Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity.

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Arai, Takeshi; Kim, Hyoun-ju; Hirako, Satoshi; Nakasatomi, Maki; Chiba, Hiroshige; Matsumoto, Akiyo

2013-01-01

We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice. Copyright © 2013 Elsevier Inc. All rights reserved.

Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice.

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Buckman, Laura B; Thompson, Misty M; Lippert, Rachel N; Blackwell, Timothy S; Yull, Fiona E; Ellacott, Kate L J

2015-01-01

Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of these cells in the homeostatic response to the diet. The objective of this study was to determine physiologic role of astrocytes in the acute homeostatic response to high-fat feeding. We bred a transgenic mouse model with doxycycline-inducible inhibition of NFkappaB (NFκB) signaling in astrocytes to determine the effect of loss of NFκB-mediated astrocyte activation on acute high-fat hyperphagia. ELISA was used to measure the levels of markers of astrocyte activation, glial-fibrillary acidic protein (GFAP) and S100B, in the medial basal hypothalamus. Inhibition of NFκB signaling in astrocytes prevented acute high-fat diet-induced astrocyte activation and resulted in a 15% increase in caloric intake (P fat feeding.

Green tea (-)-epigallocatechin-3-gallate counteracts daytime overeating induced by high-fat diet in mice.

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Li, Hongyu; Kek, Huiling Calvina; Lim, Joy; Gelling, Richard Wayne; Han, Weiping

2016-12-01

High-fat diet (HFD) induces overeating and obesity. Green tea (-)-epigallocatechin-3-gallate (EGCG) reduces HFD-induced body weight and body fat gain mainly through increased lipid metabolism and fat oxidation. However, little is known about its effect on HFD-induced alterations in feeding behavior. Three diet groups of wildtype C57B/6j male mice at 5 months old were fed on normal chow diet, 1 week of HFD (60% of energy) and 3 months of HFD (diet-induced obesity (DIO)) prior to EGCG supplement in respective diet. EGCG had no effect on feeding behavior in normal chow diet group. Increased daytime feeding induced by HFD was selectively corrected by EGCG treatment in HFD groups, including reversed food intake, feeding frequency and meal size in HFD + EGCG group, and reduced food intake and feeding frequency in DIO + EGCG group. Moreover, EGCG treatment altered diurnally oscillating expression pattern of key appetite-regulating genes, including AGRP, POMC, and CART, and key circadian genes Clock and Bmal1 in hypothalamus of DIO mice, indicating its central effect on feeding regulation. Our study demonstrates that EGCG supplement specifically counteracts daytime overeating induced by HFD in mice, suggesting its central role in regulating feeding behavior and energy homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats.

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Panchal, Sunil K; Ward, Leigh; Brown, Lindsay

2013-03-01

Fruits and nuts may prevent or reverse common human health conditions such as obesity, diabetes and hypertension; together, these conditions are referred to as metabolic syndrome, an increasing problem. This study has investigated the responses to ellagic acid, present in many fruits and nuts, in a diet-induced rat model of metabolic syndrome. Eight- to nine-week-old male Wistar rats were divided into four groups for 16-week feeding with cornstarch diet (C), cornstarch diet supplemented with ellagic acid (CE), high-carbohydrate, high-fat diet (H) and high-carbohydrate, high-fat diet supplemented with ellagic acid (HE). CE and HE rats were given 0.8 g/kg ellagic acid in food from week 8 to 16 only. At the end of 16 weeks, cardiovascular, hepatic and metabolic parameters along with protein levels of Nrf2, NF-κB and CPT1 in the heart and the liver were characterised. High-carbohydrate, high-fat diet-fed rats developed cardiovascular remodelling, impaired ventricular function, impaired glucose tolerance, non-alcoholic fatty liver disease with increased protein levels of NF-κB and decreased protein levels of Nrf2 and CPT1 in the heart and the liver. Ellagic acid attenuated these diet-induced symptoms of metabolic syndrome with normalisation of protein levels of Nrf2, NF-κB and CPT1. Ellagic acid derived from nuts and fruits such as raspberries and pomegranates may provide a useful dietary supplement to decrease the characteristic changes in metabolism and in cardiac and hepatic structure and function induced by a high-carbohydrate, high-fat diet by suppressing oxidative stress and inflammation.

High fat diet feeding results in gender specific steatohepatitis and inflammasome activation.

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Ganz, Michal; Csak, Timea; Szabo, Gyongyi

2014-07-14

To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis (NASH), which has been a challenge. In this study, we used a high fat diet (HFD) feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States. We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively, and evaluated the extent of liver damage, steatosis, and inflammasome activation. Our methods included histopathological analysis to assess liver damage and steatosis, which involved H and E and oil-red-o staining; biochemical studies to look at ALT and triglyceride levels; RNA analysis using quantitative polymerase chain reaction; and cytokine analysis, which included the enzyme-linked immunosorbent assay method to look at interleukin (IL)-1β and tumor necrosis factor-α (TNFα) levels. Furthermore, at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests (ITT) and glucose tolerance tests. There was no insulin resistance, steatosis, or inflammasome activation at 6 wk. In contrast, at 16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male, but not female mice. In males, elevated alanine aminotransferase and triglyceride levels, indicated liver damage and steatosis, respectively. Increased liver TNFα and monocyte chemoattractant protein-1 mRNA and protein, correlated with steatohepatitis. The inflammasome components, adaptor molecule, Aim2, and NOD-like receptor 4, increased at the mRNA level, and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1β protein levels in male mice fed a long-term HFD. Male mice on HFD had increased α-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis. In contrast, female mice displayed only elevated triglyceride levels, steatosis, and no fibrosis. Our data

Effect of short-term low- and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects.

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Guay, Valérie; Lamarche, Benoît; Charest, Amélie; Tremblay, André J; Couture, Patrick

2012-01-01

High-fat, low-carbohydrate diets have been shown to raise plasma cholesterol levels, an effect associated with the formation of large low-density lipoprotein (LDL) particles. However, the impact of dietary intervention on time-course changes in LDL particle size has not been investigated. To test whether a short-term dietary intervention affects LDL particle size, we conducted a randomized, double-blind, crossover study using an intensive dietary modification in 12 nonobese healthy men with normal plasma lipid profile. Participants were subjected to 2 isocaloric 3-day diets: high-fat diet (37% energy from fat and 50% from carbohydrates) and low-fat diet (25% energy from fat and 62% from carbohydrates). Plasma lipid levels and LDL particle size were assessed on fasting blood samples after 3 days of feeding on each diet. The LDL particles were characterized by polyacrylamide gradient gel electrophoresis. Compared with the low-fat diet, plasma cholesterol, LDL cholesterol, and high-density lipoprotein cholesterol were significantly increased (4.45 vs 4.78 mmol/L, P = .04; 2.48 vs 2.90 mmol/L, P = .005; and 1.29 vs 1.41 mmol/L, P = .005, respectively) following the 3-day high-fat diet. Plasma triglycerides and fasting apolipoprotein B-48 levels were significantly decreased after the high-fat diet compared with the low-fat diet (1.48 vs 1.01 mmol/L, P = .0003 and 9.6 vs 5.5 mg/L, P = .008, respectively). The high-fat diet was also associated with a significant increase in LDL particle size (255.0 vs 255.9 Å;P = .01) and a significant decrease in the proportion of small LDL particle (vs 44.6%, P = .01). As compared with a low-fat diet, the cholesterol-raising effect of a high-fat diet is associated with the formation of large LDL particles after only 3 days of feeding. Copyright © 2012 Elsevier Inc. All rights reserved.

Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice

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Buckman, Laura B.; Thompson, Misty M.; Lippert, Rachel N.; Blackwell, Timothy S.; Yull, Fiona E.; Ellacott, Kate L.J.

