023-2.043, P = 0.03), lobular inflammation (OR 3.777, 95% CI 1.771-8.051, P = 0.001), and ballooning (OR 2.884, 95% CI 1.231-6.757, P = 0.01) were correlated with significant fibrosis (F2-F4) on multiple logistic regression analysis. In particular, the prevalence of significant fibrosis progressively increased from patients with a VAI ≤ 2.1 and HOMA ≤ 3.4 (26%) to those with a VAI > 2.1 and HOMA > 3.4 (83%). In NAFLD patients, visceral adiposity index is an expression of both qualitative and quantitative adipose tissue dysfunction and, together with insulin resistance, is independently correlated with significant fibrosis. © 2011 Blackwell Publishing Ltd.

Browning of Subcutaneous White Adipose Tissue in Humans

OpenAIRE

Sidossis, Labros S.; Porter, Craig; Saraf, Manish K.; Børsheim, Elisabet; Radhakrishnan, Ravi S.; Chao, Tony; Ali, Arham; Chondronikola, Maria; Mlcak, Ronald; Finnerty, Celeste C.; Hawkins, Hal K.; Toliver-Kinsky, Tracy; Herndon, David N.

2015-01-01

Since the presence of brown adipose tissue (BAT) was confirmed in adult humans, BAT has become a therapeutic target for obesity and insulin resistance. We examined whether human subcutaneous white adipose tissue (sWAT) can adopt a BAT-like phenotype using a clinical model of prolonged and severe adrenergic stress. sWAT samples were collected from severely burned and healthy individuals. A subset of burn victims were prospectively followed during their acute hospitalization. Browning of sWAT w...

Differential patterns of serum concentration and adipose tissue expression of chemerin in obesity: adipose depot specificity and gender dimorphism.

Science.gov (United States)

Alfadda, Assim A; Sallam, Reem M; Chishti, Muhammad Azhar; Moustafa, Amr S; Fatma, Sumbul; Alomaim, Waleed S; Al-Naami, Mohammed Y; Bassas, Abdulelah F; Chrousos, George P; Jo, Hyunsun

2012-06-01

Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentiation and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity.

Intrinsic regulation of blood flow in adipose tissue

DEFF Research Database (Denmark)

Henriksen, O; Nielsen, Steen Levin; Paaske, W

1976-01-01

Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called autoregulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated...... subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an autoregulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g-min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue...... vasoconstriction with pronounced flow reduction. These two reactions may be important for local regulation of blood flow in subcutaneous tissue during orthostatic changes in arterial and venous pressure. It is concluded that the response in adipose tissue to changes in arterial pressure (autoregulation), venous...

Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

DEFF Research Database (Denmark)

Basse, Astrid L.; Dixen, Karen; Yadav, Rachita

2015-01-01

. Conclusions: Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides...... NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time...

Novel Role of Endogenous Catalase in Macrophage Polarization in Adipose Tissue.

Science.gov (United States)

Park, Ye Seul; Uddin, Md Jamal; Piao, Lingjuan; Hwang, Inah; Lee, Jung Hwa; Ha, Hunjoo

2016-01-01

Macrophages are important components of adipose tissue inflammation, which results in metabolic diseases such as insulin resistance. Notably, obesity induces a proinflammatory phenotypic switch in adipose tissue macrophages, and oxidative stress facilitates this switch. Thus, we examined the role of endogenous catalase, a key regulator of oxidative stress, in the activity of adipose tissue macrophages in obese mice. Catalase knockout (CKO) exacerbated insulin resistance, amplified oxidative stress, and accelerated macrophage infiltration into epididymal white adipose tissue in mice on normal or high-fat diet. Interestingly, catalase deficiency also enhanced classical macrophage activation (M1) and inflammation but suppressed alternative activation (M2) regardless of diet. Similarly, pharmacological inhibition of catalase activity using 3-aminotriazole induced the same phenotypic switch and inflammatory response in RAW264.7 macrophages. Finally, the same phenotypic switch and inflammatory responses were observed in primary bone marrow-derived macrophages from CKO mice. Taken together, the data indicate that endogenous catalase regulates the polarization of adipose tissue macrophages and thereby inhibits inflammation and insulin resistance.

Innate immunity orchestrates adipose tissue homeostasis.

Science.gov (United States)

Lin, Yi-Wei; Wei, Li-Na

2017-06-23

Obesity is strongly associated with multiple diseases including insulin resistance, type 2 diabetes, cardiovascular diseases, fatty liver disease, neurodegenerative diseases and cancers, etc. Adipose tissue (AT), mainly brown AT (BAT) and white AT (WAT), is an important metabolic and endocrine organ that maintains whole-body homeostasis. BAT contributes to non-shivering thermogenesis in a cold environment; WAT stores energy and produces adipokines that fine-tune metabolic and inflammatory responses. Obesity is often characterized by over-expansion and inflammation of WAT where inflammatory cells/mediators are abundant, especially pro-inflammatory (M1) macrophages, resulting in chronic low-grade inflammation and leading to insulin resistance and metabolic complications. Macrophages constitute the major component of innate immunity and can be activated as a M1 or M2 (anti-inflammatory) phenotype in response to environmental stimuli. Polarized M1 macrophage causes AT inflammation, whereas polarized M2 macrophage promotes WAT remodeling into the BAT phenotype, also known as WAT browning/beiging, which enhances insulin sensitivity and metabolic health. This review will discuss the regulation of AT homeostasis in relation to innate immunity.

Central melanin-concentrating hormone influences liver and adipose metabolism via specific hypothalamic nuclei and efferent autonomic/JNK1 pathways.

Science.gov (United States)

Imbernon, Monica; Beiroa, Daniel; Vázquez, María J; Morgan, Donald A; Veyrat-Durebex, Christelle; Porteiro, Begoña; Díaz-Arteaga, Adenis; Senra, Ana; Busquets, Silvia; Velásquez, Douglas A; Al-Massadi, Omar; Varela, Luis; Gándara, Marina; López-Soriano, Francisco-Javier; Gallego, Rosalía; Seoane, Luisa M; Argiles, Josep M; López, Miguel; Davis, Roger J; Sabio, Guadalupe; Rohner-Jeanrenaud, Françoise; Rahmouni, Kamal; Dieguez, Carlos; Nogueiras, Ruben

2013-03-01

Specific neuronal circuits modulate autonomic outflow to liver and white adipose tissue. Melanin-concentrating hormone (MCH)-deficient mice are hypophagic, lean, and do not develop hepatosteatosis when fed a high-fat diet. Herein, we sought to investigate the role of MCH, an orexigenic neuropeptide specifically expressed in the lateral hypothalamic area, on hepatic and adipocyte metabolism. Chronic central administration of MCH and adenoviral vectors increasing MCH signaling were performed in rats and mice. Vagal denervation was performed to assess its effect on liver metabolism. The peripheral effects on lipid metabolism were assessed by real-time polymerase chain reaction and Western blot. We showed that the activation of MCH receptors promotes nonalcoholic fatty liver disease through the parasympathetic nervous system, whereas it increases fat deposition in white adipose tissue via the suppression of sympathetic traffic. These metabolic actions are independent of parallel changes in food intake and energy expenditure. In the liver, MCH triggers lipid accumulation and lipid uptake, with c-Jun N-terminal kinase being an essential player, whereas in adipocytes MCH induces metabolic pathways that promote lipid storage and decreases lipid mobilization. Genetic activation of MCH receptors or infusion of MCH specifically in the lateral hypothalamic area modulated hepatic lipid metabolism, whereas the specific activation of this receptor in the arcuate nucleus affected adipocyte metabolism. Our findings show that central MCH directly controls hepatic and adipocyte metabolism through different pathways. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Impact of training state on fasting-induced regulation of adipose tissue metabolism in humans

DEFF Research Database (Denmark)

Bertholdt, Lærke; Gudiksen, Anders; Stankiewicz, Tomasz

2018-01-01

Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study was to investig......Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study...... was to investigate 1) fasting-induced regulation of lipolysis and glyceroneogenesis in human adipose tissue as well as 2) the impact of training state on basal oxidative capacity and fasting-induced metabolic regulation in human adipose tissue. Untrained (VO2max 55ml......RNA content were higher in trained subjects than untrained subjects. In addition, trained subjects had higher adipose tissue hormone sensitive lipase Ser660 phosphorylation and adipose triglyceride lipase protein content as well as higher plasma free fatty acids concentration than untrained subjects during...

Hepatic and visceral adipose tissue 11βHSD1 expressions are markers of body weight loss after bariatric surgery.

Science.gov (United States)

Pardina, Eva; Baena-Fustegueras, Juan Antonio; Fort, José Manuel; Ferrer, Roser; Rossell, Joana; Esteve, Montserrat; Peinado-Onsurbe, Julia; Grasa, Mar

2015-09-01

Cortisolemia and 11βHSD1 in liver and adipose tissue are altered in obesity. However, their participation in the development of obesity remains unclear. This study analyzed these parameters in the transition from morbid to type 1 obesity after bariatric surgery. A group of 34 patients with morbid obesity and 22 nonobese subjects were recruited. Initial hypothalamus-pituitary-adrenal (HPA) basal activity and 11βHSD1 mRNA expression in liver, subcutaneous (SAT), and visceral adipose tissue (VAT) were evaluated. A year after bariatric surgery (weight loss of 48 kg), these parameters were reappraised in plasma, SAT, and liver. Body weight loss was accompanied by a downshift in basal HPA activity and 11βHSD1 expression in SAT. In patients with morbid obesity, 11βHSD1 expression correlated positively with BMI in VAT and negatively in liver at 6 and 12 months after surgery. In SAT, a correlation was observed with body weight only when patients showed type 1 obesity. Insulin, glucose, and HOMA correlated positively with all the HPA indicators and 11βHSD1 expression in SAT. Body weight loss after bariatric surgery is accompanied by a downshift in basal HPA activity. Hepatic and VAT 11βHSD1 expressions in morbid obesity are predictors of body weight loss. © 2015 The Obesity Society.

Early Overfeed-Induced Obesity Leads to Brown Adipose Tissue Hypoactivity in Rats

Directory of Open Access Journals (Sweden)

Douglas L. de Almeida

2013-12-01

Full Text Available Background/Aims: Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Methods: Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups and small (3 pups litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Results: Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C and dark (NL 38°C vs. SL 37.6°C periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (pConclusion: Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults.

Periodontitis contributes to adipose tissue inflammation through the NF-B, JNK and ERK pathways to promote insulin resistance in a rat model.

Science.gov (United States)

Huang, Yanli; Zeng, Jin; Chen, Guoqing; Xie, Xudong; Guo, Weihua; Tian, Weidong

2016-12-01

This study aimed to investigate the mechanism by which periodontitis affects the inflammatory response and systemic insulin resistance in the white adipose and liver tissues in an obese rat model. The obese model was generated by feeding rats a high fat diet. The periodontitis model was induced by ligatures and injection of "red complex", which consisted of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, for two weeks. When compared with rats without periodontitis, fasting glucose levels and homeostasis model assessment index were significantly increased in rats with periodontitis, suggesting that periodontitis promotes the development of insulin resistance in obese rats. Gene and protein expression analysis in white adipose and liver tissue revealed that experimental periodontitis stimulated the expression of inflammatory cytokines, such as tumor necrosis factors-alpha, interleukin-1 beta, toll-like receptor 2 and toll-like receptor 4. Signals associated with inflammation and insulin resistance, including nuclear factor- B, c-Jun amino-terminal kinase and extracellular-signal regulated kinase were significantly activated in the white adipose tissue from obese rats with periodontitis compared to obese rats without periodontitis. Taken together, these findings suggest that periodontitis plays an important role in aggravating the development of local white adipose inflammation and systemic insulin resistance in rat models. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Abalation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues

Science.gov (United States)

Aging is associated with increased adiposity in white adipose tissues and impaired thermogenesis in brown adipose tissues; both contribute to increased incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating orexigenic hormone that promotes adiposity. In this study, we show ...

Cell supermarket: Adipose tissue as a source of stem cells

Science.gov (United States)

Adipose tissue is derived from numerous sources, and in recent years has been shown to provide numerous cells from what seemingly was a population of homogeneous adipocytes. Considering the types of cells that adipose tissue-derived cells may form, these cells may be useful in a variety of clinical ...

Development of the mouse dermal adipose layer occurs independently of subcutaneous adipose tissue and is marked by restricted early expression of FABP4.

Directory of Open Access Journals (Sweden)

Kamila Wojciechowicz

Full Text Available The laboratory mouse is a key animal model for studies of adipose biology, metabolism and disease, yet the developmental changes that occur in tissues and cells that become the adipose layer in mouse skin have received little attention. Moreover, the terminology around this adipose body is often confusing, as frequently no distinction is made between adipose tissue within the skin, and so called subcutaneous fat. Here adipocyte development in mouse dorsal skin was investigated from before birth to the end of the first hair follicle growth cycle. Using Oil Red O staining, immunohistochemistry, quantitative RT-PCR and TUNEL staining we confirmed previous observations of a close spatio-temporal link between hair follicle development and the process of adipogenesis. However, unlike previous studies, we observed that the skin adipose layer was created from cells within the lower dermis. By day 16 of embryonic development (e16 the lower dermis was demarcated from the upper dermal layer, and commitment to adipogenesis in the lower dermis was signalled by expression of FABP4, a marker of adipocyte differentiation. In mature mice the skin adipose layer is separated from underlying subcutaneous adipose tissue by the panniculus carnosus. We observed that the skin adipose tissue did not combine or intermix with subcutaneous adipose tissue at any developmental time point. By transplanting skin isolated from e14.5 mice (prior to the start of adipogenesis, under the kidney capsule of adult mice, we showed that skin adipose tissue develops independently and without influence from subcutaneous depots. This study has reinforced the developmental link between hair follicles and skin adipocyte biology. We argue that because skin adipocytes develop from cells within the dermis and independently from subcutaneous adipose tissue, that it is accurately termed dermal adipose tissue and that, in laboratory mice at least, it represents a separate adipose depot.

File list: ALL.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Oth.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

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Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring.

Directory of Open Access Journals (Sweden)

María Teresa Ramírez-López

Full Text Available Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS. In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a the adult expression of endocannabinoid-related behaviors, b the metabolic profile of adult offspring and c the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed.

Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs

DEFF Research Database (Denmark)

Mentzel, Caroline M. Junker; Cardoso, Tainã Figueiredo; Pipper, Christian Bressen

2018-01-01

The aim of this study was to elucidate the relative impact of three phenotypes often used to characterize obesity on perturbation of molecular pathways involved in obesity. The three obesity-related phenotypes are (1) body mass index (BMI), (2) amount of subcutaneous adipose tissue (SATa), and (3......) amount of retroperitoneal adipose tissue (RPATa). Although it is generally accepted that increasing amount of RPATa is ‘unhealthy’, a direct comparison of the relative impact of the three obesity-related phenotypes on gene expression has, to our knowledge, not been performed previously. We have used...... multiple linear models to analyze altered gene expression of selected obesity-related genes in tissues collected from 19 female pigs phenotypically characterized with respect to the obesity-related phenotypes. Gene expression was assessed by high-throughput qPCR in RNA from liver, skeletal muscle...

From the Cover: Adipose tissue mass can be regulated through the vasculature

Science.gov (United States)

Rupnick, Maria A.; Panigrahy, Dipak; Zhang, Chen-Yu; Dallabrida, Susan M.; Lowell, Bradford B.; Langer, Robert; Judah Folkman, M.

2002-08-01

Tumor growth is angiogenesis dependent. We hypothesized that nonneoplastic tissue growth also depends on neovascularization. We chose adipose tissue as an experimental system because of its remodeling capacity. Mice from different obesity models received anti-angiogenic agents. Treatment resulted in dose-dependent, reversible weight reduction and adipose tissue loss. Marked vascular remodeling was evident in adipose tissue sections, which revealed decreased endothelial proliferation and increased apoptosis in treated mice compared with controls. Continuous treatment maintained mice near normal body weights for age without adverse effects. Metabolic adaptations in food intake, metabolic rate, and energy substrate utilization were associated with anti-angiogenic weight loss. We conclude that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature.

Adipose stem cells for bone tissue repair

OpenAIRE

Ciuffi, Simone; Zonefrati, Roberto; Brandi, Maria Luisa

2017-01-01

Adipose-derived stem/stromal cells (ASCs), together with adipocytes, vascular endothelial cells, and vascular smooth muscle cells, are contained in fat tissue. ASCs, like the human bone marrow stromal/stem cells (BMSCs), can differentiate into several lineages (adipose cells, fibroblast, chondrocytes, osteoblasts, neuronal cells, endothelial cells, myocytes, and cardiomyocytes). They have also been shown to be immunoprivileged, and genetically stable in long-term cultures. Nevertheless, unlik...

Adipose tissue macrophages impair preadipocyte differentiation in humans.

Directory of Open Access Journals (Sweden)

Li Fen Liu

Full Text Available The physiologic mechanisms underlying the relationship between obesity and insulin resistance are not fully understood. Impaired adipocyte differentiation and localized inflammation characterize adipose tissue from obese, insulin-resistant humans. The directionality of this relationship is not known, however. The aim of the current study was to investigate whether adipose tissue inflammation is causally-related to impaired adipocyte differentiation.Abdominal subcutaneous(SAT and visceral(VAT adipose tissue was obtained from 20 human participants undergoing bariatric surgery. Preadipocytes were isolated, and cultured in the presence or absence of CD14+ macrophages obtained from the same adipose tissue sample. Adipocyte differentiation was quantified after 14 days via immunofluorescence, Oil-Red O, and adipogenic gene expression. Cytokine secretion by mature adipocytes cultured with or without CD14+macrophages was quantified.Adipocyte differentiation was significantly lower in VAT than SAT by all measures (p<0.001. With macrophage removal, SAT preadipocyte differentiation increased significantly as measured by immunofluorescence and gene expression, whereas VAT preadipocyte differentiation was unchanged. Adipocyte-secreted proinflammatory cytokines were higher and adiponectin lower in media from VAT vs SAT: macrophage removal reduced inflammatory cytokine and increased adiponectin secretion from both SAT and VAT adipocytes. Differentiation of preadipocytes from SAT but not VAT correlated inversely with systemic insulin resistance.The current results reveal that proinflammatory immune cells in human SAT are causally-related to impaired preadipocyte differentiation, which in turn is associated with systemic insulin resistance. In VAT, preadipocyte differentiation is poor even in the absence of tissue macrophages, pointing to inherent differences in fat storage potential between the two depots.

Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18 F]FDG PET/CT study in mice

International Nuclear Information System (INIS)

Mirbolooki, M. Reza; Upadhyay, Sanjeev Kumar; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

2014-01-01

Objective: Pharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [ 18 F]fluoro-2-deoxyglucose ([ 18 F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice. Methods: A β 3 -adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [ 18 F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images. Results: Activated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [ 18 F]FDG PET images. CL 316243 increased the total [ 18 F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [ 18 F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [ 18 F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU

Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism

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Teresa G. Valencak

2017-08-01

Full Text Available Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions. While the molecular aspects of white and brown adipose biology have become clearer in the recent past, much less is known about sex-specific differences in regulation and deposition of adipose tissue, and the specific role of the so-called pink adipocytes during lactation in females. This review summarises the current understanding of adipose tissue dynamics with a focus on sex-specific differences in adipose tissue energy metabolism and endocrine functions, focussing on mammalian model organisms as well as human-derived data. In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders. Keywords: Body fatness, Adipose tissue, Sex-specific differences, Adipokines, Adipocytes, Obesity, Energy metabolism

Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.

Science.gov (United States)

Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I; Lee, Eunjung; Lawton, Elizabeth; Ong, Helena; Yu, Kristine; Azuma, Yoshihiro; Friedline, Randall H; Lee, Ki Won; Kim, Jason K

2013-05-01

Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

Metabolic characteristics and therapeutic potential of brown and ?beige? adipose tissues

Directory of Open Access Journals (Sweden)

Ekaterina Olegovna Koksharova

2014-10-01

Full Text Available According to the International Diabetes Federation, 10.9 million people have diabetes mellitus (DM in Russia; however, only up to 4 million are registered. In addition, 11.9 million people have impaired glucose tolerance and impaired fasting glucose levels [1]. One of the significant risk factors for type 2 DM (T2DM is obesity, which increases insulin resistance (IR. IR is the major pathogenetic link to T2DM. According to current concepts, there are three types of adipose tissue: white adipose tissue (WAT, brown adipose tissue (BAT and ?beige?, of which the last two types have a thermogenic function. Some research results have revealed the main stages in the development of adipocytes; however, there is no general consensus regarding the development of ?beige? adipocytes. Furthermore, the biology of BAT and ?beige? adipose tissue is currently being intensively investigated, and some key transcription factors, signalling pathways and hormones that promote the development and activation of these tissues have been identified. The most discussed hormones are irisin and fibroblast growth factor 21, which have established positive effects on BAT and ?beige? adipose tissue with regard to carbohydrate, lipid and energy metabolism. The primary imaging techniques used to investigate BAT are PET-CT with 18F-fluorodeoxyglucose and magnetic resonance spectroscopy. With respect to the current obesity epidemic and associated diseases, including T2DM, there is a growing interest in investigating adipogenesis and the possibility of altering this process. BAT and ?beige? adipose tissue may be targets for developing drugs directed against obesity and T2DM.

Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure

NARCIS (Netherlands)

Oedayrajsingh-Varma, M. J.; van Ham, S. M.; Knippenberg, M.; Helder, M. N.; Klein-Nulend, J.; Schouten, T. E.; Ritt, M. J. P. F.; van Milligen, F. J.

2006-01-01

Adipose tissue contains a stromal vascular fraction that can be easily isolated and provides a rich source of adipose tissue-derived mesenchymal stem cells (ASC). These ASC are a potential source of cells for tissue engineering. We studied whether the yield and growth characteristics of ASC were

Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

DEFF Research Database (Denmark)

Ahlqvist, Emma; Osmark, Peter; Kuulasmaa, Tiina

2013-01-01

Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis...... and may play a role in the development of obesity, we explored whether GIP directly would stimulate OPN expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher...... for transmembrane activity. Carriers of the A allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone but also as a trigger of inflammation and insulin resistance in adipose tissue...

Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy.

Science.gov (United States)

Priglinger, Eleni; Schuh, Christina M A P; Steffenhagen, Carolin; Wurzer, Christoph; Maier, Julia; Nuernberger, Sylvia; Holnthoner, Wolfgang; Fuchs, Christiane; Suessner, Susanne; Rünzler, Dominik; Redl, Heinz; Wolbank, Susanne

2017-09-01

Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

File list: InP.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: NoD.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Adp.20.AllAg.Adipose_Tissue,_White hg19 No description Adipocyte Adipose Tissue..., White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Adp.20.AllAg.Adipose_Tissue,_White.bed ...

File list: InP.Adp.20.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Adp.20.AllAg.Adipose_Tissue,_White hg19 Input control Adipocyte Adipose Tissue,... White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Adp.20.AllAg.Adipose_Tissue,_White.bed ...

File list: NoD.Adp.05.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Adp.05.AllAg.Adipose_Tissue,_White hg19 No description Adipocyte Adipose Tissue..., White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Adp.05.AllAg.Adipose_Tissue,_White.bed ...

File list: NoD.Adp.50.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Adp.50.AllAg.Adipose_Tissue,_White hg19 No description Adipocyte Adipose Tissue..., White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Adp.50.AllAg.Adipose_Tissue,_White.bed ...

File list: InP.Adp.10.AllAg.Adipose_Tissue,_White [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Adp.10.AllAg.Adipose_Tissue,_White hg19 Input control Adipocyte Adipose Tissue,... White http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Adp.10.AllAg.Adipose_Tissue,_White.bed ...

Genome-wide effects of acute progressive feed restriction in liver and white adipose tissue

International Nuclear Information System (INIS)

Pohjanvirta, Raimo; Boutros, Paul C.; Moffat, Ivy D.; Linden, Jere; Wendelin, Dominique; Okey, Allan B.

2008-01-01

Acute progressive feed restriction (APFR) represents a specific form of caloric restriction in which feed availability is increasingly curtailed over a period of a few days to a few weeks. It is often used for control animals in toxicological and pharmacological studies on compounds causing body weight loss to equalize weight changes between experimental and control groups and thereby, intuitively, to also set their metabolic states to the same phase. However, scientific justification for this procedure is lacking. In the present study, we analyzed by microarrays the impact on hepatic gene expression in rats of two APFR regimens that caused identical diminution of body weight (19%) but differed slightly in duration (4 vs. 10 days). In addition, white adipose tissue (WAT) was also subjected to the transcriptomic analysis on day-4. The data revealed that the two regimens led to distinct patterns of differentially expressed genes in liver, albeit some major pathways of energy metabolism were similarly affected (particularly fatty acid and amino acid catabolism). The reason for the divergence appeared to be entrainment by the longer APFR protocol of peripheral oscillator genes, which resulted in derailment of circadian rhythms and consequent interaction of altered diurnal fluctuations with metabolic adjustments in gene expression activities. WAT proved to be highly unresponsive to the 4-day APFR as only 17 mRNA levels were influenced by the treatment. This study demonstrates that body weight is a poor proxy of metabolic state and that the customary protocols of feed restriction can lead to rhythm entrainment

The relationship between bone mineral density and adipose tissue of postmenopausal women

Energy Technology Data Exchange (ETDEWEB)

Kim, Sun Hwa [Dept. of Radiology, HwaMyeong Iisin christian Hospital, Busan (Korea, Republic of); Kim, Jung Hoon [Dept. of Radiological Science, Catholic University of Pusan, Busan (Korea, Republic of); Im, In Chul [Dept. of Radiological Science, Dong Eui University, Busan (Korea, Republic of)

2017-06-15

Postmenopausal women are at increased risk for osteoporosis and obesity due to changes in hormones. The relationship between osteoporosis and body weight is known, and its relation with body fat mass is discussed. The purpose of this study was to evaluate the bone mineral density(BMD) changes of epicardial adipose tissue(EAT) and abdominal subcutaneous fat. The subjects of this study were 160 postmenopausal women who underwent BMD and echocardiography. The thickness of the epicardial adipose tissue was measured in three sections and the BMD were meassured according to the diagnostic criteria. The results of this study that age increase the risk of osteoporosis increases, and as the weight and BMI decrease, the risk of osteoporosis increases(p<0.05). The relationship between changes in bone mineral density and adipose tissue in postmenopausal women, increased epicardial adipose tissue was negatively correlated with the bone mineral density(p<0.05). conversely, increased abdominal subcutaneous fat thickness was positively correlated with bone mineral density(p<0.05). In other words, the effect of bone mineral density on the location of adipose tissue was different. If Echocardiography is used to periodically examine changes in the thickness of the epicardial adipose tissue, it may be prevented before proceeding to osteoporosis.

Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge

DEFF Research Database (Denmark)

Emmett, Matthew J.; Lim, Hee-Woong; Jager, Jennifer

2017-01-01

Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease1. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold...

Neurotensin Is a Lipid-Induced Gastrointestinal Peptide Associated with Visceral Adipose Tissue Inflammation in Obesity.

Science.gov (United States)

Barchetta, Ilaria; Cimini, Flavia Agata; Capoccia, Danila; Bertoccini, Laura; Ceccarelli, Valentina; Chiappetta, Caterina; Leonetti, Frida; Di Cristofano, Claudio; Silecchia, Gianfranco; Orho-Melander, Marju; Melander, Olle; Cavallo, Maria Gisella

2018-04-23

Neurotensin (NT) is a 13-amino acid peptide localized in the neuroendocrine cells of the small intestine, which promotes fat absorption and fatty acids translocation in response to lipid ingestion. NT-knock-out mice fed with a high-fat diet are protected from obesity, fatty liver, and the development of insulin-resistance. In humans, higher plasma levels of pro-NT, which is the stable circulating precursor of NT, predict obesity, type 2 diabetes (T2D), and cardiovascular disease. In obesity, the presence of visceral adipose tissue (VAT) inflammation leads to unfavorable metabolic outcomes and is associated with the development of T2D and non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the relationship between plasma pro-NT levels and the presence of VAT inflammation in biopsies from 40 morbidly obese subjects undergoing bariatric surgery. We demonstrated that higher proNT levels are significantly associated with greater macrophages infiltration, HIF-1α, WISP-1, and UNC5B expression in VAT (all p < 0.01) due to the diagnosis of T2D and NAFLD. The overall results show that, in obesity, pro-NT is a biomarker of VAT inflammation and insulin-resistance. Additionally, NT may be involved in the development of dysmetabolic conditions likely mediated by increased gut fat absorption and the presence of a proinflammatory milieu in the adipose tissue.

Visceral Adiposity Index: An Indicator of Adipose Tissue Dysfunction

Directory of Open Access Journals (Sweden)

Marco Calogero Amato

2014-01-01

Full Text Available The Visceral Adiposity Index (VAI has recently proven to be an indicator of adipose distribution and function that indirectly expresses cardiometabolic risk. In addition, VAI has been proposed as a useful tool for early detection of a condition of cardiometabolic risk before it develops into an overt metabolic syndrome. The application of the VAI in particular populations of patients (women with polycystic ovary syndrome, patients with acromegaly, patients with NAFLD/NASH, patients with HCV hepatitis, patients with type 2 diabetes, and general population has produced interesting results, which have led to the hypothesis that the VAI could be considered a marker of adipose tissue dysfunction. Unfortunately, in some cases, on the same patient population, there is conflicting evidence. We think that this could be mainly due to a lack of knowledge of the application limits of the index, on the part of various authors, and to having applied the VAI in non-Caucasian populations. Future prospective studies could certainly better define the possible usefulness of the VAI as a predictor of cardiometabolic risk.

Early overfeed-induced obesity leads to brown adipose tissue hypoactivity in rats.

Science.gov (United States)

de Almeida, Douglas L; Fabrício, Gabriel S; Trombini, Amanda B; Pavanello, Audrei; Tófolo, Laize P; da Silva Ribeiro, Tatiane A; de Freitas Mathias, Paulo C; Palma-Rigo, Kesia

2013-01-01

Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups) and small (3 pups) litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C) and dark (NL 38°C vs. SL 37.6°C) periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (p<0.01), and no difference was observed in the sympathetic nerve activity. In adulthood, the small litter rats were 11,7% heavier than the controls and presented higher glycemia 13,1%, insulinemia 70% and corticosteronemia 92,6%. Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults. © 2013 S. Karger AG, Basel.

Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

DEFF Research Database (Denmark)

Arngrim, Nanna Bjørkbom; Simonsen, L; Holst, J J

2013-01-01

The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after ...... online publication, 3 July 2012; doi:10.1038/ijo.2012.98....

Relationship between reflection spectra of breast adipose tissue with histologic grade

Science.gov (United States)

Muñoz Morales, Aarón; Vázquez Y Montiel, Sergio; Reigosa, Aldo

2011-08-01

Optical spectroscopy allows the characterization, recognition and differentiation of subcutaneous tissues healthy and no-healthy, to facilitate the diagnosis or early detection for breast cancer are studied white adipose tissue by the subcutaneous region with the help of the diffuse reflection spectroscopy in the visible areas (400 to 700 nm) of electromagnetic spectrum for them using a spectrometer portable of integrating sphere, Hunter lab Model Mini-Scan. The problem to be solved for cancer detection by optical techniques is to find the solution to the inverse problem of scattering of radiation in tissue where it is necessary to solve the equation of energy transfer. us through the trigonometric interpolation and by the data adjustment by least squares using Fourier series expansion to parameterize the spectral response curves of each sample of breast adipose tissue then correlated with histological grades established by the optical biopsy for each one of the samples, allowing use this technique to the study of anomalies in White Adipose Tissue Breast, changes are evident in the spectral response for Breast Adipose Tissue carcinogens with respect to healthy tissues and for the different histological grades.

Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans

DEFF Research Database (Denmark)

Mulla, N A; Simonsen, L; Bülow, J

2000-01-01

, a subcutaneous abdominal vein and a femoral vein. Adipose tissue metabolism and skeletal muscle (leg) metabolism were measured using Fick's principle. The results show that the lipolytic rate in adipose tissue during exercise was the same in each experiment. Post-exercise, there was a very fast decrease......One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid...... metabolism during a 3 h post-exercise period. Six subjects were studied twice. In one experiment, they exercised for 90 min at 40% of maximal O2 consumption (VO2,max) and in the other experiment they exercised at 60% VO2,max for 60 min. For both experiments, catheters were inserted in an artery...

Determination of the tissue-to-blood partition coefficient for 131iodo-antipyrine in human subcutaneous adipose tissue

DEFF Research Database (Denmark)

Jelnes, R; Astrup, A

1985-01-01

131Iodo-antipyrine (131I-AP) is commonly used for blood flow measurements in adipose tissue. These estimations have been based on the assumption of the tissue-to-blood partition coefficient being 1 ml g-1. No exact determination of the tissue-to-blood partition coefficient for 131I-AP in adipose...... tissue has been carried out. In the present study a partition coefficient of 1.12 +/- 0.06 (mean +/- S.D.) for 131I-AP in adipose tissue has been determined based on the partition coefficient for 131I-AP between lipid-saline (1.24 ml g-1), red blood cells-plasma (0.64 ml g-1), protein-saline (0.19 ml g-1...

Effect of luminescence transport through adipose tissue on measurement of tissue temperature by using ZnCdS nanothermometers

Science.gov (United States)

Volkova, Elena K.; Yanina, Irina Yu.; Sagaydachnaya, Elena; Konyukhova, Julia G.; Kochubey, Vyacheslav I.; Tuchin, Valery V.