2014-01-01

Objective Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of these cells in the homeostatic response to the diet. The objective of this study was to determine physiologic role of astrocytes in the acute homeostatic response to high-fat feeding. Methods We bred a transgenic mouse model with doxycycline-inducible inhibition of NFkappaB (NFκB) signaling in astrocytes to determine the effect of loss of NFκB-mediated astrocyte activation on acute high-fat hyperphagia. ELISA was used to measure the levels of markers of astrocyte activation, glial-fibrillary acidic protein (GFAP) and S100B, in the medial basal hypothalamus. Results Inhibition of NFκB signaling in astrocytes prevented acute high-fat diet-induced astrocyte activation and resulted in a 15% increase in caloric intake (P < 0.01) in the first 24 h after introduction of the diet. Conclusions These data reveal a novel homeostatic role for astrocytes in the acute physiologic regulation of food intake in response to high-fat feeding. PMID:25685690

High-fat feeding increases hepatic vitamin C synthesis and its circulatory mobilization in mice

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Christensen, Britt Tranberg; Hansen, Axel Jacob Kornerup; Lykkesfeldt, Jens

2014-01-01

, glucose and vitC concentrations. Hepatic vitC concentration and gulonolactone oxidase (GLO) capacity, as a measure of vitC de novo biosynthesis, were analyzed in liver homogenates. RESULTS: HF diet significantly increased plasma concentrations of vitC compared with a control diet low in fat (P ... to modulate their vitC homeostasis during high-fat (HF) feeding. METHODS: Twenty-five male 5-week-old C57BL/6 mice were fed high- or low-fat diets for 14 weeks. An oral glucose tolerance test (OGTT) was performed after 12 weeks of intervention. Terminal fasting plasma samples were analyzed for insulin.......05). Hepatic de novo biosynthesis of vitC was upregulated (P glucose and insulin concentrations...

Dietary D-psicose reduced visceral fat mass in high-fat diet-induced obese rats.

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Chung, Young-Mee; Hyun Lee, Joo; Youl Kim, Deuk; Hwang, Se-Hee; Hong, Young-Ho; Kim, Seong-Bo; Jin Lee, Song; Hye Park, Chi

2012-02-01

D-Psicose, a C-3 epimer of D-fructose, has shown promise in reducing body fat accumulation in normal rats and plasma glucose level in genetic diabetic mice. Effects of D-psicose on diet-induced obesity are not clearly elucidated, and we investigated food intake, body weight, and fat accumulation in rats fed high-fat (HF) diet. Sprague-Dawley rats became obese by feeding HF diet for 4 wk, and were assigned either to normal or HF diet supplemented with or without D-psicose, sucrose, or erythritol for 8 wk. Changing HF to normal diet gained less body weight and adipose tissue due to different energy intake. D-psicose-fed rats exhibited lower weight gain, food efficiency ratio, and fat accumulation than erythritol- and sucrose-fed rats. This effect was more prominent in D-psicose-fed rats with normal diet than with HF diet, suggesting combination of psicose and calorie restriction further reduced obesity. There was no difference in serum cholesterol/high-density lipoprotein (HDL)-C and low-density lipoprotein (LDL)-C/HDL-C ratios between D-psicose group and other groups. Liver weight in 5% psicose group with normal diet was higher than in other groups, but histopathological examination did not reveal any psicose-related change. D-Psicose inhibited the differentiation of mesenchymal stem cell (MSC) to adipose tissue in a concentration-dependent manner. These results demonstrate that D-psicose produces a marked decrease, greater than erythritol, in weight gain and visceral fat in an established obesity model by inhibiting MSC differentiation to adipocyte. Thus, D-psicose can be useful in preventing and reducing obesity as a sugar substitute and food ingredient. We can develop D-psicose as a sugar substitute and food ingredient since it can prevent obesity in normal people, but also suppress adiposity as a sugar substitute or food ingredients with antiobesity effect in obese people. D-psicose can be unique functional sweetener because of its function of reducing visceral

Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.

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Mercer, Kelly E; Pulliam, Casey F; Pedersen, Kim B; Hennings, Leah; Ronis, Martin Jj

2017-03-01

Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein

High-fat diet feeding differentially affects the development of inflammation in the central nervous system.

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Guillemot-Legris, Owein; Masquelier, Julien; Everard, Amandine; Cani, Patrice D; Alhouayek, Mireille; Muccioli, Giulio G

2016-08-26

Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone. We used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16 weeks) a group of mice fed a high-fat diet with its respective control group fed a standard diet. We also performed a large-scale analysis of lipids in the central nervous system using HPLC-MS, and we then tested the lipids of interest on a primary co-culture of astrocytes and microglial cells. We measured an increase in the inflammatory tone in the cerebellum at the different time-points. However, at week 16, we evidenced that the inflammatory tone displayed significant differences in two different regions of the central nervous system, specifically an increase in the cerebellum and no modification in the cortex for high-fat diet mice when compared with chow-fed mice. Our results clearly suggest region-dependent as well as time-dependent adaptations of the central nervous system to the high-fat diet. The differences in inflammatory tone between the two regions considered seem to involve astrocytes but not microglial cells. Furthermore, a large-scale lipid screening coupled to ex vivo testing enabled us to identify three classes of lipids-phosphatidylinositols, phosphatidylethanolamines, and lysophosphatidylcholines-as well as palmitoylethanolamide, as potentially responsible for the difference in inflammatory tone. This study demonstrates that the inflammatory tone induced by a high-fat diet does not similarly affect distinct regions of the central nervous system. Moreover, the lipids identified and tested ex vivo showed interesting anti-inflammatory properties and could be further studied to better characterize

IGF-1 Alleviates High Fat Diet-Induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function

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Zhang, Yingmei; Yuan, Ming; Bradley, Katherine M.; Dong, Feng; Anversa, Piero; Ren, Jun

2012-01-01

Obesity is often associated with reduced plasma IGF-1 levels, oxidative stress, mitochondrial damage and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high fat diet-induced oxidative, myocardial, geometric and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low (10%) or high fat (45%) diet to induce obesity. High fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin-6, insulin and triglyceride as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end systolic and diastolic diameter, increased wall thickness, and cardiac hypertrophy in high fat-fed FVB mice. High fat diet promoted ROS generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca2+ dysregulation, including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, and dampened intracellular Ca2+ rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor, post-receptor signaling molecules IRS-1 (tyrosine/serine phosphorylation), Akt, GSK3β, Foxo3a, mTOR, as well as downregulated expression of mitochondrial proteins PPARγ coactivator 1α (PGC1α) and UCP-2. Intriguingly, IGF-1 mitigated high fat diet feeding-induced alterations in ROS, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca2+ handling and insulin signaling, but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly due to preserved cell survival, mitochondrial function and insulin signaling. PMID:22275536

Effect of feeding a high-fat diet independently of caloric intake on reproductive function in diet-induced obese female rats

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Hussain, Mona A.; Abogresha, Noha M.; Tamany, Dalia A.; Lotfy, Mariam

2016-01-01

Introduction Globally, the prevalence of overweight and obesity is increasing, predisposing females to health hazards including compromised reproductive capacity. Our objective was to investigate the effect of ad libitum, isocalorically and hypocalorically restricted high-fat diet (HFD) feeding on reproductive function in diet-induced obese female rats. Material and methods Twenty female albino Sprague Dawley rats were used; 5 rats were kept on a standard pellet animal diet to serve as a control group (A) and 15 rats were fed a HFD for 9 weeks to induce obesity. The HFD fed animals were equally divided into three groups: an ad libitum HFD group (B), an isocalorically restricted HFD group (C), and a hypocalorically restricted HFD group (D). Estrous cyclicity, hormonal levels, ovarian histopathology and caspase-3 immunoreactivity were evaluated. Results The HFD-fed rats in groups B, C and D had significant irregularity in estrous cyclicity Vs group A (p = 0.001, 0.003 and 0.034 respectively). Groups C and D had significant reduction in serum progesterone level (p = 0.006 and 0.018 Vs A). Isocaloric restriction of HFD feeding significantly increased serum LH. Groups B and C had a significant increase in caspase-3 expression in the ovary (p < 0.001). Conclusions Ad libitum HFD interfered with the normal estrous cycle and enhanced apoptosis of luteal cells in obese female rats. The HFD restriction interfered with the normal estrous cycle and caused functional insufficiency of the corpus luteum in obese female rats. These results suggest that HFD feeding determinately affects female reproductive function independently of caloric intake. PMID:27478474

The effects of high-fat diets composed of different animal and vegetable fat sources on the health status and tissue lipid profiles of male Japanese quail (

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Janine Donaldson

2017-05-01

Full Text Available Objective The current study aimed to investigate the impact of high-fat diets composed of different animal and vegetable fat sources on serum metabolic health markers in Japanese quail, as well as the overall lipid content and fatty acid profiles of the edible bird tissues following significantly increased dietary lipid supplementation. Methods Fifty seven male quail were divided into six groups and fed either a standard diet or a diet enriched with one of five different fats (22% coconut oil, lard, palm oil, soybean oil, or sunflower oil for 12 weeks. The birds were subjected to an oral glucose tolerance test following the feeding period, after which they were euthanized and blood, liver, breast, and thigh muscle samples collected. Total fat content and fatty acid profiles of the tissue samples, as well as serum uric acid, triglyceride, cholesterol, total protein, albumin, aspartate transaminase, and total bilirubin concentrations were assessed. Results High-fat diet feeding had no significant effects on the glucose tolerance of the birds. Dietary fatty acid profiles of the added fats were reflected in the lipid profiles of both the liver and breast and thigh muscle tissues, indicating successful transfer of dietary fatty acids to the edible bird tissues. The significantly increased level of lipid inclusion in the diets of the quail used in the present study was unsuccessful in increasing the overall lipid content of the edible bird tissues. Serum metabolic health markers in birds on the high-fat diets were not significantly different from those observed in birds on the standard diet. Conclusion Thus, despite the various high-fat diets modifying the fatty acid profile of the birds’ tissues, unlike in most mammals, the birds maintained a normal health status following consumption of the various high-fat diets.

A Free-Choice High-Fat High-Sugar Diet Alters Day-Night Per2 Gene Expression in Reward-Related Brain Areas in Rats.

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Blancas-Velazquez, Aurea Susana; Unmehopa, Unga A; Eggels, Leslie; Koekkoek, Laura; Kalsbeek, Andries; Mendoza, Jorge; la Fleur, Susanne E

2018-01-01

Under normal light-dark conditions, nocturnal rodents consume most of their food during the dark period. Diets high in fat and sugar, however, may affect the day-night feeding rhythm resulting in a higher light phase intake. In vitro and in vivo studies showed that nutrients affect clock-gene expression. We therefore hypothesized that overconsuming fat and sugar alters clock-gene expression in brain structures important for feeding behavior. We determined the effects of a free-choice high-fat high-sugar (fcHFHS) diet on clock-gene expression in rat brain areas related to feeding and reward and compared them with chow-fed rats. Consuming a fcHFHS diet for 6 weeks disrupted day-night differences in Per2 mRNA expression in the nucleus accumbens (NAc) and lateral hypothalamus but not in the suprachiasmatic nucleus, habenula, and ventral tegmental area. Furthermore, short-term sugar drinking, but not fat feeding, upregulates Per2 mRNA expression in the NAc. The disruptions in day-night differences in NAc Per2 gene expression were not accompanied by altered day-night differences in the mRNA expression of peptides related to food intake. We conclude that the fcHFHS diet and acute sugar drinking affect Per2 gene expression in areas involved in food reward; however, this is not sufficient to alter the day-night pattern of food intake.

Modulatory effects of dietary supplementation by Vernonia amygdalina on high-fat-diet-induced obesity in Wistar rats.

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Ekeleme-Egedigwe, Chima A; Ijeh, Ifeoma I; Okafor, Polycarp N

2017-01-01

Obesity is a growing public health problem arising from energy imbalance. The effect of 10% dietary incorporation of Vernonia amygdalina (VA) leaves into high-fat diets on some biological markers of adiposity and dyslipidaemia was investigated. Experimental diets consisted of the following – CD (control diet); HFD (high-fat diet); and HFD- VA (HFD containing 10% Vernonia amygdalina leaves) supplementation. Fifteen male Wistar rats were randomly divided into three groups of five animals each. After twelve weeks of feeding, serum lipid profile, blood glucose concentrations, body weight, adiposity index, feed intake, fecal loss and relative organ weight were investigated. Vernonia amygdalina (VA) inhibited HFD-induced weight gain and adiposity in rats. HFD-induced obese rats showed a significant increase in the levels of serum TG and TC compared to rats on a normal diet. However, the levels of serum TG, TC, LDL-C in HFDVA rats reduced significantly relative to the levels in HFD rats. Our results indicate that HFDVA reversed fatty infiltration leading to decreased body weight and fat tissue mass in the rats. These results suggested that incorporation of Vernonia amygdalina into high-fat diets may have therapeutic potentials for obesity and related metabolic disorders. Further studies to explore its possibility as an alternative pharmacologic agent to treat obesity are warranted.

Effects of high fat diet on the Basal activity of the hypothalamus-pituitary-adrenal axis in mice: a systematic review.

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Auvinen, H E; Romijn, J A; Biermasz, N R; Havekes, L M; Smit, J W A; Rensen, P C N; Pereira, A M

2011-12-01

Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the hypothalamus-pituitary-adrenal-axis activation. The aim of this review was to assess the effects of high fat feeding on the activity of the hypothalamus-pituitary-adrenal-axis in mice. PubMed, EMBASE, Web of Science, the Cochrane database, and Science Direct were electronically searched and reviewed by 2 individual researchers. We included only original mouse studies reporting parameters of the hypothalamus-pituitary-adrenal-axis after high fat feeding, and at least 1 basal corticosterone level with a proper control group. Studies with adrenalectomized mice, transgenic animals only, high fat diet for less than 2 weeks, or other interventions besides high fat diet, were excluded. 20 studies were included. The hypothalamus-pituitary-adrenal-axis evaluation was the primary research question in only 5 studies. Plasma corticosterone levels were unchanged in 40%, elevated in 30%, and decreased in 20% of the studies. The effects in the peripheral tissues and the central nervous system were also inconsistent. However, major differences were found between mouse strains, experimental conditions, and the content and duration of the diets. This systematic review demonstrates that the effects of high fat feeding on the basal activity of the hypothalamus-pituitary-adrenal-axis in mice are limited and inconclusive. Differences in experimental conditions hamper comparisons and accentuate the need for standardized evaluations to discern the effects of diet-induced obesity on the hypothalamus-pituitary-adrenal-axis. © Georg Thieme Verlag KG Stuttgart · New York.

Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet.

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Dubinion, John H; da Silva, Alexandre A; Hall, John E

2011-04-01

Obesity has been suggested to induce selective leptin resistance whereby leptin's anorexic effects are attenuated, whereas the effects to increase sympathetic nervous system activity and blood pressure remain intact. Most studies, however, have tested only the acute responses to leptin administration. This study tested whether feeding a high-fat diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion. Sprague-Dawley rats were fed high-fat diet (40% kcal from fat, n=5) or normal-fat diet (13% kcal from fat, n=5) for a year. Radiotelemeters were implanted for continuous monitoring of mean arterial pressure (MAP) and heart rate (HR). A 21G steel cannula was implanted in the lateral cerebral ventricle [intracerebroventricular (ICV)]. After recovery, leptin was infused ICV at 0.02 μg/kg per min for 10 days. High-fat rats were heavier than normal-fat rats (582±12 vs. 511±19 g) and exhibited significantly higher MAP (114±3 vs. 96±7 mmHg). Although the acute (24 h) effects of leptin were attenuated in high-fat rats, chronic ICV leptin infusion decreased caloric intake in both groups similarly (50±8 vs. 40±10%) by day 5. Despite decreased food intake and weight loss, leptin infusion significantly increased MAP and HR in both high-fat and normal-fat rats (7±2 and 5±1 mmHg; 18±11 and 21±10 b.p.m., respectively). These results suggest that obesity induced by feeding a high-fat diet blunts the acute anorexic effects of leptin but does not cause significant resistance to the chronic central nervous system effects of leptin on appetite, MAP, or HR.