2018-02-01

The spectra of luminescence of ZnCdS nanoparticles (ZnCdS NPs) were measured and analyzed in a wide temperature range: from room to human body and further to a hyperthermic temperature resulting in tissue morphology change. The results show that the signal of luminescence of ZnCdS NPs placed within the tissue is reasonably good sensitive to temperature change and accompanied by phase transitions of lipid structures of adipose tissue. It is shown that the presence of a phase transition in adipose tissue upon its heating (polymorphic transformations of lipids) leads to a nonmonotonic temperature dependence of the intensity of luminescence for the nanoparticles introduced into adipose tissue. This is due to a change in the light scattering by the tissue. The light scattering of adipose tissue greatly distorts the results of temperature measurements. The application of these nanoparticles is possible for temperature measurements in very thin or weakly scattering samples.

A role for TLR10 in obesity and adipose tissue morphology

NARCIS (Netherlands)

Boutens, Lily; Mirea, Andreea Manuela; Munckhof, van den Inge; Doppenberg-Oosting, Marije; Jaeger, Martin; Hijmans, Anneke; Netea, Mihai G.; Joosten, Leo A.B.; Stienstra, Rinke

2018-01-01

Toll like receptors (TLRs) are expressed in adipose tissue and promote adipose tissue inflammation during obesity. Recently, anti-inflammatory properties have been attributed to TLR10 in myeloid cells, the only member of the TLR family with inhibitory activity. In order to assess whether

Biology and function of adipose tissue macrophages, dendritic cells and B cells.

Science.gov (United States)

Ivanov, Stoyan; Merlin, Johanna; Lee, Man Kit Sam; Murphy, Andrew J; Guinamard, Rodolphe R

2018-04-01

The increasing incidence of obesity and its socio-economical impact is a global health issue due to its associated co-morbidities, namely diabetes and cardiovascular disease [1-5]. Obesity is characterized by an increase in adipose tissue, which promotes the recruitment of immune cells resulting in low-grade inflammation and dysfunctional metabolism. Macrophages are the most abundant immune cells in the adipose tissue of mice and humans. The adipose tissue also contains other myeloid cells (dendritic cells (DC) and neutrophils) and to a lesser extent lymphocyte populations, including T cells, B cells, Natural Killer (NK) and Natural Killer T (NKT) cells. While the majority of studies have linked adipose tissue macrophages (ATM) to the development of low-grade inflammation and co-morbidities associated with obesity, emerging evidence suggests for a role of other immune cells within the adipose tissue that may act in part by supporting macrophage homeostasis. In this review, we summarize the current knowledge of the functions ATMs, DCs and B cells possess during steady-state and obesity. Copyright © 2018 Elsevier B.V. All rights reserved.

Diurnal gene expression of lipolytic natriuretic peptide receptors in white adipose tissue

DEFF Research Database (Denmark)

Smith, Julie; Fahrenkrug, Jan; Jørgensen, Henrik L

2015-01-01

Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart, but the tem......Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart......, but the temporal expression profile of their cognate receptors has not been examined in white adipose tissue. We therefore collected peri-renal white adipose tissue and serum from WT mice. Tissue mRNA contents of NPRs - NPR-A and NPR-C, the clock genes Per1 and Bmal1, and transcripts involved in lipid metabolism...... in serum peaked in the active dark period (P=0.003). In conclusion, NPR-A and NPR-C gene expression is associated with the expression of clock genes in white adipose tissue. The reciprocal expression may thus contribute to regulate lipolysis and energy homeostasis in a diurnal manner....

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

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Avril, Pierre; Duteille, Franck; Ridel, Perrine; Heymann, Marie-Françoise; De Pinieux, Gonzague; Rédini, Françoise; Blanchard, Frédéric; Heymann, Dominique; Trichet, Valérie; Perrot, Pierre

2016-03-01

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed. Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed. Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres. This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

Adipose tissue Fatty Acid patterns and changes in antrhropometry

DEFF Research Database (Denmark)

Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre

2011-01-01

Introduction Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns...... in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate...... the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WCBMI), adjusting for confounders. Results 7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men...

Feast and famine: Adipose tissue adaptations for healthy aging.

Science.gov (United States)

Lettieri Barbato, Daniele; Aquilano, Katia

2016-07-01

Proper adipose tissue function controls energy balance with favourable effects on metabolic health and longevity. The molecular and metabolic asset of adipose tissue quickly and dynamically readapts in response to nutrient fluctuations. Once delivered into cells, nutrients are managed by mitochondria that represent a key bioenergetics node. A persistent nutrient overload generates mitochondrial exhaustion and uncontrolled reactive oxygen species ((mt)ROS) production. In adipocytes, metabolic/molecular reorganization is triggered culminating in the acquirement of a hypertrophic and hypersecretory phenotype that accelerates aging. Conversely, dietary regimens such as caloric restriction or time-controlled fasting endorse mitochondrial functionality and (mt)ROS-mediated signalling, thus promoting geroprotection. In this perspective view, we argued some important molecular and metabolic aspects related to adipocyte response to nutrient stress. Finally we delineated hypothetical routes by which molecularly and metabolically readapted adipose tissue promotes healthy aging. Copyright © 2016 Elsevier B.V. All rights reserved.

Adipose tissue and adrenal glands: novel pathophysiological mechanisms and clinical applications.

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Kargi, Atil Y; Iacobellis, Gianluca

2014-01-01

Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or "adipokines" have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of "cross talk" between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals.

Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications

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Atil Y. Kargi

2014-01-01

Full Text Available Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or “adipokines” have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of “cross talk” between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals.

Disconnect Between Adipose Tissue Inflammation and Cardiometabolic Dysfunction in Ossabaw Pigs

Science.gov (United States)

Vieira-Potter, Victoria J.; Lee, Sewon; Bayless, David S.; Scroggins, Rebecca J.; Welly, Rebecca J.; Fleming, Nicholas J.; Smith, Thomas N.; Meers, Grace M.; Hill, Michael A.; Rector, R. Scott; Padilla, Jaume

2015-01-01

Objective The Ossabaw pig is emerging as an attractive model of human cardiometabolic disease due to its size and susceptibility to atherosclerosis, among other characteristics. Here we investigated the relationship between adipose tissue inflammation and metabolic dysfunction in this model. Methods Young female Ossabaw pigs were fed a western-style high-fat diet (HFD) (n=4) or control low-fat diet (LFD) (n=4) for a period of 9 months and compared for cardiometabolic outcomes and adipose tissue inflammation. Results The HFD-fed “OBESE” pigs were 2.5 times heavier (p<0.001) than LFD-fed “LEAN” pigs and developed severe obesity. HFD-feeding caused pronounced dyslipidemia, hypertension, insulin resistance (systemic and adipose) as well as induction of inflammatory genes, impairments in vasomotor reactivity to insulin and atherosclerosis in the coronary arteries. Remarkably, visceral, subcutaneous and perivascular adipose tissue inflammation (via FACS analysis and RT-PCR) was not increased in OBESE pigs, nor were circulating inflammatory cytokines. Conclusions These findings reveal a disconnect between adipose tissue inflammation and cardiometabolic dysfunction induced by western diet feeding in the Ossabaw pig model. PMID:26524201

Tissue/blood partition coefficients for xenon in various adipose tissue depots in man

DEFF Research Database (Denmark)

Bülow, J; Jelnes, Rolf; Astrup, A

1987-01-01

Tissue/blood partition coefficients (lambda) for xenon were calculated for subcutaneous adipose tissue from the abdominal wall and the thigh, and for the perirenal adipose tissue after chemical analysis of the tissues for lipid, water and protein content. The lambda in the perirenal tissue...... was found to correlate linearly to the relative body weight (RBW) in per cent with the regression equation lambda = 0.045 . RBW + 0.99. The subcutaneous lambda on the abdomen correlated linearly to the local skinfold thickness (SFT) with the equation lambda = 0.22 SFT + 2.99. Similarly lambda on the thigh...... correlated to SFT with the equation lambda = 0.20 . SFT + 4.63. It is concluded that the previously accepted lambda value of 10 is generally too high in perirenal as well as in subcutaneous tissue. Thus, by application of the present regression equations, it is possible to obtain more exact estimates...

Central melanin-concentrating hormone influences liver and adipose metabolism via specific hypothalamic nuclei and efferent autonomic/JNK1 pathways.

OpenAIRE

Imbernon, Monica; Beiroa, Daniel; Vázquez, María J.; Morgan, Donald A.; Veyrat–Durebex, Christelle; Porteiro, Begoña; Díaz–Arteaga, Adenis; Senra, Ana; Busquets, Silvia; Velásquez, Douglas A.; Al–Massadi, Omar; Varela, Luis; Gándara, Marina; López–Soriano, Francisco–Javier; Gallego, Rosalía

2013-01-01

BACKGROUND AIMS Specific neuronal circuits modulate autonomic outflow to liver and white adipose tissue. Melanin concentrating hormone (MCH) deficient mice are hypophagic lean and do not develop hepatosteatosis when fed a high fat diet. Herein we sought to investigate the role of MCH an orexigenic neuropeptide specifically expressed in the lateral hypothalamic area on hepatic and adipocyte metabolism. METHODS Chronic central administration of MCH and adenoviral vectors increasing MCH sign...

Pituitary adenoma with adipose tissue: A new metaplastic variant.

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Caporalini, Chiara; Buccoliero, Anna Maria; Pansini, Luigi; Moscardi, Selene; Novelli, Luca; Baroni, Gianna; Bordi, Lorenzo; Ammannati, Franco; Taddei, Gian Luigi

2017-08-01

Pituitary adenomas are benign tumors representing approximately 15-20% of intracranial neoplasms. There have been few reports of metaplastic osseous transformation and about 60 cases of neuronal metaplasia in pituitary adenoma but adipose metaplasia has not been previously described in the English literature. Here we report a case of pituitary adenoma with metaplastic adipose tissue in a 58-year-old male patient. Histologically this case fulfilled the criteria of a non-functioning pituitary adenoma, and moreover a central area of adipose tissue, made by mature adipocytes, and many tumor cells, containing fat droplet were evident. Lipomatous transformation of tumor cells in the CNS has been previously observed but, to the best of our knowledge, our case is the first pituitary adenoma with such change. The histogenesis of the adipose element in pituitary adenoma is not well understood, and could be a result of a metaplastic change or divergent differentiation from a common progenitor cell. © 2017 Japanese Society of Neuropathology.

[Cancer cachexia and white adipose tissue browning].

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Zhang, S T; Yang, H M

2016-08-01

Cancer cachexia occurs in a majority of advanced cancer patients. These patients with impaired physical function are unable to tolerance cancer treatment well and have a significantly reduced survival rate. Currently, there is no effective clinical treatment available for cancer cachexia, therefore, it is necessary to clarify the molecular mechanisms of cancer cachexia, moreover, new therapeutic targets for cancer cachexia treatment are urgently needed. Very recent studies suggest that, during cancer cachexia, white adipose tissue undergo a 'browning' process, resulting in increased lipid mobilization and energy expenditure, which may be necessary for the occurrence of cancer cachexia. In this article, we summarize the definition and characteristics of cancer cachexia and adipose tissue 'browning', then, we discuss the new study directions presented in latest research.

Effect of training on epinephrine-stimulated lipolysis determined by microdialysis in human adipose tissue

DEFF Research Database (Denmark)

Stallknecht, B; Simonsen, L; Bülow, J

1995-01-01

glycerol concentrations (Tr: 129 +/- 36 microM; Sed: 119 +/- 56) did not differ between groups. It is concluded that in intact subcutaneous adipose tissue epinephrine-stimulated blood flow is enhanced, whereas lipolytic sensitivity to epinephrine is the same in trained compared with untrained subjects.......Trained humans (Tr) have a higher fat oxidation during submaximal physical work than sedentary humans (Sed). To investigate whether this reflects a higher adipose tissue lipolytic sensitivity to catecholamines, we infused epinephrine (0.3 nmol.kg-1.min-1) for 65 min in six athletes and six...... sedentary young men. Glycerol was measured in arterial blood, and intercellular glycerol concentrations in abdominal subcutaneous adipose tissue were measured by microdialysis. Adipose tissue blood flow was measured by 133Xe-washout technique. From these measurements adipose tissue lipolysis was calculated...

Objectively Quantified Physical Activity and Sedentary Behavior in Predicting Visceral Adiposity and Liver Fat

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Shelley E. Keating

2016-01-01

Full Text Available Objective. Epidemiologic studies suggest an inverse relationship between nonalcoholic fatty liver disease (NAFLD, visceral adipose tissue (VAT, and self-reported physical activity levels. However, subjective measurements can be inaccurate and prone to reporter bias. We investigated whether objectively quantified physical activity levels predicted liver fat and VAT in overweight/obese adults. Methods. Habitual physical activity was measured by triaxial accelerometry for four days (n=82. Time spent in sedentary behavior (MET < 1.6 and light (MET 1.6 < 3, moderate (MET 3 < 6, and vigorous (MET 6 < 9 physical activity was quantified. Magnetic resonance imaging and spectroscopy were used to quantify visceral and liver fat. Bivariate correlations and hierarchical multiple regression analyses were performed. Results. There were no associations between physical activity or sedentary behavior and liver lipid. Sedentary behavior and moderate and vigorous physical activity accounted for just 3% of variance for VAT (p=0.14 and 0.003% for liver fat (p=0.96. Higher levels of VAT were associated with time spent in moderate activity (r=0.294, p=0.007, but there was no association with sedentary behavior. Known risk factors for obesity-related NAFLD accounted for 62% and 40% of variance in VAT and liver fat, respectively (p<0.01. Conclusion. Objectively measured levels of habitual physical activity and sedentary behavior did not influence VAT or liver fat.

Global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (PCOS).

Science.gov (United States)

Borruel, Susana; Fernández-Durán, Elena; Alpañés, Macarena; Martí, David; Alvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2013-03-01

Sexual dimorphism suggests a role for androgens in body fat distribution. Women with polycystic ovary syndrome (PCOS), a mainly androgen excess disorder, often present with abdominal obesity and visceral adiposity. We hypothesized that women with PCOS have a masculinized body fat distribution favoring the deposition of fat in visceral and organ-specific adipose tissue depots. This was a case-control study. The study was conducted at an academic hospital. Women with PCOS (n = 55), women without androgen excess (n = 25), and men (n = 26) presenting with similar body mass index participated in the study. There were no interventions. Ultrasound measurements of adipose tissue depots including sc (minimum and maximum), preperitoneal, ip, mesenteric, epicardial, and perirenal fat thickness were obtained and total body fat mass was estimated using a body fat monitor. Men and patients with PCOS had increased amounts of total body fat compared with control women. Men had increased thickness of intraabdominal adipose tissue depots compared with the control women, with the women with PCOS showing intermediate values that were also higher than those of control women in the case of ip and mesenteric fat thickness and was close to reaching statistical significance in the case of epicardial fat thickness. Women with PCOS also showed increased minimum sc fat thickness compared with the control women. Obesity increased the thickness of all of the adipose tissue depots in the 3 groups of subjects. Women with PCOS have higher global adiposity and increased amounts of visceral adipose tissue compared with control women, especially in the ip and mesenteric depots.

Regular aerobic exercise correlates with reduced anxiety and incresed levels of irisin in brain and white adipose tissue.

Science.gov (United States)

Uysal, Nazan; Yuksel, Oguz; Kizildag, Servet; Yuce, Zeynep; Gumus, Hikmet; Karakilic, Aslı; Guvendi, Guven; Koc, Basar; Kandis, Sevim; Ates, Mehmet

2018-05-29

We have recently shown that regular voluntary aerobic exercised rats have low levels of anxiety. Irisin is an exercise-induced myokine that is produced by many tissues; and the role it plays in anxiolytic behavior is unknown. In this study we aimed to investigate the correlation between anxiety like behavior and irisin levels following regular voluntary aerobic exercise in male mice. We've have shown that anxiety levels decreased in exercised mice, while irisin levels increased in the brain, brown adipose tissue, white adipose tissue, kidney, and pancreas tissues. No significant difference of irisin levels in the liver, muscle and serum were detected in the exercise group, when compared to controls. In addition, there was a strong positive correlation between brain irisin levels and activity in middle area of open field test and in the open arms of elevated plus maze test; both which are indicators of low anxiety levels. Our results suggest that decrease in anxiolytic behavior due to regular voluntary exercise may be associated with locally produced brain irisin. White adipose tissue irisin levels also correlated very strongly with low anxiety. However, no serum irisin increase was detected, ruling out the possibility of increased peripheral irisin levels affecting the brain via the bloodstream. Further research is necessary to explain the mechanisms of which peripheral and central irisin effects anxiety and the brain region affected. Copyright © 2018 Elsevier B.V. All rights reserved.

Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues.