Consequences of exchanging carbohydrates for proteins in the cholesterol metabolism of mice fed a high-fat diet.

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Frédéric Raymond

Full Text Available Consumption of low-carbohydrate, high-protein, high-fat diets lead to rapid weight loss but the cardioprotective effects of these diets have been questioned. We examined the impact of high-protein and high-fat diets on cholesterol metabolism by comparing the plasma cholesterol and the expression of cholesterol biosynthesis genes in the liver of mice fed a high-fat (HF diet that has a high (H or a low (L protein-to-carbohydrate (P/C ratio. H-P/C-HF feeding, compared with L-P/C-HF feeding, decreased plasma total cholesterol and increased HDL cholesterol concentrations at 4-wk. Interestingly, the expression of genes involved in hepatic steroid biosynthesis responded to an increased dietary P/C ratio by first down-regulation (2-d followed by later up-regulation at 4-wk, and the temporal gene expression patterns were connected to the putative activity of SREBF1 and 2. In contrast, Cyp7a1, the gene responsible for the conversion of cholesterol to bile acids, was consistently up-regulated in the H-P/C-HF liver regardless of feeding duration. Over expression of Cyp7a1 after 2-d and 4-wk H-P/C-HF feeding was connected to two unique sets of transcription regulators. At both time points, up-regulation of the Cyp7a1 gene could be explained by enhanced activations and reduced suppressions of multiple transcription regulators. In conclusion, we demonstrated that the hypocholesterolemic effect of H-P/C-HF feeding coincided with orchestrated changes of gene expressions in lipid metabolic pathways in the liver of mice. Based on these results, we hypothesize that the cholesterol lowering effect of high-protein feeding is associated with enhanced bile acid production but clinical validation is warranted. (246 words.

Consequences of exchanging carbohydrates for proteins in the cholesterol metabolism of mice fed a high-fat diet.

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Raymond, Frédéric; Wang, Long; Moser, Mireille; Metairon, Sylviane; Mansourian, Robert; Zwahlen, Marie-Camille; Kussmann, Martin; Fuerholz, Andreas; Macé, Katherine; Chou, Chieh Jason

2012-01-01

Consumption of low-carbohydrate, high-protein, high-fat diets lead to rapid weight loss but the cardioprotective effects of these diets have been questioned. We examined the impact of high-protein and high-fat diets on cholesterol metabolism by comparing the plasma cholesterol and the expression of cholesterol biosynthesis genes in the liver of mice fed a high-fat (HF) diet that has a high (H) or a low (L) protein-to-carbohydrate (P/C) ratio. H-P/C-HF feeding, compared with L-P/C-HF feeding, decreased plasma total cholesterol and increased HDL cholesterol concentrations at 4-wk. Interestingly, the expression of genes involved in hepatic steroid biosynthesis responded to an increased dietary P/C ratio by first down-regulation (2-d) followed by later up-regulation at 4-wk, and the temporal gene expression patterns were connected to the putative activity of SREBF1 and 2. In contrast, Cyp7a1, the gene responsible for the conversion of cholesterol to bile acids, was consistently up-regulated in the H-P/C-HF liver regardless of feeding duration. Over expression of Cyp7a1 after 2-d and 4-wk H-P/C-HF feeding was connected to two unique sets of transcription regulators. At both time points, up-regulation of the Cyp7a1 gene could be explained by enhanced activations and reduced suppressions of multiple transcription regulators. In conclusion, we demonstrated that the hypocholesterolemic effect of H-P/C-HF feeding coincided with orchestrated changes of gene expressions in lipid metabolic pathways in the liver of mice. Based on these results, we hypothesize that the cholesterol lowering effect of high-protein feeding is associated with enhanced bile acid production but clinical validation is warranted. (246 words).

A low-fat high-carbohydrate diet reduces plasma total adiponectin concentrations compared to a moderate-fat diet with no impact on biomarkers of systemic inflammation in a randomized controlled feeding study.

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Song, Xiaoling; Kestin, Mark; Schwarz, Yvonne; Yang, Pamela; Hu, Xiaojun; Lampe, Johanna W; Kratz, Mario

2016-02-01

We compared the effects of a eucaloric moderate-fat diet (18% protein, 36% fat, and 46% carbohydrate), a eucaloric low-fat high-carbohydrate diet (18% protein, 18% fat, and 64% carbohydrate), and a low-calorie (33% reduced) low-fat high-carbohydrate diet on biomarkers of systemic inflammation. We randomly assigned 102 participants (age 21-76 years and BMI 19.2-35.5 kg/m(2)) to the three different diets for 6 weeks in a parallel design intervention trial. All foods were provided. Ninety-three participants completed all study procedures; 92 were included in the analyses. Endpoints included plasma C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptors I and II (sTNFRI and II), and adiponectin. In the unadjusted primary analyses, none of the endpoints were differentially affected by the dietary interventions despite the significantly greater reductions in body weight and fat mass in participants consuming the low-calorie low-fat diet compared to the eucaloric diets (p loss (time × weight change interaction, p = 0.051). Adjusted for weight change, adiponectin was reduced in the groups consuming the low-fat diets relative to the moderate-fat diet (p = 0.008). No effect of the intervention diets or weight loss on CRP, IL-6, or sTNFRI and II was seen in these secondary analyses. In relatively healthy adults, moderate weight loss had minimal effects on systemic inflammation, and raised plasma adiponectin only modestly. A lower dietary fat and higher carbohydrate content had little impact on measures of systemic inflammation, but reduced adiponectin concentrations compared to a moderate-fat diet. The latter may be of concern given the consistent and strong inverse association of plasma adiponectin with many chronic diseases.

Andrographis paniculata extract attenuates pathological cardiac hypertrophy and apoptosis in high-fat diet fed mice.

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Hsieh, You-Liang; Shibu, Marthandam Asokan; Lii, Chong-Kuei; Viswanadha, Vijaya Padma; Lin, Yi-Lin; Lai, Chao-Hung; Chen, Yu-Feng; Lin, Kuan-Ho; Kuo, Wei-Wen; Huang, Chih-Yang

2016-11-04

Andrographis paniculata (Burm. f.) Nees (Acanthaceae) has a considerable medicinal reputation in most parts of Asia as a potent medicine in the treatment of Endocrine disorders, inflammation and hypertension. Water extract of A. paniculata and its active constituent andrographolide are known to possess anti-inflammatory and anti-apoptotic effects. Our aim is to identify whether A. paniculata extract could protect myocardial damage in high-fat diet induced obese mice. The test mice were divided into three groups fed either with normal chow or with high fat diet (obese) or with high fat diet treated with A. paniculata extract (2g/kg/day, through gavage, for a week). We found that the myocardial inflammation pathway related proteins were increased in the obese mouse which potentially contributes to cardiac hypertrophy and myocardial apoptosis. But feeding with A. paniculata extract showed significant inhibition on the effects of high fat diet. Our study strongly suggests that supplementation of A. paniculata extract can be used for prevention and treatment of cardiovascular disease in obese patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cardamom powder supplementation prevents obesity, improves glucose intolerance, inflammation and oxidative stress in liver of high carbohydrate high fat diet induced obese rats.