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Liaw, Lucy; Prudovsky, Igor; Koza, Robert A; Anunciado-Koza, Rea V; Siviski, Matthew E; Lindner, Volkhard; Friesel, Robert E; Rosen, Clifford J; Baker, Paul R S; Simons, Brigitte; Vary, Calvin P H

2016-09-01

Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MS(ALL) . Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MS(ALL) data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. J. Cell. Biochem. 117: 2182-2193, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Substance for thermoluminescent dosimetry of photon radiation in adipose tissue

International Nuclear Information System (INIS)

Kalmykov, L.Z.; Kandel', T.G.

1983-01-01

Substance composition for thermoluminescent photon dosimetry in adipose tissue is proposed which makes it possible to simplify dosimetric measurements and to improve their accuracy. The substance consists of powder-like thermoluminophor Li 2 B 4 O 7 (0.03%Mn) 48-52 mass % and bistriethylammonium dodecahydrododecaborane - 48-52 mass %. The above substance is equivalent in respect to dosimetry to adipose tissue within the 10 keV - 10 MeV energy range

White adipose tissue coloring by intermittent fasting.

Science.gov (United States)

Kivelä, Riikka; Alitalo, Kari

2017-11-01

Intermittent fasting (IF) has been shown to promote metabolic health in several organisms. Two recent papers show that IF induces white adipose tissue beiging and increases thermogenesis, which improves metabolic health in mice.

Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

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Carolina De Fusco

2017-01-01

Full Text Available Osteopontin (OPN is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

Osteopontin: Relation between Adipose Tissue and Bone Homeostasis.

Science.gov (United States)

De Fusco, Carolina; Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Moscatelli, Fiorenzo; Valenzano, Anna; Esposito, Teresa; Sergio, Chieffi; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

2017-01-01

Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

Fasting-induced G0/G1 switch gene 2 and FGF21 expression in the liver are under regulation of adipose tissue derived fatty acids

Science.gov (United States)

Jaeger, Doris; Schoiswohl, Gabriele; Hofer, Peter; Schreiber, Renate; Schweiger, Martina; Eichmann, Thomas O.; Pollak, Nina M.; Poecher, Nadja; Grabner, Gernot F.; Zierler, Kathrin A.; Eder, Sandra; Kolb, Dagmar; Radner, Franz P.W.; Preiss-Landl, Karina; Lass, Achim; Zechner, Rudolf; Kershaw, Erin E.; Haemmerle, Guenter

2015-01-01

Background & Aims Adipose tissue (AT)-derived fatty acids (FAs) are utilized for hepatic triacylglycerol (TG) generation upon fasting. However, their potential impact as signaling molecules is not established. Herein we examined the role of exogenous AT-derived FAs in the regulation of hepatic gene expression by investigating mice with a defect in AT-derived FA supply to the liver. Methods Plasma FA levels, tissue TG hydrolytic activities and lipid content were determined in mice lacking the lipase co-activator comparative gene identification-58 (CGI-58) selectively in AT (CGI-58-ATko) applying standard protocols. Hepatic expression of lipases, FA oxidative genes, transcription factors, ER stress markers, hormones and cytokines were determined by qRT-PCR, Western blotting and ELISA. Results Impaired AT-derived FA supply upon fasting of CGI-58-ATko mice causes a marked defect in liver PPARα-signaling and nuclear CREBH translocation. This severely reduced the expression of respective target genes such as the ATGL inhibitor G0/G1 switch gene-2 (G0S2) and the endocrine metabolic regulator FGF21. These changes could be reversed by lipid administration and raising plasma FA levels. Impaired AT-lipolysis failed to induce hepatic G0S2 expression in fasted CGI-58-ATko mice leading to enhanced ATGL-mediated TG-breakdown strongly reducing hepatic TG deposition. On high fat diet, impaired AT-lipolysis counteracts hepatic TG accumulation and liver stress linked to improved systemic insulin sensitivity. Conclusions AT-derived FAs are a critical regulator of hepatic fasting gene expression required for the induction of G0S2-expression in the liver to control hepatic TG-breakdown. Interfering with AT-lipolysis or hepatic G0S2 expression represents an effective strategy for the treatment of hepatic steatosis. PMID:25733154

Liver fat, visceral adiposity, and sleep disturbances contribute to the development of insulin resistance and glucose intolerance in nondiabetic dialysis patients.

Science.gov (United States)

Sakkas, Giorgos K; Karatzaferi, Christina; Zintzaras, Elias; Giannaki, Christoforos D; Liakopoulos, Vassilios; Lavdas, Eleftherios; Damani, Eleni; Liakos, Nikos; Fezoulidis, Ioannis; Koutedakis, Yiannis; Stefanidis, Ioannis

2008-12-01

Hemodialysis patients exhibit insulin resistance (IR) in target organs such as liver, muscles, and adipose tissue. The aim of this study was to identify contributors to IR and to develop a model for predicting glucose intolerance in nondiabetic hemodialysis patients. After a 2-h, 75-g oral glucose tolerance test (OGTT), 34 hemodialysis patients were divided into groups with normal (NGT) and impaired glucose tolerance (IGT). Indices of insulin sensitivity were derived from OGTT data. Measurements included liver and muscle fat infiltration and central adiposity by computed tomography scans, body composition by dual energy X-ray absorptiometer, sleep quality by full polysomnography, and functional capacity and quality of life (QoL) by a battery of exercise tests and questionnaires. Cut-off points, as well as sensitivity and specificity calculations were based on IR (insulin sensitivity index by Matsuda) using a receiver operator characteristics (ROC) curve analysis. Fifteen patients were assigned to the IGT, and 19 subjects to the NGT group. Intrahepatic fat content and visceral adiposity were significantly higher in the IGT group. IR indices strongly correlated with sleep disturbances, visceral adiposity, functional capacity, and QoL. Visceral adiposity, O2 desaturation during sleep, intrahepatic fat content, and QoL score fitted into the model for predicting glucose intolerance. A ROC curve analysis identified an intrahepatic fat content of > 3.97% (sensitivity, 100; specificity, 35.7) as the best cutoff point for predicting IR. Visceral and intrahepatic fat content, as well as QoL and sleep seemed to be involved at some point in the development of glucose intolerance in hemodialysis patients. Means of reducing fat depots in the liver and splachnic area might prove promising in combating IR and cardiovascular risk in hemodialysis patients.

Identification of differentially expressed genes induced by energy restriction using annealing control primer system from the liver and adipose tissues of broilers.

Science.gov (United States)

Wang, J W; Chen, W; Kang, X T; Huang, Y Q; Tian, Y D; Wang, Y B

2012-04-01

Female Arbor Acre broilers were divided into 2 groups at 18 d of age. One group of chickens had free access to feed (AL), and the other group of chickens had 30% energy restriction (ER). Adipose and hepatic RNA samples were collected at 48 d of age. We employed an accurate reverse-transcription (RT) PCR method that involves annealing control primers to identify the differentially expressed genes (DEG) between ER and AL groups. Using 20 annealing control primers, 43 differentially expressed bands (40 downregulated and 3 upregulated in the ER group) were detected from the hepatic tissue, whereas no differentially expressed bands were detected from the adipose tissue. It seems that energy restriction could induce more DEG in hepatic tissue than that in adipose tissue and could result in more gene-expression downregulation in hepatic tissue. Eight DEG (6 known and 2 unknown genes) were gained from hepatic tissue and confirmed by RT-PCR, which were all supported by released expressed sequence tag sequences. Their expressions were all downregulated by energy restriction in hepatic tissues. Six known genes are RPL7, RPLP1, FBXL12, ND1, ANTXR2, and SLC22A18, respectively, which seem to play essential roles in the protein translation, energy metabolism, and tumor inhibition. The alterations of gene expression in 3 selected genes, including ND1 (P < 0.01), FBXL12 (P < 0.01), and RPLP1 (P < 0.05), were supported by real-time quantitative RT-PCR reaction. Our data provide new insights on the metabolic state of broilers changed by energy restriction.

Development of Synthetic and Natural Materials for Tissue Engineering Applications Using Adipose Stem Cells

Directory of Open Access Journals (Sweden)

Yunfan He

2016-01-01

Full Text Available Adipose stem cells have prominent implications in tissue regeneration due to their abundance and relative ease of harvest from adipose tissue and their abilities to differentiate into mature cells of various tissue lineages and secrete various growth cytokines. Development of tissue engineering techniques in combination with various carrier scaffolds and adipose stem cells offers great potential in overcoming the existing limitations constraining classical approaches used in plastic and reconstructive surgery. However, as most tissue engineering techniques are new and highly experimental, there are still many practical challenges that must be overcome before laboratory research can lead to large-scale clinical applications. Tissue engineering is currently a growing field of medical research; in this review, we will discuss the progress in research on biomaterials and scaffolds for tissue engineering applications using adipose stem cells.

Is adipose tissue a place for Mycobacterium tuberculosis persistence?

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Olivier Neyrolles

Full Text Available BACKGROUND: Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB, has the ability to persist in its human host for exceptionally long periods of time. However, little is known about the location of the bacilli in latently infected individuals. Long-term mycobacterial persistence in the lungs has been reported, but this may not sufficiently account for strictly extra-pulmonary TB, which represents 10-15% of the reactivation cases. METHODOLOGY/PRINCIPAL FINDINGS: We applied in situ and conventional PCR to sections of adipose tissue samples of various anatomical origins from 19 individuals from Mexico and 20 from France who had died from causes other than TB. M. tuberculosis DNA could be detected by either or both techniques in fat tissue surrounding the kidneys, the stomach, the lymph nodes, the heart and the skin in 9/57 Mexican samples (6/19 individuals, and in 8/26 French samples (6/20 individuals. In addition, mycobacteria could be immuno-detected in perinodal adipose tissue of 1 out of 3 biopsy samples from individuals with active TB. In vitro, using a combination of adipose cell models, including the widely used murine adipose cell line 3T3-L1, as well as primary human adipocytes, we show that after binding to scavenger receptors, M. tuberculosis can enter within adipocytes, where it accumulates intracytoplasmic lipid inclusions and survives in a non-replicating state that is insensitive to the major anti-mycobacterial drug isoniazid. CONCLUSIONS/SIGNIFICANCE: Given the abundance and the wide distribution of the adipose tissue throughout the body, our results suggest that this tissue, among others, might constitute a vast reservoir where the tubercle bacillus could persist for long periods of time, and avoid both killing by antimicrobials and recognition by the host immune system. In addition, M. tuberculosis-infected adipocytes might provide a new model to investigate dormancy and to evaluate new drugs for the treatment of

Adiposity, lipogenesis, and fatty acid composition of subcutaneous and intramuscular adipose tissues of Brahman and Angus crossbred cattle.

Science.gov (United States)

Campbell, E M G; Sanders, J O; Lunt, D K; Gill, C A; Taylor, J F; Davis, S K; Riley, D G; Smith, S B

2016-04-01

The objective of this study was to demonstrate differences in aspects of adipose tissue cellularity, lipid metabolism, and fatty and cholesterol composition in Angus and Brahman crossbred cattle. We hypothesized that in vitro measures of lipogenesis would be greater in three-fourths Angus progeny than in three-fourths Brahman progeny, especially in intramuscular (i.m.) adipose tissue. Progeny ( = 227) were fed a standard, corn-based diet for approximately 150 d before slaughter. Breed was considered to be the effect of interest and was forced into the model. There were 9 breed groups including all 4 kinds of three-fourths Angus calves: Angus bulls Angus-sired F cows ( = 32), Angus bulls Brahman-sired F cows ( = 20), Brahman-sired F bulls Angus cows ( = 24), and Angus-sired F bulls Angus cows ( = 20). There were all 4 kinds of three-fourths Brahman calves: Brahman bulls Brahman-sired F cows ( = 21), Brahman bulls Angus-sired F cows ( = 43), Brahman-sired F bulls Brahman cows ( = 26), and Angus-sired F bulls Brahman cows ( = 13). Additionally, F calves (one-half Brahman and one-half Angus) were produced only from Brahman-sired F bulls Angus-sired F cows ( = 28). Contrasts were calculated when breed was an important fixed effect, using the random effect family(breed) as the error term. Most contrasts were nonsignificant ( > 0.10). Those that were significant ( Angus > F, three-fourths Brahman > F, and three-fourths crossbred progeny combined > F), s.c. adipocyte volume (three-fourths Angus > F and three-fourths bloods combined > F), lipogenesis from acetate in s.c. adipose tissue (three-fourths Brahman calves from Brahman dams > three-fourths Brahman calves from F dams), and percentage 18:3-3 in s.c. adipose tissue (three-fourths Brahman calves from Brahman-sired F dams Angus-sired F dams). Intramuscular adipocyte volume ( Angus cattle. Additionally, several differences were observed in i.m. adipose tissue that were consistent with this being a less-developed adipose

Extensive characterization and comparison of endothelial cells derived from dermis and adipose tissue : Potential use in tissue engineering

NARCIS (Netherlands)

Monsuur, H.N.; Weijers, E.M.; Niessen, F.B.; Gefen, A.; Koolwijk, P.; Gibbs, S.; van den Broek, L.J.

2016-01-01

Tissue-engineered constructs need to become quickly vascularized in order to ensure graft take. One way of achieving this is to incorporate endothelial cells (EC) into the construct. The adipose tissue stromal vascular fraction (adipose-SVF) might provide an alternative source for endothelial cells

Adipose tissue endocannabinoid system gene expression: depot differences and effects of diet and exercise

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Yang Rongze

2011-10-01

Full Text Available Abstract Background Alterations of endocannabinoid system in adipose tissue play an important role in lipid regulation and metabolic dysfunction associated with obesity. The purpose of this study was to determine whether gene expression levels of cannabinoid type 1 receptor (CB1 and fatty acid amide hydrolase (FAAH are different in subcutaneous abdominal and gluteal adipose tissue, and whether hypocaloric diet and aerobic exercise influence subcutaneous adipose tissue CB1 and FAAH gene expression in obese women. Methods Thirty overweight or obese, middle-aged women (BMI = 34.3 ± 0.8 kg/m2, age = 59 ± 1 years underwent one of three 20-week weight loss interventions: caloric restriction only (CR, N = 9, caloric restriction plus moderate-intensity aerobic exercise (CRM, 45-50% HRR, N = 13, or caloric restriction plus vigorous-intensity aerobic exercise (CRV, 70-75% HRR, N = 8. Subcutaneous abdominal and gluteal adipose tissue samples were collected before and after the interventions to measure CB1 and FAAH gene expression. Results At baseline, FAAH gene expression was higher in abdominal, compared to gluteal adipose tissue (2.08 ± 0.11 vs. 1.78 ± 0.10, expressed as target gene/β-actin mRNA ratio × 10-3, P Conclusions There are depot differences in subcutaneous adipose tissue endocannabinoid system gene expression in obese individuals. Aerobic exercise training may preferentially modulate abdominal adipose tissue endocannabinoid-related gene expression during dietary weight loss. Trial Registration ClinicalTrials.gov: NCT00664729.

Immune response in the adipose tissue of lean mice infected with the protozoan parasite Neospora caninum

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Teixeira, Luzia; Moreira, João; Melo, Joana; Bezerra, Filipa; Marques, Raquel M; Ferreirinha, Pedro; Correia, Alexandra; Monteiro, Mariana P; Ferreira, Paula G; Vilanova, Manuel

2015-01-01

The adipose tissue can make important contributions to immune function. Nevertheless, only a limited number of reports have investigated in lean hosts the immune response elicited in this tissue upon infection. Previous studies suggested that the intracellular protozoan Neospora caninum might affect adipose tissue physiology. Therefore, we investigated in mice challenged with this protozoan if immune cell populations within adipose tissue of different anatomical locations could be differently affected. Early in infection, parasites were detected in the adipose tissue and by 7 days of infection increased numbers of macrophages, regulatory T (Treg) cells and T-bet+ cells were observed in gonadal, mesenteric, omental and subcutaneous adipose tissue. Increased expression of interferon-γ was also detected in gonadal adipose tissue of infected mice. Two months after infection, parasite DNA was no longer detected in these tissues, but T helper type 1 (Th1) cell numbers remained above control levels in the infected mice. Moreover, the Th1/Treg cell ratio was higher than that of controls in the mesenteric and subcutaneous adipose tissue. Interestingly, chronically infected mice presented a marked increase of serum leptin, a molecule that plays a role in energy balance regulation as well as in promoting Th1-type immune responses. Altogether, we show that an apicomplexa parasitic infection influences immune cellular composition of adipose tissue throughout the body as well as adipokine production, still noticed at a chronic phase of infection when parasites were already cleared from that particular tissue. This strengthens the emerging view that infections can have long-term consequences for the physiology of adipose tissue. PMID:25581844

The effect of hypokinesia on lipid metabolism in adipose tissue

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Macho, Ladislav; Kvetn̆anský, Richard; Ficková, Mária

The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.

Insulin resistance, hepatic lipid and adipose tissue distribution in HIV infected men

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He, Qing; Engelson, Ellen S.; Ionescu, Gabriel; Glesby, Marshall J.; Albu, Jeanine B.; Kotler, Donald P.

2010-01-01

Background A large proportion of HIV-infected subjects on antiretroviral medication develop insulin resistance, especially in the context of fat redistribution. This study investigates the interrelationships among fat distribution, hepatic lipid content, and insulin resistance in HIV-infected men. Design and methods We performed a cross-sectional analysis of baseline data from twenty-three HIV-infected participants in 3 prospective clinical studies. Magnetic resonance spectroscopy was applied to quantify hepatic lipid concentrations. Magnetic resonance imaging was used to quantify whole body adipose tissue compartments, i.e., subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes as well as inter-muscular adipose tissue (IMAT) subcompartment, and omental-mesenteric adipose tissue (OMAT) and retroperitoneal adipose tissue (RPAT) subcompartments of VAT. Homeostasis model for assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin concentrations. Results Hepatic lipid content correlated significantly with total VAT (r=0.62, p=0.0014) but not with SAT (r=0.053, p=0.81). In univariate analysis, hepatic lipid content was associated with the OMAT (r=0.67, p=0.0004) and RPAT (r=0.53, p=0.009) subcompartments; HOMA-IR correlated with both VAT and hepatic lipid contents (r=0.61, p=0.057 and 0.68, p=0.0012, respectively). In stepwise linear regression models, hepatic lipid had the strongest associations with OMAT and with HOMA-IR. Conclusion Hepatic lipid content is associated with VAT volume, especially the omental-mesenteric subcompartment, in HIV-infected men. Hepatic lipid content is associated with insulin resistance in HIV-infected men. Hepatic lipid content might mediate the relationship between VAT and insulin resistance among treated, HIV-infected men. PMID:18572755

Insulin resistance, hepatic lipid and adipose tissue distribution in HIV-infected men.

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He, Qing; Engelson, Ellen S; Ionescu, Gabriel; Glesby, Marshall J; Albu, Jeanine B; Kotler, Donald P

2008-01-01

A large proportion of HIV-infected patients on antiretroviral medication develop insulin resistance, especially in the context of fat redistribution. This study investigates the interrelationships among fat distribution, hepatic lipid content, and insulin resistance in HIV-infected men. We performed a cross-sectional analysis of baseline data from 23 HIV-infected participants in three prospective clinical studies. Magnetic resonance spectroscopy was used to quantify hepatic lipid concentrations. Magnetic resonance imaging was used to quantify whole-body adipose tissue compartments: that is, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes, as well as the intermuscular adipose tissue (IMAT) subcompartment and the omental-mesenteric adipose tissue (OMAT) and retroperitoneal adipose tissue (RPAT) subcompartments of VAT. The homeostasis model for assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin concentrations. Hepatic lipid content correlated significantly with total VAT (r = 0.62, P = 0.0014), but not with SAT (r = 0.053, P = 0.81). In univariate analysis, hepatic lipid content was associated with the OMAT (r = 0.67, P = 0.0004) and RPAT (r = 0.53, P = 0.009) subcompartments; HOMA-IR correlated with both VAT and hepatic lipid contents (r = 0.61, P = 0.057 and r = 0.68, P = 0.0012, respectively). In stepwise linear regression models, hepatic lipid had the strongest associations with OMAT and with HOMA-IR. Hepatic lipid content is associated with VAT volume, especially the OMAT subcompartment, in HIV-infected men. Hepatic lipid content is associated with insulin resistance in HIV-infected men. Hepatic lipid content might mediate the relationship between VAT and insulin resistance among treated, HIV-infected men.

Lipid profiling of in vitro cell models of adipogenic differentiation: relationships with mouse adipose tissues

OpenAIRE

Liaw, Lucy; Prudovsky, Igor; Koza, Robert A.; Anunciado-Koza, Rea V.; Siviski, Matthew E.; Lindner, Volkhard; Friesel, Robert E.; Rosen, Clifford J.; Baker, Paul R.S.; Simons, Brigitte; Vary, Calvin P.H.

2016-01-01

Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MSALL. Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-...

The "Big Bang" in obese fat: Events initiating obesity-induced adipose tissue inflammation.

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Wensveen, Felix M; Valentić, Sonja; Šestan, Marko; Turk Wensveen, Tamara; Polić, Bojan

2015-09-01

Obesity is associated with the accumulation of pro-inflammatory cells in visceral adipose tissue (VAT), which is an important underlying cause of insulin resistance and progression to diabetes mellitus type 2 (DM2). Although the role of pro-inflammatory cytokines in disease development is established, the initiating events leading to immune cell activation remain elusive. Lean adipose tissue is predominantly populated with regulatory cells, such as eosinophils and type 2 innate lymphocytes. These cells maintain tissue homeostasis through the excretion of type 2 cytokines, such as IL-4, IL-5, and IL-13, which keep adipose tissue macrophages (ATMs) in an anti-inflammatory, M2-like state. Diet-induced obesity is associated with the loss of tissue homeostasis and development of type 1 inflammatory responses in VAT, characterized by IFN-γ. A key event is a shift of ATMs toward an M1 phenotype. Recent studies show that obesity-induced adipocyte hypertrophy results in upregulated surface expression of stress markers. Adipose stress is detected by local sentinels, such as NK cells and CD8(+) T cells, which produce IFN-γ, driving M1 ATM polarization. A rapid accumulation of pro-inflammatory cells in VAT follows, leading to inflammation. In this review, we provide an overview of events leading to adipose tissue inflammation, with a special focus on adipose homeostasis and the obesity-induced loss of homeostasis which marks the initiation of VAT inflammation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity

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Karen Nørgaard Nielsen

2018-05-01

Full Text Available Objective: The ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society. We speculate that nicotinamide adenine dinucleotide (NAD+ biosynthesis exemplifies this concept. Indeed NAD+/NADH metabolism in fat tissue has been previously linked with obesity, yet whether it plays a causal role in diet-induced adiposity is unknown. Here we investigated how the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT supports adipose plasticity and the pathological progression to obesity. Methods: We utilized a newly generated Nampt loss-of-function model to investigate the tissue-specific and systemic metabolic consequences of adipose NAD+ deficiency. Energy expenditure, glycemic control, tissue structure, and gene expression were assessed in the contexts of a high dietary fat burden as well as the transition back to normal chow diet. Results: Fat-specific Nampt knockout (FANKO mice were completely resistant to high fat diet (HFD-induced obesity. This was driven in part by reduced food intake. Furthermore, HFD-fed FANKO mice were unable to undergo healthy expansion of adipose tissue mass, and adipose depots were rendered fibrotic with markedly reduced mitochondrial respiratory capacity. Yet, surprisingly, HFD-fed FANKO mice exhibited improved glucose tolerance compared to control littermates. Removing the HFD burden largely reversed adipose fibrosis and dysfunction in FANKO animals whereas the improved glucose tolerance persisted. Conclusions: These findings indicate that adipose NAMPT plays an essential role in

Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue.

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Salas, Anna; Noé, Véronique; Ciudad, Carlos J; Romero, M Mar; Remesar, Xavier; Esteve, Montserrat

2007-08-28

Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFalpha) values showed overexpression (198%). Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism.

Dietary n-3 long-chain polyunsaturated fatty acids modify phosphoenolpyruvate carboxykinase activity and lipid synthesis from glucose in adipose tissue of rats fed a high-sucrose diet.

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Londero, Lisiane G; Rieger, Débora K; Hansen, Fernanda; Silveira, Simone L; Martins, Tiago L; Lulhier, Francisco; da Silva, Roselis S; Souza, Diogo O; Perry, Marcos L S; de Assis, Adriano M

2013-12-01

Long-chain polyunsaturated n-3 fatty acids (n-3 LCPUFAs) have hypolipidemic effects and modulate intermediary metabolism to prevent or reverse insulin resistance in a way that is not completely elucidated. Here, effects of these fatty acids on the lipid profile, phosphoenolpyruvate carboxykinase (PEPCK) activity, lipid synthesis from glucose in epididymal adipose tissue (Ep-AT) and liver were investigated. Male rats were fed a high-sucrose diet (SU diet), containing either sunflower oil or a mixture of sunflower and fish oil (SU-FO diet), and the control group was fed a standard diet. After 13 weeks, liver, adipose tissue and blood were harvested and analysed. The dietary n-3 LCPUFAs prevented sucrose-induced increase in adiposity and serum free fat acids, serum and hepatic triacylglycerol and insulin levels. Furthermore, these n-3 LCPUFAs decreased lipid synthesis from glucose and increased PEPCK activity in the Ep-AT of rats fed the SU-FO diet compared to those fed the SU diet, besides reducing lipid synthesis from glucose in hepatic tissue. Thus, the inclusion of n-3 LCPUFAs in the diet may be beneficial for the prevention or attenuation of dyslipidemia and insulin resistance, and for reducing the risk of related chronic diseases. Copyright © 2013 John Wiley & Sons, Ltd.

Adipose Tissue and Adrenal Glands: Novel Pathophysiological Mechanisms and Clinical Applications

OpenAIRE

Kargi, Atil Y.; Iacobellis, Gianluca

2014-01-01

Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unkn...

Adipose Tissue: Sanctuary for HIV/SIV Persistence and Replication.

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Pallikkuth, Suresh; Mohan, Mahesh

2015-12-01

This commentary highlights new findings from a recent study identifying adipose tissue as a potential HIV reservoir and a major site of inflammation during chronic human/simian immunodeficiency virus (HIV/SIV) infection. A concise discussion about upcoming challenges and new research avenues for reducing chronic adipose inflammation during HIV/SIV infection is presented. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adenovirus 36 DNA in Adipose Tissue of Patient with Unusual Visceral Obesity

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Salehian, Behrouz; Forman, Stephen J.; Kandeel, Fouad R.; Bruner, Denise E.; He, Jia

2010-01-01

Massive adipose tissue depositions in the abdomen and thorax sufficient to interfere with respiration developed in a patient with multiple medical problems. Biopsy of adipose tissue identified human adenovirus 36 (Adv 36) DNA. Adv 36 causes adipogenesis in animals and humans. Development of massive lipomatosis may be caused by Adv 36. PMID:20409382

Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice

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Adipose tissue macrophages play an important role in the pathogenesis of obese type 2 diabetes. High-fat diet-induced obesity has been shown to lead to adipose tissue macrophages accumulation in rodents;however, the impact of hyperglycemia on adipose tissue macrophages dynamics in high-fat diet-fed ...

Food consumption and adipose tissue DDT levels in Mexican women

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Marcia Galván-Portillo

2002-04-01

Full Text Available This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005 and residence in coastal areas (p = 0.002 and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body.

Food consumption and adipose tissue DDT levels in Mexican women

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Galván-Portillo Marcia

2002-01-01

Full Text Available This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005 and residence in coastal areas (p = 0.002 and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body.

Cryolipolysis for reduction of excess adipose tissue.

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Nelson, Andrew A; Wasserman, Daniel; Avram, Mathew M

2009-12-01

Controlled cold exposure has long been reported to be a cause of panniculitis in cases such as popsicle panniculitis. Cryolipolysis is a new technology that uses cold exposure, or energy extraction, to result in localized panniculitis and modulation of fat. Presently, the Zeltiq cryolipolysis device is FDA cleared for skin cooling, as well as various other indications, but not for lipolysis. There is, however, a pending premarket notification for noninvasive fat layer reduction. Initial animal and human studies have demonstrated significant reductions in the superficial fat layer thickness, ranging from 20% to 80%, following a single cryolipolysis treatment. The decrease in fat thickness occurs gradually over the first 3 months following treatment, and is most pronounced in patients with limited, discrete fat bulges. Erythema of the skin, bruising, and temporary numbness at the treatment site are commonly observed following treatment with the device, though these effects largely resolve in approximately 1 week. To date, there have been no reports of scarring, ulceration, or alterations in blood lipid or liver function profiles. Cryolipolysis is a new, noninvasive treatment option that may be of benefit in the treatment of excess adipose tissue.

Calcium sensing receptor as a novel mediator of adipose tissue dysfunction: mechanisms and potential clinical implications

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Roberto Bravo

2016-09-01

Full Text Available Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue is an active endocrine organ, with a crucial influence on whole-body homeostasis. White adipose tissue dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease and some cancers. Among the regulators of white adipose tissue physiology, the calcium-sensing receptor has arisen as a potential mediator of white adipose tissue dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that calcium-sensing receptor activation in the visceral (i.e. unhealthy white adipose tissue is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to calcium-sensing receptor activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in white adipose tissue plays a key role in the development of white adipose tissue dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that calcium-sensing receptor may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

Exenatide improves both hepatic and adipose tissue insulin resistance: A dynamic positron emission tomography study.

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Gastaldelli, Amalia; Gaggini, Melania; Daniele, Giuseppe; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Iozzo, Patricia

2016-12-01

Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1-RAs) act on multiple tissues, in addition to the pancreas. Recent studies suggest that GLP-1-RAs act on liver and adipose tissue to reduce insulin resistance (IR). Thus, we evaluated the acute effects of exenatide (EX) on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake. Fifteen male subjects (age = 56 ± 8 years; body mass index = 29 ± 1 kg/m 2 ; A1c = 5.7 ± 0.1%) were studied on two occasions, with a double-blind subcutaneous injection of EX (5 μg) or placebo (PLC) 30 minutes before a 75-g oral glucose tolerance test (OGTT). During OGTT, we measured hepatic (HGU) and adipose tissue (ATGU) glucose uptake with [ 18 F]2-fluoro-2-deoxy-D-glucose/positron emission tomography, lipolysis (RaGly) with [U- 2 H 5 ]-glycerol, oral glucose absorption (RaO) with [U- 13 C 6 ]-glucose, and hepatic glucose production (EGP) with [6,6- 2 H 2 ]-glucose. Adipo-IR and Hep-IR were calculated as (FFA 0-120min ) × (Ins 0-120min ) and (EGP 0-120min ) × (Ins 0-120min ), respectively. EX reduced RaO, resulting in reduced plasma glucose and insulin concentration from 0 to 120 minutes postglucose ingestion. EX decreased Hep-IR (197 ± 28 to 130 ± 37; P = 0.02) and increased HGU of orally administered glucose (23 ± 4 to 232 ± 89 [μmol/min/L]/[μmol/min/kg]; P = 0.003) despite lower insulin (23 ± 5 vs. 41 ± 5 mU/L; P < 0.02). EX enhanced insulin suppression of RaGly by decreasing Adipo-IR (23 ± 4 to 13 ± 3; P = 0.009). No significant effect of insulin was observed on ATGU (EX = 1.16 ± 0.15 vs. PLC = 1.36 ± 0.13 [μmol/min/L]/[μmol/min/kg]). Acute EX administration (1) improves Hep-IR, decreases EGP, and enhances HGU and (2) reduces Adipo-IR, improves the antilipolytic effect of insulin, and reduces plasma free fatty acid levels during OGTT. (Hepatology 2016;64:2028-2037). © 2016 by the American Association for the Study of Liver Diseases.

The fractionation of adipose tissue procedure to obtain stromal vascular fractions for regenerative purposes

NARCIS (Netherlands)

van Dongen, Joris A.; Stevens, Hieronymus P.; Parvizi, Mojtaba; van der Lei, Berend; Harmsen, Martin C.

2016-01-01

Autologous adipose tissue transplantation is clinically used to reduce dermal scarring and to restore volume loss. The therapeutic benefit on tissue damage more likely depends on the stromal vascular fraction of adipose tissue than on the adipocyte fraction. This stromal vascular fraction can be

Implication of low level inflammation in the insulin resistance of adipose tissue at late pregnancy.

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de Castro, J; Sevillano, J; Marciniak, J; Rodriguez, R; González-Martín, C; Viana, M; Eun-suk, O H; de Mouzon, S Hauguel; Herrera, E; Ramos, M P

2011-11-01

Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1β, plasminogen activator inhibitor-1, and TNF-α, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance.

Adipose tissue extracts plasma ammonia after sprint exercise in women and men

DEFF Research Database (Denmark)

Esbjörnsson, Mona; Bülow, Jens; Norman, Barbara

2006-01-01

This study evaluates a possible contribution of adipose tissue to the elimination of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men and women, repeated blood samples for plasma NH(3) analyses were obtained from brachial artery and from a subcutaneous abdominal vein......) with glutamate resulting in its conversion to glutamine. Adipose tissue may thus play an important physiological role in eliminating plasma NH(3) and thereby reducing the risk of NH(3) intoxication after high-intensity exercise.......This study evaluates a possible contribution of adipose tissue to the elimination of plasma ammonia (NH(3)) after high-intensity sprint exercise. In 14 healthy men and women, repeated blood samples for plasma NH(3) analyses were obtained from brachial artery and from a subcutaneous abdominal vein...... before and after three repeated 30-s cycle sprints separated by 20 min of recovery. Biopsies from subcutaneous abdominal adipose tissue were obtained and analyzed for glutamine and glutamate content. After exercise, both arterial and abdominal venous plasma NH(3) concentrations were lower in women than...