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Rahman, Md Mizanur; Alam, Mohammad Nazmul; Ulla, Anayt; Sumi, Farzana Akther; Subhan, Nusrat; Khan, Trisha; Sikder, Bishwajit; Hossain, Hemayet; Reza, Hasan Mahmud; Alam, Md Ashraful

2017-08-14

Cardamom is a well-known spice in Indian subcontinent, used in culinary and traditional medicine practices since ancient times. The current investigation was untaken to evaluate the potential benefit of cardamom powder supplementation in high carbohydrate high fat (HCHF) diet induced obese rats. Male Wistar rats (28 rats) were divided into four different groups such as Control, Control + cardamom, HCHF, HCHF + cardamom. High carbohydrate and high fat (HCHF) diet was prepared in our laboratory. Oral glucose tolerance test, organs wet weight measurements and oxidative stress parameters analysis as well as liver marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities were assayed on the tissues collected from the rats. Plasma lipids profiles were also measured in all groups of animals. Moreover, histological staining was also performed to evaluate inflammatory cells infiltration and fibrosis in liver. The current investigation showed that, HCHF diet feeding in rats developed glucose intolerance and increased peritoneal fat deposition compared to control rats. Cardamom powder supplementation improved the glucose intolerance significantly (p > 0.05) and prevented the abdominal fat deposition in HCHF diet fed rats. HCHF diet feeding in rats also developed dyslipidemia, increased fat deposition and inflammation in liver compared to control rats. Cardamom powder supplementation significantly prevented the rise of lipid parameters (p > 0.05) in HCHF diet fed rats. Histological assessments confirmed that HCHF diet increased the fat deposition and inflammatory cells infiltration in liver which was normalized by cardamom powder supplementation in HCHF diet fed rats. Furthermore, HCHF diet increased lipid peroxidation, decreased antioxidant enzymes activities and increased advanced protein oxidation product level significantly (p > 0.05) both in plasma and liver tissue which were modulated by

Increased Hypothalamic Inflammation Associated with the Susceptibility to Obesity in Rats Exposed to High-Fat Diet

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Xiaoke Wang

2012-01-01

Full Text Available Inflammation has been implicated in the hypothalamic leptin and insulin resistance resulting defective food intake during high fat diet period. To investigate hypothalamic inflammation in dietary induced obesity (DIO and obesity resistant (DIO-R rats, we established rat models of DIO and DIO-R by feeding high fat diet for 10 weeks. Then we switched half of DIO and DIO-R rats to chow food and the other half to high fat diet for the following 8 weeks to explore hypothalamic inflammation response to the low fat diet intervention. Body weight, caloric intake, HOMA-IR, as well as the mRNA expression of hypothalamic TLR4, NF-κB, TNF-α, IL-1β, and IL-6 in DIO/HF rats were significantly increased compared to DIO-R/HF and CF rats, whereas IL-10 mRNA expression was lower in both DIO/HF and DIO-R/HF rats compared with CF rats. Switching to chow food from high fat diet reduced the body weight and improved insulin sensitivity but not affecting the expressions of studied inflammatory genes in DIO rats. Take together, upregulated hypothalamic inflammation may contribute to the overeating and development of obesity susceptibility induced by high fat diet. Switching to chow food had limited role in correcting hypothalamic inflammation in DIO rats during the intervention period.

Liver protein expression in young pigs in response to a high-fat diet and diet restriction

DEFF Research Database (Denmark)

Sejersen, Henrik; Sørensen, Martin Tang; Larsen, Torben

2013-01-01

We investigated the liver response in young pigs to a high-fat diet (containing 25% animal fat) and diet restriction (equivalent to 60% of maintenance) using differential proteome analysis. The objective was to investigate whether young pigs can be used to model the liver response in adolescents...... to a high-fat diet and diet restriction-induced BW loss. The high-fat diet increased (P high-fat diet had normal glucose tolerance and liver lipid content despite a general increase (P ...-density lipoprotein decreased (P high-fat diet in young pigs is similar to that of humans in terms of increased fatty acid oxidation whereas the liver response to diet restriction is similar to humans...

Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change.

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Rinnankoski-Tuikka, Rita; Hulmi, Juha J; Torvinen, Sira; Silvennoinen, Mika; Lehti, Maarit; Kivelä, Riikka; Reunanen, Hilkka; Kujala, Urho M; Kainulainen, Heikki

2014-08-01

The relation between lipid accumulation and influence of exercise on insulin sensitivity is not straightforward. A proper balance between lipid droplet synthesis, lipolysis, and oxidative metabolism would ensure low local intramyocellular fatty acid levels, thereby possibly protecting against lipotoxicity-associated insulin resistance. This study investigated whether the accumulation of triglycerides and lipid droplets in response to high availability of fatty acids after high-fat feeding would parallel the abundance of intramyocellular perilipin proteins, especially PLIN5. The effects on these variables after diet change or voluntary running exercise intervention in skeletal muscle were also investigated. During a 19-week experiment, C57BL/6J mice were studied in six different groups: low-fat diet sedentary, low-fat diet active, high-fat diet sedentary, high-fat diet active and two groups which were high-fat sedentary for nine weeks, after which divided into low-fat sedentary or low-fat active groups. Myocellular triglyceride concentration and perilipin protein expression levels were assessed. We show that, concurrently with impaired insulin sensitivity, the expression level of PLIN5 and muscular triglyceride concentration increased dramatically after high-fat diet. These adaptations were reversible after the diet change intervention with no additional effect of exercise. After high-fat diet, lipid droplets become larger providing more surface area for PLIN5. We suggest that PLIN5 is an important regulator of lipid droplet turnover in altered conditions of fatty acid supply and consumption. Imbalances in lipid droplet metabolism and turnover might lead to lipotoxicity-related insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

Haloperidol and Rimonabant Increase Delay Discounting in Rats Fed High-Fat and Standard-Chow Diets

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Boomhower, Steven R.; Rasmussen, Erin B.

2016-01-01

The dopamine and endocannabinoid neurotransmitter systems have been implicated in delay discounting, a measure of impulsive choice, and obesity. The current study was designed to determine the extent to which haloperidol and rimonabant affected delay discounting in rats fed standard-chow and high-fat diets. Sprague-Dawley rats were allowed to free-feed under a high-fat diet (4.73 kcal/g) or a standard-chow diet (3.0 kcal/g) for three months. Then, operant sessions began in which rats (n = 9 standard chow; n = 10 high-fat) chose between one sucrose pellet delivered immediately vs. three sucrose pellets after a series of delays. In another condition, carrot-flavored pellets replaced sucrose pellets. After behavior stabilized, acute injections of rimonabant (0.3-10 mg/kg) and haloperidol (0.003-0.1 mg/kg) were administered i.p. before some choice sessions in both pellet conditions. Haloperidol and rimonabant increased discounting in both groups of rats by decreasing percent choice for the larger reinforcer and area-under-the-curve (AUC) values. Rats in the high-fat diet condition demonstrated increased sensitivity to haloperidol compared to chow-fed controls: haloperidol increased discounting in both dietary groups in the sucrose condition,, but only in the high-fat-fed rats in the carrot-pellet condition. These findings indicate that blocking D2 and CB1 receptors results in increased delay discounting, and that a high-fat diet may alter sensitivity to dopaminergic compounds using the delay-discounting task. PMID:25000488

High-fat diet induced insulin resistance in pregnant rats through pancreatic pax6 signaling pathway.