Weight loss independent changes in adipose tissue macrophage and T cell populations after sleeve gastrectomy in mice

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Henriette Frikke-Schmidt

2017-04-01

Full Text Available Objective: In addition to adipocytes, adipose tissue contains large numbers of immune cells. A wide range of evidence links the activity of these cells to regulation of adipocyte and systemic metabolic function. Bariatric surgery improves several aspects of metabolic derangements and at least some of these effects occur in a weight-loss independent manner. We sought to investigate the impact of vertical sleeve gastrectomy (VSG on adipose immune cell frequencies. Methods: We analyzed the frequencies of immune cells within distinct adipose tissue depots in obese mice that had VSG or sham surgery with a portion of the latter group pair-fed such that their body mass was matched to the VSG animals. Results: We demonstrate that VSG induced a shift in the epididymal adipose tissue leukocyte profile including increased frequencies of CD11c− macrophages, increased frequencies of T cells (CD4+, CD8+, and CD4−/CD8− T cells all increased, but a significantly decreased frequency of adipose tissue dendritic cells (ATDC that, despite the continued high fat feeding of the VSG group, dropped below control diet levels. Conclusions: These results indicate that VSG induces substantial changes in the immune populations residing in the adipose depots independent of weight loss. Author Video: Author Video Watch what authors say about their articles Keywords: Sleeve gastrectomy, Adipose tissue, Macrophages, T cells, Dendritic cells, Abbreviations: ATDC, adipose tissue dendritic cell, ATM, adipose tissue macrophage, eWAT, epididymal white adipose tissue, FFA, free fatty acids, HFS, high fat sham, iWAT, inguinal white adipose tissue, SVC, stromal vascular cells, VSG, vertical sleeve gastrectomy

Chromatin immunoprecipitation improvements for the processing of small frozen pieces of adipose tissue.

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Daniel Castellano-Castillo

Full Text Available Chromatin immunoprecipitation (ChIP has gained importance to identify links between the genome and the proteome. Adipose tissue has emerged as an active tissue, which secretes a wide range of molecules that have been related to metabolic and obesity-related disorders, such as diabetes, cardiovascular failure, metabolic syndrome, or cancer. In turn, epigenetics has raised the importance in discerning the possible relationship between metabolic disorders, lifestyle and environment. However, ChIP application in human adipose tissue is limited by several factors, such as sample size, frozen sample availability, high lipid content and cellular composition of the tissue. Here, we optimize the standard protocol of ChIP for small pieces of frozen human adipose tissue. In addition, we test ChIP for the histone mark H3K4m3, which is related to active promoters, and validate the performance of the ChIP by analyzing gene promoters for factors usually studied in adipose tissue using qPCR. Our improvements result in a higher performance in chromatin shearing and DNA recovery of adipocytes from the tissue, which may be useful for ChIP-qPCR or ChIP-seq analysis.

Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies

NARCIS (Netherlands)

Jurgens, W.J.F.M.; Oedayrajsingh-Varma, M.J.; Helder, M.N.; Zandieh Doulabi, B.; Schouten, T.E.; Kuik, D.J.; Ritt, M.J.P.F.; van Milligen-Kummer, F.J.

2008-01-01

The stromal vascular fraction (SVF) of adipose tissue contains an abundant population of multipotent adipose-tissue-derived stem cells (ASCs) that possess the capacity to differentiate into cells of the mesodermal lineage in vitro. For cell-based therapies, an advantageous approach would be to

Nonviral transfection of adipose tissue stromal cells: an experimental study.

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Lopatina, T V; Kalinina, N I; Parfyonova, E V

2009-04-01

Delivery of plasmid DNA and interfering RNA into adipose tissue stromal cells was carried out by the methods of lipofection, calcium phosphate method, and by electroporation. The percent of transfected cells after delivery of plasmid DNA by the calcium phosphate method and lipofection was 0 and 15%, respectively, vs. more than 50% after electroporation. Similar results were obtained for delivery of short-strand RNA into cells. These data indicate that electroporation is the most effective method of nonviral transfection of adipose tissue stromal cells.

Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner

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Forney, Laura A.; Lenard, Natalie R.; Stewart, Laura K.

2018-01-01

Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE) containing quercetin on subcutaneous (inguinal, IWAT) vs. visceral (epididymal, EWAT) white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 μg/day quercetin or high fat plus ROE containing 50 μg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms. PMID:29562620

Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner

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Laura A. Forney

2018-03-01

Full Text Available Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE containing quercetin on subcutaneous (inguinal, IWAT vs. visceral (epididymal, EWAT white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 μg/day quercetin or high fat plus ROE containing 50 μg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms.

Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology.

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Louveau, I; Perruchot, M-H; Bonnet, M; Gondret, F

2016-11-01

Both white and brown adipose tissues are recognized to be differently involved in energy metabolism and are also able to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Brown adipose tissue is predominant around birth, except in pigs. Irrespective of species, white adipose tissue has a large capacity to expand postnatally and is able to adapt to a variety of factors. The aim of this review is to update the cellular and molecular mechanisms associated with pre- and postnatal adipose tissue development with a special focus on pigs and ruminants. In contrast to other tissues, the embryonic origin of adipose cells remains the subject of debate. Adipose cells arise from the recruitment of specific multipotent stem cells/progenitors named adipose tissue-derived stromal cells. Recent studies have highlighted the existence of a variety of those cells being able to differentiate into white, brown or brown-like/beige adipocytes. After commitment to the adipocyte lineage, progenitors undergo large changes in the expression of many genes involved in cell cycle arrest, lipid accumulation and secretory functions. Early nutrition can affect these processes during fetal and perinatal periods and can also influence or pre-determinate later growth of adipose tissue. How these changes may be related to adipose tissue functional maturity around birth and can influence newborn survival is discussed. Altogether, a better knowledge of fetal and postnatal adipose tissue development is important for various aspects of animal production, including neonatal survival, postnatal growth efficiency and health.

Effects of a physiological GH pulse on interstitial glycerol in abdominal and femoral adipose tissue

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Gravhølt, C H; Schmitz, Ole; Simonsen, L

1999-01-01

.0005). Administration of GH induced an increase in interstitial glycerol in both abdominal and femoral adipose tissue (ANOVA: abdominal, P = 0. 04; femoral, P = 0.03). There was no overall difference in the response to GH in the two regions during the study period as a whole (ANOVA: P = 0.5), but during peak...... stimulation of lipolysis abdominal adipose tissue was, in absolute but not in relative terms, stimulated more markedly than femoral adipose tissue (ANOVA: P = 0. 03 from 45 to 225 min). Peak interstitial glycerol values of 253 +/- 37 and 336 +/- 74 micromol/l were seen after 135 and 165 min in femoral...... and abdominal adipose tissue, respectively. ATBF was not statistically different in the two situations (ANOVA: P = 0.7). In conclusion, we have shown that a physiological pulse of GH increases interstitial glycerol concentrations in both femoral and abdominal adipose tissue, indicating activated lipolysis...

Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

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Gunawardana, Subhadra C.; Piston, David W.

2012-01-01

Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized gluco...

Brain–gut–adipose-tissue communication pathways at a glance

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Chun-Xia Yi

2012-09-01

Full Text Available One of the ‘side effects’ of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain’s survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure. Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders.

Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue

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Remesar Xavier

2007-08-01

Full Text Available Abstract Background Short-term OE (oleoyl-estrone treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results Gene expression in adipose tissue from female treated rats (48 hours was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL were decreased by 52%, those of Fatty Acid Synthase (FAS by 95%, those of Hormone Sensible Lipase (HSL by 32%, those of Acetyl CoA Carboxylase (ACC by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b by 45%, and those of Fatty Acid Transport Protein 1 (FATP1 and Adipocyte Fatty Acid Binding Protein (FABP4 by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFα values showed overexpression (198%. Conclusion Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism.

Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

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Aimee L. Dordevic

2015-07-01

Full Text Available Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD; body mass index (BMI 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water, carbohydrate (maltodextrin or lipid (dairy-cream. Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h, as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1, interleukin 6 (IL-6 and tumor necrosis factor-α (TNF-α increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03 and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001 decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

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

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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.

Tissue-specific congener composition of organohalogen and metabolite contaminants in East Greenland polar bears (Ursus maritimus)

International Nuclear Information System (INIS)

Gebbink, Wouter A.; Sonne, Christian; Dietz, Rune; Kirkegaard, Maja; Riget, Frank F.; Born, Erik W.; Muir, Derek C.G.; Letcher, Robert J.

2008-01-01

Congener patterns of the major organohalogen contaminant classes of PCBs, PBDEs and their metabolites and/or by-products (OH-PCBs, MeSO 2 -PCBs, OH-PBDEs and MeO-PBDEs) were examined in adipose tissue, liver, brain and blood of East Greenland polar bears (Ursus maritimus). PCB, OH-PCB, MeSO 2 -PCB and PBDE congener patterns showed significant differences (p ≤ 0.05) mainly in the liver and the brain relative to the adipose tissue and the blood. OH-PBDEs and MeO-PBDEs were not detected in the brain and liver, but had different patterns in blood versus the adipose tissue. Novel OH-polybrominated biphenyls (OH-PBBs), one tri- and two tetra-brominated OH-PBBs were detected in all tissues and blood. Congener pattern differences among tissues and blood are likely due to a combination of factors, e.g., biotransformation and retention in the liver, retention in the blood and blood-brain barrier transport. Our findings suggest that different congener pattern exposures to these classes of contaminants should be considered with respect to potential target tissue-specific effects in East Greenland polar bears. - Tissues-specific (adipose tissue, liver, brain and blood) differences exist for the congener patterns of PCBs, PBDEs and their metabolites/degradation products in East Greenland polar bears

Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue

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Sofia Dias

2018-01-01

Full Text Available Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis characterized by visceral obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance. The growing prevalence of metabolic syndrome will certainly contribute to the burden of cardiovascular disease. Obesity and dyslipidemia are main features of metabolic syndrome, and both can present with adipose tissue dysfunction, involved in the pathogenic mechanisms underlying this syndrome. We revised the effects, and underlying mechanisms, of the current approved drugs for dyslipidemia and obesity (fibrates, statins, niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion, phentermine/topiramate, bupropion and naltrexone, and liraglutide on adipose tissue. Specifically, we explored how these drugs can modulate the complex pathways involved in metabolism, inflammation, atherogenesis, insulin sensitivity, and adipogenesis. The clinical outcomes of adipose tissue modulation by these drugs, as well as differences of major importance for clinical practice between drugs of the same class, were identified. Whether solutions to these issues will be found in further adjustments and combinations between drugs already in use or necessarily in new advances in pharmacology is not known. To better understand the effect of drugs used in dyslipidemia and obesity on adipose tissue not only is challenging for physicians but could also be the next step to tackle cardiovascular disease.

Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.

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Findeisen, Hannes M; Pearson, Kevin J; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L; Cohn, Dianne; Heywood, Elizabeth B; de Cabo, Rafael; Bruemmer, Dennis

2011-04-14

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G(1)→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction.

Ontogenesis of muscle and adipose tissues and their interactions in ruminants and other species.

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Bonnet, M; Cassar-Malek, I; Chilliard, Y; Picard, B

2010-07-01

The lean-to-fat ratio, that is, the relative masses of muscle and adipose tissue, is a criterion for the yield and quality of bovine carcasses and meat. This review describes the interactions between muscle and adipose tissue (AT) that may regulate the dynamic balance between the number and size of muscle v. adipose cells. Muscle and adipose tissue in cattle grow by an increase in the number of cells (hyperplasia), mainly during foetal life. The total number of muscle fibres is set by the end of the second trimester of gestation. By contrast, the number of adipocytes is never set. Number of adipocytes increases mainly before birth until 1 year of age, depending on the anatomical location of the adipose tissue. Hyperplasia concerns brown pre-adipocytes during foetal life and white pre-adipocytes from a few weeks after birth. A decrease in the number of secondary myofibres and an increase in adiposity in lambs born from mothers severely underfed during early pregnancy suggest a balance in the commitment of a common progenitor into the myogenic or adipogenic lineages, or a reciprocal regulation of the commitment of two distinct progenitors. The developmental origin of white adipocytes is a subject of debate. Molecular and histological data suggested a possible transdifferentiation of brown into white adipocytes, but this hypothesis has now been challenged by the characterization of distinct precursor cells for brown and white adipocytes in mice. Increased nutrient storage in fully differentiated muscle fibres and adipocytes, resulting in cell enlargement (hypertrophy), is thought to be the main mechanism, whereby muscle and fat masses increase in growing cattle. Competition or prioritization between adipose and muscle cells for the uptake and metabolism of nutrients is suggested, besides the successive waves of growth of muscle v. adipose tissue, by the inhibited or delayed adipose tissue growth in bovine genotypes exhibiting strong muscular development. This

Involvement of Visceral Adipose Tissue in Immunological Modulation of Inflammatory Cascade in Preeclampsia

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Katsuhiko Naruse

2015-01-01

Full Text Available Objectives. The pathophysiology of preeclampsia is characterized by abnormal placentation, an exaggerated inflammatory response, and generalized dysfunction of the maternal endothelium. We investigated the effects of preeclampsia serum on the expression of inflammation-related genes by adipose tissue. Materials and Methods. Visceral adipose tissue was obtained from the omentum of patients with early ovarian cancer without metastasis. Adipose tissue was incubated with sera obtained from either five women affected with severe preeclampsia or five women from control pregnant women at 37°C in a humidified incubator at 5% CO2 for 24 hours. 370 genes in total mRNA were analyzed with quantitative RT-PCR (Inflammatory Response & Autoimmunity gene set. Results. Gene expression analysis revealed changes in the expression levels of 30 genes in adipose tissue treated with preeclampsia sera. Some genes are related to immune response, oxidative stress, insulin resistance, and adipogenesis, which plays a central role in excessive systemic inflammatory response of preeclampsia. In contrast, other genes have shown beneficial effects in the regulation of Th2 predominance, antioxidative stress, and insulin sensitivity. Conclusion. In conclusion, visceral adipose tissue offers protection against inflammation, oxidative insults, and other forms of cellular stress that are central to the pathogenesis of preeclampsia.

Adrenal gland volume, intra-abdominal and pericardial adipose tissue in major depressive disorder.

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Kahl, Kai G; Schweiger, Ulrich; Pars, Kaweh; Kunikowska, Alicja; Deuschle, Michael; Gutberlet, Marcel; Lichtinghagen, Ralf; Bleich, Stefan; Hüper, Katja; Hartung, Dagmar

2015-08-01

Major depressive disorder (MDD) is associated with an increased risk for the development of cardio-metabolic diseases. Increased intra-abdominal (IAT) and pericardial adipose tissue (PAT) have been found in depression, and are discussed as potential mediating factors. IAT and PAT are thought to be the result of a dysregulation of the hypothalamus-pituitary-adrenal axis (HPAA) with subsequent hypercortisolism. Therefore we examined adrenal gland volume as proxy marker for HPAA activation, and IAT and PAT in depressed patients. Twenty-seven depressed patients and 19 comparison subjects were included in this case-control study. Adrenal gland volume, pericardial, intraabdominal and subcutaneous adipose tissue were measured by magnetic resonance imaging. Further parameters included factors of the metabolic syndrome, fasting cortisol, fasting insulin, and proinflammatory cytokines. Adrenal gland and pericardial adipose tissue volumes, serum concentrations of cortisol and insulin, and serum concentrations tumor-necrosis factor-α were increased in depressed patients. Adrenal gland volume was positively correlated with intra-abdominal and pericardial adipose tissue, but not with subcutaneous adipose tissue. Our findings point to the role of HPAA dysregulation and hypercortisolism as potential mediators of IAT and PAT enlargement. Further studies are warranted to examine whether certain subtypes of depression are more prone to cardio-metabolic diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

A role of low dose chemical mixtures in adipose tissue in carcinogenesis.

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Lee, Duk-Hee; Jacobs, David R; Park, Ho Yong; Carpenter, David O

2017-11-01

The Halifax project recently hypothesized a composite carcinogenic potential of the mixture of low dose chemicals which are commonly encountered environmentally, yet which are not classified as human carcinogens. A long neglected but important fact is that adipose tissue is an important exposure source for chemical mixtures. In fact, findings from human studies based on several persistent organic pollutants in general populations with only background exposure should be interpreted from the viewpoint of chemical mixtures because serum concentrations of these chemicals can be seen as surrogates for chemical mixtures in adipose tissue. Furthermore, in conditions such as obesity with dysfunctional adipocytes or weight loss in which lipolysis is increased, the amount of the chemical mixture released from adipose tissue to circulation is increased. Thus, both obesity and weight loss can enhance the chance of chemical mixtures reaching critical organs, however paradoxical this idea may be when fat mass is the only factor considered. The complicated, interrelated dynamics of adipocytes and chemical mixtures can explain puzzling findings related to body weight among cancer patients, including the obesity paradox. The contamination of fat in human diet with chemical mixtures, occurring for reasons similar to contamination of human adipose tissue, may be a missing factor which affects the association between dietary fat intake and cancer. The presence of chemical mixtures in adipose tissue should be considered in future cancer research, including clinical trials on weight management among cancer survivors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Minimally invasive collection of adipose tissue facilitates the study of eco-physiology in small-bodied mammals

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Jeff Clerc; Theodore J. Weller; Jeffrey B. Schineller; Joseph M. Szewczak; Diana Fisher

2016-01-01

Adipose tissue is the primary fuel storage for vertebrates and is an important component of energy budgets during periods of peak energetic demands. Investigating the composition of adipose tissue can provide information about energetics, migration, reproduction, and other life-history traits. Until now, most field methods for sampling the adipose tissue of...

ABCD2 identifies a subclass of peroxisomes in mouse adipose tissue

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Liu, Xiaoxi, E-mail: xiaoxi.liu@uky.edu; Liu, Jingjing, E-mail: jingjing.liu0@gmail.com; Lester, Joshua D., E-mail: joshua.lester@uky.edu; Pijut, Sonja S., E-mail: srhee2@uky.edu; Graf, Gregory A., E-mail: Gregory.Graf@uky.edu

2015-01-02

Highlights: • We examined the D2 localization and the proteome of D2-containing compartment in mouse adipose tissue. • We confirmed the presence of D2 on a subcellular compartment that has typical structure as a microperoxisome. • We demonstrated the scarcity of peroxisome markers on D2-containing compartment. • The D2-containing compartment may be a subpopulation of peroxisome in mouse adipose tissue. • Proteomic data suggests potential association between D2-containing compartment and mitochondria and ER. - Abstract: ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Both D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ∼200 nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER.

Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats.

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Amin, Mohamed M; Arbid, Mahmoud S

2017-02-01

Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.

Consumption of resistant starch decreases postprandial lipogenesis in white adipose tissue of the rat

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Brown Marc A

2006-09-01

Full Text Available Abstract Chronic consumption of diets high in resistant starch (RS leads to reduced fat cell size compared to diets high in digestible starch (DS in rats and increases total and meal fat oxidation in humans. The aim of the present study was to examine the rate of lipogenesis in key lipogenic organs following a high RS or DS meal. Following an overnight fast, male Wistar rats ingested a meal with an RS content of 2% or 30% of total carbohydrate and were then administered an i.p bolus of 50 μCi 3H2O either immediately or 1 hour post-meal. One hour following tracer administration, rats were sacrificed, a blood sample collected, and the liver, white adipose tissue (WAT, and gastrocnemius muscle excised and frozen until assayed for total 3H-lipid and 3H-glycogen content. Plasma triglyceride and NEFA concentrations and 3H-glycogen content did not differ between groups. In all tissues, except the liver, there was a trend for the rate of lipogenesis to be higher in the DS group than the RS group which reached significance only in WAT at 1 h (p

Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

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Abderaouf Damouche

2015-09-01

Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

11Beta-HSD type 1 expression in human adipose tissue: impact of gender, obesity, and fat localization

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Paulsen, Søren Kildeberg; Pedersen, Steen Bønløkke; Fisker, Sanne

2007-01-01

of the metabolic syndrome. Our objective was to compare 11beta-HSD1 gene expression in different fat depots (visceral, subcutaneous abdominal, and subcutaneous gluteal) in lean and obese men and women. RESEARCH METHODS AND PROCEDURES: A cross-sectional study design was used for healthy patients undergoing minor...... women had lower 11beta-HSD1 gene expression in subcutaneous adipose tissue compared with men (62% lower, p difference was found between obese men and women. 11Beta-HSD1 mRNA in human adipose tissue was higher in obese subjects compared with lean subjects in both women...... and men and in both subcutaneous and visceral adipose tissue. No difference in mRNA expression of 11beta-HSD1 between visceral and subcutaneous adipose tissue or between subcutaneous adipose tissue from different depots was found. CONCLUSIONS: 11Beta-HSD1 in adipose tissue is increased in obesity in both...

Remodeling of adipose tissue at experimental diabetes mellitus

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O. A. Konovalova

2013-08-01

Full Text Available Introduction Diabetes mellitus (DM type 1 is chronіc disease whith progressive selective destruction of β- cells pancreatic islets (of Langerhans and whith development of absolute insulin failure. Active immune mechanisms take part in pathogenesis of this disease. Recently many publication appeared which report about the role of adipose tissue. In such way adipose tissue is not only the main metabolic regulator and endocrine organ synthesizing more than 30 regulatory proteins- adipokines, but it is one of the organs of immune system. Dysregulation of adipose tissue leads to morphological restructuring- remodeling of adipocytes, and the development of inflammation of adipose tissue in its turn is integral component of progression of many diseases. The aim of research The aim of this study was to investigate the morphological and functional state of parapancreatic fibre adipocytes in male Wistar rats in experimental diabetes mellitus. Materials and methods The study has been carried out on 20 male Wistar rats with weight 115-135 g. The animals were divided into 2 groups. The control group, which were injected 0,5 ml 0,1 М citrate buffer intraperitoneally (1group. Rats with 7 day experimental streptozotocin-induced diabetes mellitus were in the 2nd group. Adipose tissue was examined on the seventh day. For histological examination sections were colored with haematoxylin and eosin. Images were taken by using a fluorescence microscope PrimoStar(ZEISS,Germany with a computer-assisted video system AxioCam 5c (ZEISS,Germany including the NIH-Image software (NIH Image version 1·46. All statistical analyses were performed using EXCEL MS Office 2010 (Microsoft Corp., USA, STATISTICA 6.0 (Stat-Soft, 2001 software. Results were expressed as mean values ± SEM. Differences were considered statistically significant if the p value was <0.05. Results Injection of streptozotocin to experimental animals led to the development of experimental diabetes mellitus

Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo

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Bülow, J; Madsen, J; Astrup, A

1985-01-01

Subcutaneous or perirenal adipose tissue blood flow was measured with the 133Xe-washout technique before and after intravenous injection or infusion of Intralipid in six anesthetized, otherwise intact mongrel dogs. In four anesthetized mongrel puppies adipose tissue blood flow was measured...... as well as in young dogs after this treatment. The administration of Intralipid did not per se induce the vasoconstriction. The vasoconstriction took place simultaneously with increasing FFA/albumin molar ratios. The results support our previous findings in perfused fat pads that high molar FFA....../albumin ratios increase vascular resistance in adipose tissue and they give further support to our suggestion that this vasoconstriction may be a link in a negative-feedback mechanism regulating FFA-mobilization in relation to FFA utilization....

Endoplasmic reticulum stress is increased in adipose tissue of women with gestational diabetes.

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Stella Liong

Full Text Available Maternal obesity and gestational diabetes mellitus (GDM are two increasingly common and important obstetric complications that are associated with severe long-term health risks to mothers and babies. IL-1β, which is increased in obese and GDM pregnancies, plays an important role in the pathophysiology of these two pregnancy complications. In non-pregnant tissues, endoplasmic (ER stress is increased in diabetes and can induce IL-1β via inflammasome activation. The aim of this study was to determine whether ER stress is increased in omental adipose tissue of women with GDM, and if ER stress can also upregulate inflammasome-dependent secretion of IL-1β. ER stress markers IRE1α, GRP78 and XBP-1s were significantly increased in adipose tissue of obese compared to lean pregnant women. ER stress was also increased in adipose tissue of women with GDM compared to BMI-matched normal glucose tolerant (NGT women. Thapsigargin, an ER stress activator, induced upregulated secretion of mature IL-1α and IL-1β in human omental adipose tissue explants primed with bacterial endotoxin LPS, the viral dsRNA analogue poly(I:C or the pro-inflammatory cytokine TNF-α. Inhibition of capase-1 with Ac-YVAD-CHO resulted in decreased IL-1α and IL-1β secretion, whereas inhibition of pannexin-1 with carbenoxolone suppressed IL-1β secretion only. Treatment with anti-diabetic drugs metformin and glibenclamide also reduced IL-1α and IL-1β secretion in infection and cytokine-primed adipose tissue. In conclusion, this study has demonstrated ER stress to activate the inflammasome in pregnant adipose tissue. Therefore, increased ER stress may contribute towards the pathophysiology of obesity in pregnancy and GDM.

Impact of Perturbed Pancreatic β-Cell Cholesterol Homeostasis on Adipose Tissue and Skeletal Muscle Metabolism

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Cochran, Blake J.; Hou, Liming; Manavalan, Anil Paul Chirackal; Moore, Benjamin M.; Tabet, Fatiha; Sultana, Afroza; Cuesta Torres, Luisa; Tang, Shudi; Shrestha, Sudichhya; Senanayake, Praween; Patel, Mili; Ryder, William J.; Bongers, Andre; Maraninchi, Marie; Wasinger, Valerie C.; Westerterp, Marit; Tall, Alan R.; Barter, Philip J.

2016-01-01

Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high-glucose conditions, and glucose disposal was shifted from skeletal muscle to adipose tissue. The β-DKO mice also had increased body fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP-1 levels, and decreased skeletal muscle mass. They were not, however, insulin resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not the systemic inflammation or increased adipose tissue macrophage content, were reversed when plasma insulin levels were normalized by insulin supplementation. These studies identify a mechanism by which perturbation of β-cell cholesterol homeostasis and impaired insulin secretion increase adiposity, reduce skeletal muscle mass, and cause systemic inflammation. They further identify β-cell dysfunction as a potential therapeutic target in people at increased risk of developing type 2 diabetes. PMID:27702832

Ex-Vivo Tissues Engineering Modeling for Reconstructive Surgery Using Human Adult Adipose Stem Cells and Polymeric Nanostructured Matrix.

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Morena, Francesco; Argentati, Chiara; Calzoni, Eleonora; Cordellini, Marino; Emiliani, Carla; D'Angelo, Francesco; Martino, Sabata

2016-03-31

The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA ® Meshed Bilayer Wound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells.

Diet-induced changes in subcutaneous adipose tissue blood flow in man

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Simonsen, L; Bülow, J; Astrup, A

1990-01-01

The effect of a carbohydrate-rich meal on subcutaneous adipose tissue blood flow was studied with and without continuous i.v. infusion of propranolol in healthy volunteers. The subcutaneous adipose tissue blood flow was measured with the 133Xe washout method in three different locations......: the forearm, the thigh and the abdomen. The subjects were given a meal consisting of white bread, jam, honey and apple juice (about 2300 kJ). The meal induced a twofold increase in blood flow in the examined tissues. Propranolol abolished the flow increase in the thigh and the abdomen and reduced...

Glucose-dependent insulinotropic polypeptide has impaired effect on abdominal, subcutaneous adipose tissue metabolism in obese subjects

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Asmar, M; Simonsen, L; Arngrim, N

2013-01-01

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) appears to have a role in lipid metabolism. Recently, we showed that GIP in combination with hyperinsulinemia and hyperglycemia increases triglyceride uptake in abdominal, subcutaneous adipose tissue in lean humans. It has been suggested...... that increased GIP secretion in obesity will promote lipid deposition in adipose tissue. In light of the current attempts to employ GIP antagonists in the treatment and prevention of human obesity, the present experiments were performed in order to elucidate whether the adipose tissue lipid metabolism would...... to an oral glucose challenge: (i) NGT and (ii) IGT. Abdominal, subcutaneous adipose tissue lipid metabolism was studied by conducting measurements of arteriovenous concentrations of metabolites and regional adipose tissue blood flow (ATBF) during GIP (1.5 pmol kg(-1) min(-1)) in combination with a HI...

Technical note: Alternatives to reduce adipose tissue sampling bias.

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Cruz, G D; Wang, Y; Fadel, J G

2014-10-01

Understanding the mechanisms by which nutritional and pharmaceutical factors can manipulate adipose tissue growth and development in production animals has direct and indirect effects in the profitability of an enterprise. Adipocyte cellularity (number and size) is a key biological response that is commonly measured in animal science research. The variability and sampling of adipocyte cellularity within a muscle has been addressed in previous studies, but no attempt to critically investigate these issues has been proposed in the literature. The present study evaluated 2 sampling techniques (random and systematic) in an attempt to minimize sampling bias and to determine the minimum number of samples from 1 to 15 needed to represent the overall adipose tissue in the muscle. Both sampling procedures were applied on adipose tissue samples dissected from 30 longissimus muscles from cattle finished either on grass or grain. Briefly, adipose tissue samples were fixed with osmium tetroxide, and size and number of adipocytes were determined by a Coulter Counter. These results were then fit in a finite mixture model to obtain distribution parameters of each sample. To evaluate the benefits of increasing number of samples and the advantage of the new sampling technique, the concept of acceptance ratio was used; simply stated, the higher the acceptance ratio, the better the representation of the overall population. As expected, a great improvement on the estimation of the overall adipocyte cellularity parameters was observed using both sampling techniques when sample size number increased from 1 to 15 samples, considering both techniques' acceptance ratio increased from approximately 3 to 25%. When comparing sampling techniques, the systematic procedure slightly improved parameters estimation. The results suggest that more detailed research using other sampling techniques may provide better estimates for minimum sampling.

Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

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Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

2015-12-01

Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Hypoxia Enhances Differentiation of Adipose Tissue-Derived Stem Cells toward the Smooth Muscle Phenotype

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Fang Wang

2018-02-01

Full Text Available Smooth muscle differentiated adipose tissue-derived stem cells are a valuable resource for regeneration of gastrointestinal tissues, such as the gut and sphincters. Hypoxia has been shown to promote adipose tissue-derived stem cells proliferation and maintenance of pluripotency, but the influence of hypoxia on their smooth myogenic differentiation remains unexplored. This study investigated the phenotype and contractility of adipose-derived stem cells differentiated toward the smooth myogenic lineage under hypoxic conditions. Oxygen concentrations of 2%, 5%, 10%, and 20% were used during differentiation of adipose tissue-derived stem cells. Real time reverse transcription polymerase chain reaction and immunofluorescence staining were used to detect the expression of smooth muscle cells-specific markers, including early marker smooth muscle alpha actin, middle markers calponin, caldesmon, and late marker smooth muscle myosin heavy chain. The specific contractile properties of cells were verified with both a single cell contraction assay and a gel contraction assay. Five percent oxygen concentration significantly increased the expression levels of α-smooth muscle actin, calponin, and myosin heavy chain in adipose-derived stem cell cultures after 2 weeks of induction (p < 0.01. Cells differentiated in 5% oxygen conditions showed greater contraction effect (p < 0.01. Hypoxia influences differentiation of smooth muscle cells from adipose stem cells and 5% oxygen was the optimal condition to generate smooth muscle cells that contract from adipose stem cells.

Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population

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Jun Zhang

2015-01-01

Full Text Available Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P<0.01. The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-α and MCP-1 in normal group were lower than those in obesity and T2DM groups (P<0.01. In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue.

Integrative systems analysis of diet-induced obesity identified a critical transition in the transcriptomes of the murine liver and epididymal white adipose tissue.

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Kim, J; Kwon, E-Y; Park, S; Kim, J-R; Choi, S-W; Choi, M-S; Kim, S-J

2016-02-01

It is well known that high-fat diet (HFD) can cause immune system-related pathological alterations after a significant body weight gain. The mechanisms of the delayed pathological alterations during the development of diet-induced obesity (DIO) are not fully understood. To elucidate the mechanisms underlying DIO development, we analyzed time-course microarray data obtained from a previous study. First, differentially expressed genes (DEGs) were identified at each time point by comparing the hepatic transcriptome of mice fed HFD with that of mice fed normal diet. Next, we clustered the union of DEGs and identified annotations related to each cluster. Finally, we constructed an 'integrated obesity-associated gene regulatory network (GRN) in murine liver'. We analyzed the epididymal white adipose tissue (eWAT) transcriptome usig the same procedure. Based on time-course microarray data, we found that the genes associated with immune responses were upregulated with an oscillating expression pattern between weeks 2 and 8, relatively downregulated between weeks 12 and 16, and eventually upregulated after week 20 in the liver of the mice fed HFD. The genes associated with immune responses were also upregulated at late stage, in the eWAT of the mice fed HFD. These results suggested that a critical transition occurred in the immune system-related transcriptomes of the liver and eWAT around week 16 of the DIO development, and this may be associated with the delayed pathological alterations. The GRN analysis suggested that Maff may be a key transcription factor for the immune system-related critical transition thatoccurred at week 16. We found that transcription factors associated with immune responses were centrally located in the integrated obesity-associated GRN in the liver. In this study, systems analysis identified regulatory network modules underlying the delayed immune system-related pathological changes during the development of DIO and could suggest possible

Quantification of intermuscular and intramuscular adipose tissue using magnetic resonance imaging after neurodegenerative disorders

Institute of Scientific and Technical Information of China (English)

Madoka Ogawa; Robert Lester; Hiroshi Akima; Ashraf S. Gorgey

2017-01-01

Ectopic adiposity has gained considerable attention because of its tight association with metabolic and cardiovascular health in persons with spinal cord injury (SCI). Ectopic adiposity is characterized by the storage of adipose tissue in non-subcutaneous sites. Magnetic resonance imaging (MRI) has proven to be an effective tool in quantifying ectopic adiposity and provides the opportunity to measure different adipose depots including intermuscular adipose tissue (IMAT) and intramuscular adipose tissue (IntraMAT) or in-tramuscular fat (IMF). It is highly important to distinguish and clearly define these compartments, because controversy still exists on how to accurately quantify these adipose depots. Investigators have relied on separating muscle from fat pixels based on their characteristic signal intensities. A common technique is plotting a threshold histogram that clearly separates between muscle and fat peaks. The cut-offs to separate between muscle and fat peaks are still not clearly defined and different cut-offs have been identified. This review will outline and compare the Midpoint and Otsu techniques, two methods used to determine the threshold between muscle and fat pixels on T1 weighted MRI. The process of water/fat segmentation using the Dixon method will also be outlined. We are hopeful that this review will trigger more research towards accurately quantifying ectopic adiposity due to its high relevance to cardiometabolic health after SCI.