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Wu, Hao; Liu, Yunyun; Wang, Hongkun; Xu, Xianming

2015-01-01

To explore the changes in pancreas islet function of pregnant rats after consumption of high-fat diet and the underlying mechanism. Thirty pregnant Wistar rats were randomly divided into two groups: high-fat diet group and normal control group. Twenty days after gestation, fasting blood glucose concentration (FBG) and fasting serum insulin concentration (FINS) were measured. Then, oral glucose tolerance test (OGTT) and insulin release test (IRT) were performed. Finally, all the rats were sacrificed and pancreas were harvested. Insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were calculated according to FBG and FINS. RT-PCR and Real-time PCR were performed to study the expression of paired box 6 transcription factor (Pax6) and its target genes in pancreatic tissues. The body weight was significantly increased in the high-fat diet group compared with that of normal control rats (Pinsulin concentration between the two groups. OGTT and IRT were abnormal in the high-fat diet group. The high-fat diet rats were more prone to impaired glucose tolerance and insulin resistance. The level of the expression of Pax6 transcription factor and its target genes in pancreas, such as pancreatic and duodenal homeobox factor-1 (Pdx1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) and glucose transporter 2 (Glut2) were decreased significantly compared with those of normal control group. High-fat diet feeding during pregnancy may induce insulin resistance in maternal rats by inhibiting pancreatic Pax6 and its target genes expression.

High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice

NARCIS (Netherlands)

Xiao, Liang; Sonne, Si Brask; Feng, Qiang; Chen, Ning; Xia, Zhongkui; Li, Xiaoping; Fang, Zhiwei; Zhang, Dongya; Fjære, Even; Midtbø, Lisa Kolden; Derrien, Muriel; Hugenholtz, Floor; Tang, Longqing; Li, Junhua; Zhang, Jianfeng; Liu, Chuan; Hao, Qin; Vogel, Ulla Birgitte; Mortensen, Alicja; Kleerebezem, Michiel; Licht, Tine Rask; Yang, Huanming; Wang, Jian; Li, Yingrui; Arumugam, Manimozhiyan; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

2017-01-01

BACKGROUND: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those

Effects of high-fat diet exposure on learning & memory.

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Cordner, Zachary A; Tamashiro, Kellie L K

2015-12-01

The associations between consumption of a high-fat or 'Western' diet and metabolic disorders such as obesity, diabetes, and cardiovascular disease have long been recognized and a great deal of evidence now suggests that diets high in fat can also have a profound impact on the brain, behavior, and cognition. Here, we will review the techniques most often used to assess learning and memory in rodent models and discuss findings from studies assessing the cognitive effects of high-fat diet consumption. The review will then consider potential underlying mechanisms in the brain and conclude by reviewing emerging literature suggesting that maternal consumption of a high-fat diet may have effects on the learning and memory of offspring. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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Sunhye Shin

2018-02-01

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

Antihyperlipidemic Effects of Sesamum indicum L. in Rabbits Fed a High-Fat Diet

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Sedigheh Asgary

2013-01-01

Full Text Available The present study aimed to investigate the anti-hyperlipidemic effects of sesame in a high-fat fed rabbit model. Animals were randomly divided into four groups of eight animals each for 60 days as follows: normal diet, hypercholesterolemic diet (1% cholesterol, hypercholesterolemic diet (1% cholesterol + sesame seed (10%, and hypercholesterolemic diet (1% cholesterol + sesame oil (5%. Serum concentrations of total cholesterol, LDL-C, HDL-C, triglycerides, apoA and apoB, SGOT, SGPT, glucose and insulin were measured at the end of supplementation period in all studied groups. Hypercholesterolemic feeding resulted in a significant elevation of TC, TG, LDL-C, HDL-C, SGOT and SGPT as compared to the normocholesterolemic diet group (P0.05. In contrast, rabbits supplemented with sesame oil were found to have lower circulating concentrations of TC, LDL-C, HDL-C, SGOT and SGPT (P0.05. Supplementation with sesame oil, but not sesame seed, can ameliorate serum levels of lipids and hepatic enzymes in rabbits under a high-fat diet.

Feeding a high-concentrate corn straw diet induced epigenetic alterations in the mammary tissue of dairy cows.

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Guozhong Dong

Full Text Available The objective of this study was to investigate the effects of feeding a high-concentrate corn straw (HCS diet (65% concentrate+35% corn straw on the epigenetic changes in the mammary tissue of dairy cows in comparison with a low-concentrate corn straw (LCS diet (46% concentrate+54% corn straw and with a low-concentrate mixed forage (LMF diet (46% concentrate+54% mixed forage.Multiparous mid-lactation Chinese Holstein cows were fed one of these three diets for 6 weeks, at which time blood samples and mammary tissue samples were collected. Mammary arterial and venous blood samples were analyzed for lipopolysaccharide (LPS concentrations while mammary tissue samples were assayed for histone H3 acetylation and the methylation of specific genes associated with fat and protein synthesis.Extraction of histones and quantification of histone H3 acetylation revealed that acetylation was significantly reduced in cows fed the HCS diet, as compared with cows fed the LCS diet. Cows fed the HCS diet had significantly higher LPS concentrations in the mammary arterial blood, as compared with cows fed the LCS diet. We found that the extent of histone H3 acetylation was negatively correlated with LPS concentrations. The methylation of the stearoyl-coenzyme A desaturase gene associated with milk fat synthesis was increased in cows fed the HCS diet. By contrast, methylation of the gene encoding the signal transducer and activator of transcription 5A was reduced in cows fed the HCS diet, suggesting that feeding a high-concentrate corn straw diet may alter the methylation of specific genes involved in fat and protein synthesis in the mammary tissue of dairy cows.Feeding the high-concentrate diet induced epigenetic changes in the mammary tissues of dairy cows, possibly through effecting the release of differing amounts of LPS into the mammary blood.

Blueberry supplementation improves memory in middle-aged mice fed a high-fat diet.

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Carey, Amanda N; Gomes, Stacey M; Shukitt-Hale, Barbara

2014-05-07

Consuming a high-fat diet may result in behavioral deficits similar to those observed in aging animals. It has been demonstrated that blueberry supplementation can allay age-related behavioral deficits. To determine if supplementation of a high-fat diet with blueberries offers protection against putative high-fat diet-related declines, 9-month-old C57Bl/6 mice were maintained on low-fat (10% fat calories) or high-fat (60% fat calories) diets with and without 4% freeze-dried blueberry powder. Novel object recognition memory was impaired by the high-fat diet; after 4 months on the high-fat diet, mice spent 50% of their time on the novel object in the testing trial, performing no greater than chance performance. Blueberry supplementation prevented recognition memory deficits after 4 months on the diets, as mice on this diet spent 67% of their time on the novel object. After 5 months on the diets, mice consuming the high-fat diet passed through the platform location less often than mice on low-fat diets during probe trials on days 2 and 3 of Morris water maze testing, whereas mice consuming the high-fat blueberry diet passed through the platform location as often as mice on the low-fat diets. This study is a first step in determining if incorporating more nutrient-dense foods into a high-fat diet can allay cognitive dysfunction.

Comparison of hydrogenated vegetable shortening and nutritionally complete high fat diet on limited access-binge behavior in rats

OpenAIRE

Davis, Jon F.; Melhorn, Susan J.; Heiman, Justin U.; Tschöp, Matthias H.; Clegg, Deborah J.; Benoit, Stephen C.

2007-01-01

Previous studies have suggested that intermittent exposure to hydrogenated vegetable shortening yields a binge/compensate pattern of feeding in rats. The present study was designed to assess whether rats would exhibit similar patterns of intake when given intermittent access to a nutritionally complete high-fat diet. Four groups of rats received varying exposure to either hydrogenated vegetable shortening or high-fat diet for 8 consecutive weeks. Animals were given daily and intermittent acce...

Ameliorative effect of vitamin E on hepatic oxidative stress and hypoimmunity induced by high-fat diet in turbot (Scophthalmus maximus).

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Jia, Yudong; Jing, Qiqi; Niu, Huaxin; Huang, Bin

2017-08-01

This study was conducted to examine the effects of vitamin E on growth performance, oxidative stress and non-specific immunity of turbot (Scophthalmus maximus) fed with high-fat diet. Results showed that high-fat diet significantly increased hepatosomatic index, viscerosomatic index, hepatic malondialdehyde level and decreased catalase and superoxide dismutase activities, whereas final weight, specific growth rate and survival rate remained unchanged. Meanwhile, nitro blue tetrazolium positive leucocytes of head kidney, respiratory burst activity in head-kidney macrophage, phagocytic index and serum lysozyme activity were significantly reduced after feeding with high-fat diet. Furthermore, fish fed with high-fat diet promoted higher expression of heat shock protein (hsp70, hsp90), and inhibited expression of complement component 3 (c3) in the liver and tumor necrosis factor-α (tnf-α), interleukine 1β (il-1β), toll like receptor 22 (tlr-22) in the spleen and head-kidney, respectively. However, simultaneous supplementation with 480 mg kg -1 vitamin E protected turbot against high-fat diet-induced hepatic oxidative stress, hypoimmunity through attenuating lipid peroxidation, renewing antioxidant enzymes activities and nonspecific immune responses, and modulating the expression of stress protein (hsp70, hsp90) and immune-related genes (c3, tnf-α, il-1β, tlr-22). In conclusion, the obtained results indicate the vitamin E as a wildly used functional feed additive contributes potentially to alleviate high-fat diet-induced hepatic oxidative stress and hypoimmunity, maintain the health, and improve the broodstock management for turbot. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatic mitochondrial energetics during catch-up fat with high-fat diets rich in lard or safflower oil.

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Crescenzo, Raffaella; Bianco, Francesca; Falcone, Italia; Tsalouhidou, Sofia; Yepuri, Gayathri; Mougios, Vassilis; Dulloo, Abdul G; Liverini, Giovanna; Iossa, Susanna

2012-09-01

We have investigated whether altered hepatic mitochondrial energetics could explain the differential effects of high-fat diets with low or high ω6 polyunsaturated fatty acid content (lard vs. safflower oil) on the efficiency of body fat recovery (catch-up fat) during refeeding after caloric restriction. After 2 weeks of caloric restriction, rats were isocalorically refed with a low-fat diet (LF) or high-fat diets made from either lard or safflower oil for 1 week, and energy balance and body composition changes were assessed. Hepatic mitochondrial energetics were determined from measurements of liver mitochondrial mass, respiratory capacities, and proton leak. Compared to rats refed the LF, the groups refed high-fat diets showed lower energy expenditure and increased efficiency of fat gain; these differences were less marked with high-safflower oil than with high-lard diet. The increase in efficiency of catch-up fat by the high-fat diets could not be attributed to differences in liver mitochondrial activity. By contrast, the lower fat gain with high-safflower oil than with high-lard diet is accompanied by higher mitochondrial proton leak and increased proportion of arachidonic acid in mitochondrial membranes. In conclusion, the higher efficiency for catch-up fat on high-lard diet than on LF cannot be explained by altered hepatic mitochondrial energetics. By contrast, the ability of the high-safflower oil diet to produce a less pronounced increase in the efficiency of catch-up fat may partly reside in increased incorporation of arachidonic acid in hepatic mitochondrial membranes, leading to enhanced proton leak and mitochondrial uncoupling.

An 8-Week Ketogenic Low Carbohydrate, High Fat Diet Enhanced Exhaustive Exercise Capacity in Mice.

Science.gov (United States)

Ma, Sihui; Huang, Qingyi; Yada, Koichi; Liu, Chunhong; Suzuki, Katsuhiko

2018-05-25

Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD) is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.

An 8-Week Ketogenic Low Carbohydrate, High Fat Diet Enhanced Exhaustive Exercise Capacity in Mice

Directory of Open Access Journals (Sweden)

Sihui Ma

2018-05-01

Full Text Available Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.

Fructo-oligosaccharides reduce energy intake but do not affect adiposity in rats fed a low-fat diet but increase energy intake and reduce fat mass in rats fed a high-fat diet.

Science.gov (United States)

Hadri, Zouheyr; Rasoamanana, Rojo; Fromentin, Gilles; Azzout-Marniche, Dalila; Even, Patrick C; Gaudichon, Claire; Darcel, Nicolas; Bouras, Abdelkader Dilmi; Tomé, Daniel; Chaumontet, Catherine

2017-12-01

The ingestion of low or high lipid diets enriched with fructo-oligosaccharide (FOS) affects energy homeostasis. Ingesting protein diets also induces a depression of energy intake and decreases body weight. The goal of this study was to investigate the ability of FOS, combined or not with a high level of protein (P), to affect energy intake and body composition when included in diets containing different levels of lipids (L). We performed two studies of similar design over a period of 5weeks. During the first experiment (exp1), after a 3-week period of adaptation to a normal protein-low fat diet, the rats received one of the following four diets for 5weeks (6 rats per group): (i) normal protein (14% P/E (Energy) low fat (10% L/E) diet, (ii) normal protein, low fat diet supplemented with 10% FOS, (iii) high protein (55%P/E) low fat diet, and (iv) high protein, low fat diet supplemented with 10% FOS. In a second experiment (exp2) after the 3-week period of adaptation to a normal protein-high fat diet, the rats received one of the following 4 diets for 5weeks (6 rats per group): (i) normal protein, high fat diet (35% of fat), (ii) normal protein, high fat diet supplemented with 10% FOS, (iii) high protein high fat diet and (iv) high protein high fat diet supplemented with 10% FOS. In low-fat fed rats, FOS did not affect lean body mass (LBM) and fat mass but the protein level reduced fat mass and tended to reduce adiposity. In high-fat fed rats, FOS did not affect LBM but reduced fat mass and adiposity. No additive or antagonistic effects between FOS and the protein level were observed. FOS reduced energy intake in low-fat fed rats, did not affect energy intake in normal-protein high-fat fed rats but surprisingly, and significantly, increased energy intake in high-protein high-fat fed rats. The results thus showed that FOS added to a high-fat diet reduced body fat and body adiposity. Published by Elsevier Inc.

High-Fat, High-Sugar Diet-Induced Subendothelial Matrix Stiffening is Mitigated by Exercise.

Science.gov (United States)

Kohn, Julie C; Azar, Julian; Seta, Francesca; Reinhart-King, Cynthia A

2018-03-01

Consumption of a high-fat, high-sugar diet and sedentary lifestyle are correlated with bulk arterial stiffening. While measurements of bulk arterial stiffening are used to assess cardiovascular health clinically, they cannot account for changes to the tissue occurring on the cellular scale. The compliance of the subendothelial matrix in the intima mediates vascular permeability, an initiating step in atherosclerosis. High-fat, high-sugar diet consumption and a sedentary lifestyle both cause micro-scale subendothelial matrix stiffening, but the impact of these factors in concert remains unknown. In this study, mice on a high-fat, high-sugar diet were treated with aerobic exercise or returned to a normal diet. We measured bulk arterial stiffness through pulse wave velocity and subendothelial matrix stiffness ex vivo through atomic force microscopy. Our data indicate that while diet reversal mitigates high-fat, high-sugar diet-induced macro- and micro-scale stiffening, exercise only significantly decreases micro-scale stiffness and not macro-scale stiffness, during the time-scale studied. These data underscore the need for both healthy diet and exercise to maintain vascular health. These data also indicate that exercise may serve as a key lifestyle modification to partially reverse the deleterious impacts of high-fat, high-sugar diet consumption, even while macro-scale stiffness indicators do not change.

Hypothalamic gliosis associated with high-fat diet feeding is reversible in mice: a combined immunohistochemical and magnetic resonance imaging study.

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Berkseth, Kathryn E; Guyenet, Stephan J; Melhorn, Susan J; Lee, Donghoon; Thaler, Joshua P; Schur, Ellen A; Schwartz, Michael W

2014-08-01

Gliosis, the activation of astrocyte and microglial cell populations, is a hallmark of central nervous system injury and is detectable using either immunohistochemistry or in vivo magnetic resonance imaging (MRI). Obesity in rodents and humans is associated with gliosis of the arcuate nucleus, a key hypothalamic region for the regulation of energy homeostasis and adiposity, but whether this response is permanent or reversible is unknown. Here we combine terminal immunohistochemistry analysis with serial, noninvasive MRI to characterize the progression and reversibility of hypothalamic gliosis in high-fat diet (HFD)-fed mice. The effects of HFD feeding for 16 weeks to increase body weight and adiposity relative to chow were nearly normalized after the return to chow feeding for an additional 4 weeks in the diet-reversal group. Mice maintained on the HFD for the full 20-week study period experienced continued weight gain associated with the expected increases of astrocyte and microglial activation in the arcuate nucleus, but these changes were not observed in the diet-reversal group. The proopiomelanocortin neuron number did not differ between groups. Although MRI demonstrated a positive correlation between body weight, adiposity, and the gliosis-associated T2 signal in the mediobasal hypothalamus, it did not detect the reversal of gliosis among the HFD-fed mice after the return to chow diet. We conclude that hypothalamic gliosis associated with 16-week HFD feeding is largely reversible in rodents, consistent with the reversal of the HFD-induced obesity phenotype, and extend published evidence regarding the utility of MRI as a tool for studying obesity-associated hypothalamic gliosis in vivo.

Carbohydrate-restricted diets high in either monounsaturated fat or protein are equally effective at promoting fat loss and improving blood lipids.

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Luscombe-Marsh, Natalie D; Noakes, Manny; Wittert, Gary A; Keogh, Jennifer B; Foster, Paul; Clifton, Peter M

2005-04-01

When substituted for carbohydrate in an energy-reduced diet, dietary protein enhances fat loss in women. It is unknown whether the effect is due to increased protein or reduced carbohydrate. We compared the effects of 2 isocaloric diets that differed in protein and fat content on weight loss, lipids, appetite regulation, and energy expenditure after test meals. This was a parallel, randomized study in which subjects received either a low-fat, high-protein (LF-HP) diet (29 +/- 1% fat, 34 +/- 0.8% protein) or a high-fat, standard-protein (HF-SP) diet (45 +/- 0.6% fat, 18 +/- 0.3% protein) during 12 wk of energy restriction (6 +/- 0.1 MJ/d) and 4 wk of energy balance (7.4 +/- 0.3 MJ/d). Fifty-seven overweight and obese [mean body mass index (in kg/m(2)): 33.8 +/- 0.9] volunteers with insulin concentrations >12 mU/L completed the study. Weight loss (LF-HP group, 9.7 +/- 1.1 kg; HF-SP group, 10.2 +/- 1.4 kg; P = 0.78) and fat loss were not significantly different between diet groups even though the subjects desired less to eat after the LF-HP meal (P = 0.02). The decrease in resting energy expenditure was not significantly different between diet groups (LF-HP, -342 +/- 185 kJ/d; HF-SP, -349 +/- 220 kJ/d). The decrease in the thermic effect of feeding with weight loss was smaller in the LF-HP group than in the HF-SP group (-0.3 +/- 1.0% compared with -3.6 +/- 0.7%; P = 0.014). Glucose and insulin responses to test meals improved after weight loss (P loss and the improvements in insulin resistance and cardiovascular disease risk factors did not differ significantly between the 2 diets, and neither diet had any detrimental effects on bone turnover or renal function.

High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice.

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Xiao, Liang; Sonne, Si Brask; Feng, Qiang; Chen, Ning; Xia, Zhongkui; Li, Xiaoping; Fang, Zhiwei; Zhang, Dongya; Fjære, Even; Midtbø, Lisa Kolden; Derrien, Muriel; Hugenholtz, Floor; Tang, Longqing; Li, Junhua; Zhang, Jianfeng; Liu, Chuan; Hao, Qin; Vogel, Ulla Birgitte; Mortensen, Alicja; Kleerebezem, Michiel; Licht, Tine Rask; Yang, Huanming; Wang, Jian; Li, Yingrui; Arumugam, Manimozhiyan; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

2017-04-08

It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity. Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice. The changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.

High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice

DEFF Research Database (Denmark)

Xiao, Liang; Sonne, Si Brask; Feng, Qiang

2017-01-01

feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF......Background: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those......-induced obesity, but in Sv129 mice accentuates obesity.Results: Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF...

High fat diet alters lactation outcomes: possible involvement of inflammatory and serotonergic pathways.

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Laura L Hernandez

Full Text Available Delay in the onset of lactogenesis has been shown to occur in women who are obese, however the mechanism altered within the mammary gland causing the delay remains unknown. Consumption of high fat diets (HFD has been previously determined to result decreased litters and litter numbers in rodent models due to a decrease in fertility. We examined the effects of feeding a HFD (60% kcal from fat diet versus a low-fat diet (LFD; 10% kcal from fat to female Wistar rats on lactation outcomes. Feeding of HFD diet resulted in increased pup weights compared to pups from LFD fed animals for 4 d post-partum. Lactation was delayed in mothers on HFD but they began to produce copious milk volumes beginning 2 d post-partum, and milk yield was similar to LFD by day 3. Mammary glands collected from lactating animals on HFD diet, displayed a disrupted morphologies, with very few and small alveoli. Consistently, there was a significant decrease in the mRNA expression of milk protein genes, glucose transporter 1 (GLUT1 and keratin 5 (K5, a luminobasal cell marker in the mammary glands of HFD lactating animals. Expression of tryptophan hydroxylase 1 (TPH1, the rate-limiting enzyme in serotonin (5-HT biosynthesis, and the 5-HT(7 receptor (HTR7, which regulates mammary gland involution, were significantly increased in mammary glands of HFD animals. Additionally, we saw elevation of the inflammatory markers interleukin-6 (IL-6 and tumor necrosis factor-α (TNF- α. These results indicate that consumption of HFD impairs mammary parenchymal tissue and impedes its ability to synthesize and secrete milk, possibly through an increase in 5-HT production within the mammary gland leading to an inflammatory process.

High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia.

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Baufeld, Caroline; Osterloh, Anja; Prokop, Stefan; Miller, Kelly R; Heppner, Frank L

2016-09-01

Diets high in fat (HFD) are known to cause an immune response in the periphery as well as the central nervous system. In peripheral adipose tissue, this immune response is primarily mediated by macrophages that are recruited to the tissue. Similarly, reactivity of microglia, the innate immune cells of the brain, has been shown to occur in the hypothalamus of mice fed a high-fat diet. To characterize the nature of the microglial response to diets high in fat in a temporal fashion, we studied the phenotypic spectrum of hypothalamic microglia of mice fed high-fat diet for 3 days and 8 weeks by assessing their tissue reaction and inflammatory signature. While we observed a significant increase in Iba1+ myeloid cells and a reaction of GFAP+ astrocytes in the hypothalamus after 8 weeks of HFD feeding, we found the hypothalamic myeloid cell reaction to be limited to endogenous microglia and not mediated by infiltrating myeloid cells. Moreover, obese humans were found to present with signs of hypothalamic gliosis and exacerbated microglia dystrophy, suggesting a targeted microglia response to diet in humans as well. Notably, the glial reaction occurring in the mouse hypothalamus was not accompanied by an increase in pro-inflammatory cytokines, but rather by an anti-inflammatory reaction. Gene expression analyses of isolated microglia not only confirmed this observation, but also revealed a downregulation of microglia genes important for sensing signals in the microenvironment. Finally, we demonstrate that long-term exposure of microglia to HFD in vivo does not impair the cell's ability to respond to additional stimuli, like lipopolysaccharide. Taken together, our findings support the notion that microglia react to diets high in fat in a region-specific manner in rodents as well as in humans; however, this response changes over time as it is not exclusively pro-inflammatory nor does exposure to HFD prime microglia in the hypothalamus.

A high-fat diet and NAD+