A low-protein, high-carbohydrate diet increases browning in perirenal adipose tissue but not in inguinal adipose tissue.

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Pereira, Mayara P; Ferreira, Laís A A; da Silva, Flávia H S; Christoffolete, Marcelo A; Metsios, George S; Chaves, Valéria E; de França, Suélem A; Damazo, Amílcar S; Flouris, Andreas D; Kawashita, Nair H

2017-10-01

The aim of this study was to evaluate the browning and origin of fatty acids (FAs) in the maintenance of triacylglycerol (TG) storage and/or as fuel for thermogenesis in perirenal adipose tissue (periWAT) and inguinal adipose tissue (ingWAT) of rats fed a low-protein, high-carbohydrate (LPHC) diet. LPHC (6% protein, 74% carbohydrate) or control (C; 17% protein, 63% carbohydrate) diets were administered to rats for 15 d. The tissues were stained with hematoxylin and eosin for histologic analysis. The content of uncoupling protein 1 (UCP1) was determined by immunofluorescence. Levels of T-box transcription factor (TBX1), PR domain containing 16 (PRDM16), adipose triacylglycerol lipase (ATGL), hormone-sensitive lipase, lipoprotein lipase (LPL), glycerokinase, phosphoenolpyruvate carboxykinase (PEPCK), glucose transporter 4, β 3 -adrenergic receptor (AR), β 1 -AR, protein kinase A (PKA), adenosine-monophosphate-activated protein kinase (AMPK), and phospho-AMPK were determined by immunoblotting. Serum fibroblast growth factor 21 (FGF21) was measured using a commercial kit (Student's t tests, P diet increased FGF21 levels by 150-fold. The presence of multilocular adipocytes, combined with the increased contents of UCP1, TBX1, and PRDM16 in periWAT of LPHC-fed rats, suggested the occurrence of browning. The contents of β 1 -AR and LPL were increased in the periWAT. The ingWAT showed higher ATGL and PEPCK levels, phospho-AMPK/AMPK ratio, and reduced β 3 -AR and PKA levels. These findings suggest that browning occurred only in the periWAT and that higher utilization of FAs from blood lipoproteins acted as fuel for thermogenesis. Increased glycerol 3-phosphate generation by glyceroneogenesis increased FAs reesterification from lipolysis, explaining the increased TG storage in the ingWAT. Copyright © 2017 Elsevier Inc. All rights reserved.

Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

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Tsoli, Maria; Swarbrick, Michael M; Robertson, Graham R

2016-06-01

Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Brown Adipose Tissue Bioenergetics: A New Methodological Approach

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Calderon‐Dominguez, María; Alcalá, Martín; Sebastián, David; Zorzano, Antonio; Viana, Marta; Serra, Dolors

2017-01-01

The rediscovery of brown adipose tissue (BAT) in humans and its capacity to oxidize fat and dissipate energy as heat has put the spotlight on its potential as a therapeutic target in the treatment of several metabolic conditions including obesity and diabetes. To date the measurement of bioenergetics parameters has required the use of cultured cells or extracted mitochondria with the corresponding loss of information in the tissue context. Herein, we present a method to quantify mitochondrial bioenergetics directly in BAT. Based on XF Seahorse Technology, we assessed the appropriate weight of the explants, the exact concentration of each inhibitor in the reaction, and the specific incubation time to optimize bioenergetics measurements. Our results show that BAT basal oxygen consumption is mostly due to proton leak. In addition, BAT presents higher basal oxygen consumption than white adipose tissue and a positive response to b‐adrenergic stimulation. Considering the whole tissue and not just subcellular populations is a direct approach that provides a realistic view of physiological respiration. In addition, it can be adapted to analyze the effect of potential activators of thermogenesis, or to assess the use of fatty acids or glucose as a source of energy. PMID:28435771

Effect of Gender on the Total Abdominal Fat, Intra-Abdominal Adipose Tissue and Abdominal Sub-Cutaneous Adipose Tissue among Indian Hypertensive Patients.

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Sahoo, Jaya Prakash; Kumari, Savita; Jain, Sanjay

2016-04-01

Abdominal obesity is a better marker of adverse metabolic profile than generalized obesity in hypertensive subjects. Further, gender has effect on adiposity and its distribution. Effect of gender on obesity and the distribution of fat in different sub-compartments of abdomen among Indian hypertensive subjects. This observational study included 278 adult subjects (Males-149 & Females-129) with essential hypertension from a tertiary care centre in north India over one year. A detailed history taking and physical examination including anthropometry were performed in all patients. Total Abdominal Fat (TAF) and abdominal adipose tissue sub-compartments like Intra-Abdominal Adipose Tissue (IAAT) and Sub-Cutaneous Adipose Tissue (SCAT) were measured using the predictive equations developed for Asian Indians. Female hypertensive subjects had higher Body Mass Index (BMI) with more overweight (BMI ≥ 23kg/m(2)), and obesity (BMI≥ 25 kg/m(2)). Additionally, they had higher prevalence of central obesity based on both Waist Circumference (WC) criteria (WC≥ 90 cm in males and WC≥ 80 cm in females) and TAF criteria {≥245.6 cm(2) (males) and ≥203.46 cm(2) (females)} than male patients. But there was no difference in the prevalence of central obesity based on Waist Hip Ratio (WHR) criteria (WHR ≥0.90 in males and WHR ≥ 0.85 in females) between two genders. High TAF & IAAT were present in more females although there was no difference in the distribution of high SCAT between two genders. Female hypertensive subjects were more obese with higher abnormal TAF & IAAT compared to male patients. However, there was no difference in the distribution of high SCAT among them.

Differential effects of diet composition and timing of feeding behavior on rat brown adipose tissue and skeletal muscle peripheral clocks

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Paul de Goede

2018-01-01

Full Text Available The effects of feeding behavior and diet composition, as well as their possible interactions, on daily (clock gene expression rhythms have mainly been studied in the liver, and to a lesser degree in white adipose tissue (WAT, but hardly in other metabolic tissues such as skeletal muscle (SM and brown adipose tissues (BAT. We therefore subjected male Wistar rats to a regular chow or free choice high-fat-high sugar (fcHFHS diet in combination with time restricted feeding (TRF to either the light or dark phase. In SM, all tested clock genes lost their rhythmic expression in the chow light fed group. In the fcHFHS light fed group rhythmic expression for some, but not all, clock genes was maintained, but shifted by several hours. In BAT the daily rhythmicity of clock genes was maintained for the light fed groups, but expression patterns were shifted as compared with ad libitum and dark fed groups, whilst the fcHFHS diet made the rhythmicity of clock genes become more pronounced. Most of the metabolic genes in BAT tissue tested did not show any rhythmic expression in either the chow or fcHFHS groups. In SM Pdk4 and Ucp3 were phase-shifted, but remained rhythmically expressed in the chow light fed groups. Rhythmic expression was lost for Ucp3 whilst on the fcHFHS diet during the light phase. In summary, both feeding at the wrong time of day and diet composition disturb the peripheral clocks in SM and BAT, but to different degrees and thereby result in a further desynchronization between metabolically active tissues such as SM, BAT, WAT and liver.

Functionally enhanced brown adipose tissue in Ames dwarf mice.

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Darcy, Justin; Bartke, Andrzej

2017-01-02

Reduced insulin-like growth factor 1/insulin signaling (IIS) has been linked to extended longevity in species ranging from yeast to mammals. In mammals, this is exemplified in Ames dwarf (Prop1 df/df ) mice, which have a 40%-60% increase in longevity (males and females, respectively) due to their recessive Prop1 loss-of-function mutation that results in lack of growth hormone (GH), thyroid-stimulating hormone and prolactin. Our laboratory has previously shown that Ames dwarf mice have functionally unique white adipose tissue (WAT) that improves, rather than impairs, insulin sensitivity. Because GH and thyroid hormone are integral to adipose tissue development and function, we hypothesized that brown adipose tissue (BAT) in Ames dwarf mice may also be functionally unique and/or enhanced. Here, we elaborate on our recent findings, which demonstrate that BAT is functionally enhanced in Ames dwarf mice, and suggest that BAT removal in these mice results in utilization of WAT depots as an energy source. We also discuss how our findings compare to those in other long-lived dwarf mice with altered IIS, which unlike Ames dwarf mice, are essentially euthyroid. Lastly, we provide some insights into the implications of these findings and discuss some of the necessary future work in this area.

Activities of asymmetric dimethylarginine-related enzymes in white adipose tissue are associated with circulating lipid biomarkers

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Iwasaki Hiroaki

2012-04-01

Full Text Available Abstract Background Asymmetric NG,NG-dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase, is regulated by the enzymatic participants of synthetic and metabolic processes, i.e., type I protein N-arginine methyltransferase (PRMT and dimethylarginine dimethylaminohydrolase (DDAH. Previous reports have demonstrated that circulating ADMA levels can vary in patients with type 1 and type 2 diabetes mellitus (T2DM. White adipose tissue expresses the full enzymatic machinery necessary for ADMA production and metabolism; however, modulation of the activities of adipose ADMA-related enzymes in T2DM remains to be determined. Methods A rodent model of T2DM using 11- and 20-week old Goto-Kakizaki (GK rats was used. The expression and catalytic activity of PRMT1 and DDAH1 and 2 in the white adipose tissues (periepididymal, visceral and subcutaneous fats and femur skeletal muscle tissue were determined by immunoblotting, in vitro methyltransferase and in vitro citrulline assays. Results Non-obese diabetic GK rats showed low expression and activity of adipose PRMT1 compared to age-matched Wistar controls. Adipose tissues from the periepididymal, visceral and subcutaneous fats of GK rats had high DDAH1 expression and total DDAH activity, whereas the DDAH2 expression was lowered below the control value. This dynamic of ADMA-related enzymes in white adipose tissues was distinct from that of skeletal muscle tissue. GK rats had lower levels of serum non-esterified fatty acids (NEFA and triglycerides (TG than the control rats. In all subjects the adipose PRMT1 and DDAH activities were statistically correlated with the levels of serum NEFA and TG. Conclusion Activities of PRMT1 and DDAH in white adipose tissues were altered in diabetic GK rats in an organ-specific manner, which was reflected in the serum levels of NEFA and TG. Changes in adipose ADMA-related enzymes might play a part in the function of white adipose tissue.

Potential of Osteoblastic Cells Derived from Bone Marrow and Adipose Tissue Associated with a Polymer/Ceramic Composite to Repair Bone Tissue.

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Freitas, Gileade P; Lopes, Helena B; Almeida, Adriana L G; Abuna, Rodrigo P F; Gimenes, Rossano; Souza, Lucas E B; Covas, Dimas T; Beloti, Marcio M; Rosa, Adalberto L

2017-09-01

One of the tissue engineering strategies to promote bone regeneration is the association of cells and biomaterials. In this context, the aim of this study was to evaluate if cell source, either from bone marrow or adipose tissue, affects bone repair induced by osteoblastic cells associated with a membrane of poly(vinylidene-trifluoroethylene)/barium titanate (PVDF-TrFE/BT). Mesenchymal stem cells (MSC) were isolated from rat bone marrow and adipose tissue and characterized by detection of several surface markers. Also, both cell populations were cultured under osteogenic conditions and it was observed that MSC from bone marrow were more osteogenic than MSC from adipose tissue. The bone repair was evaluated in rat calvarial defects implanted with PVDF-TrFE/BT membrane and locally injected with (1) osteoblastic cells differentiated from MSC from bone marrow, (2) osteoblastic cells differentiated from MSC from adipose tissue or (3) phosphate-buffered saline. Luciferase-expressing osteoblastic cells derived from bone marrow and adipose tissue were detected in bone defects after cell injection during 25 days without difference in luciferin signal between cells from both sources. Corroborating the in vitro findings, osteoblastic cells from bone marrow combined with the PVDF-TrFE/BT membrane increased the bone formation, whereas osteoblastic cells from adipose tissue did not enhance the bone repair induced by the membrane itself. Based on these findings, it is possible to conclude that, by combining a membrane with cells in this rat model, cell source matters and that bone marrow could be a more suitable source of cells for therapies to engineer bone.

Human skeletal muscles replaced to a high degree by white adipose tissue.

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Ina, Keisuke; Kitamura, Hirokazu; Masaki, Takayuki; Tatsukawa, Shuji; Yoshimatsu, Hironobu; Fujikura, Yoshihisa

2011-02-01

Extreme replacement of skeletal muscles by adipose tissue was found in an 86-year old Japanese male cadaver during dissection practice for medical students at Oita University School of Medicine. Especially, the bilateral sartorius muscles looked overall like adipose tissue. The man had suffered from diabetes mellitus, renal failure, hypertension and hypothyroidism before his death. He was also an alcohol drinker. He had been bedridden late in life. The cause of death was renal failure. In microscopy, the adipose tissue-like sartorius muscle was shown to consist of leptin-positive adipocytes with a small number of degenerated muscle fibers. Fatty replacement, or fatty degeneration, appears to result from endocrine and metabolic disorders, and being bedridden leads to muscle atrophy and damage, although the origin of the adipocytes which emerged in the degenerated muscles is unknown.

mRNA Expression of Ovine Angiopoietin-like Protein 4 Gene in Adipose Tissues

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Jing Zhang

2016-05-01

Full Text Available Angiopoietin-like protein 4 (ANGPTL4 is involved in a variety of functions, including lipoprotein metabolism and angiogenesis. To reveal the role of ANGPTL4 in fat metabolism of sheep, ovine ANGPTL4 mRNA expression was analyzed in seven adipose tissues from two breeds with distinct tail types. Forty-eight animals with the gender ratio of 1:1 for both Guangling Large Tailed (GLT and Small Tailed Han (STH sheep were slaughtered at 2, 4, 6, 8, 10, and 12 months of age, respectively. Adipose tissues were collected from greater and lesser omental, subcutaneous, retroperitoneal, perirenal, mesenteric, and tail fats. Ontogenetic mRNA expression of ANGPTL4 in these adipose tissues from GTL and STH was studied by quantitative real time polymerase chain reaction. The results showed that ANGPTL4 mRNA expressed in all adipose tissues studied with the highest in subcutaneous and the lowest in mesenteric fat depots. Months of age, tissue and breed are the main factors that significantly influence the mRNA expression. These results provide new insights into ovine ANGPTL4 gene expression and clues for its function mechanism.

Brown adipose tissue (BAT specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation

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Juliane Weiner

2017-06-01

Full Text Available Objective: Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT biology. Methods: We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT and plasma levels. Vaspin expression was analyzed in isolated white and brown adipocytes during adipogenesis and in response to adrenergic stimuli. DNA-methylation within the vaspin promoter was analyzed to investigate acute epigenetic changes after cold-exposure in BAT. Results: Our results demonstrate a strong induction of vaspin mRNA and protein expression specifically in BAT of both cold-exposed and high-fat (HF or high-sugar (HS fed mice. While obesogenic diets also upregulated hepatic vaspin mRNA levels, cold exposure tended to increase vaspin gene expression of inguinal white adipose tissue (iWAT depots. Concomitantly, vaspin plasma levels were decreased upon obesogenic or thermogenic triggers. Vaspin expression was increased during adipogenesis but unaffected by sympathetic activation in brown adipocytes. Analysis of vaspin promoter methylation in AT revealed lowest methylation levels in BAT, which were acutely reduced after cold exposure. Conclusions: Our data demonstrate a novel BAT-specific regulation of vaspin gene expression upon physiological stimuli in vivo with acute epigenetic changes that may contribute to cold-induced expression in BAT. We conclude that these findings indicate functional relevance and potentially beneficial effects of vaspin in BAT function. Keywords: Brown adipose tissue, Browning, Cold exposure, DNA methylation, High-fat diet, High-sucrose diet, SerpinA12, Thermogenesis

Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice.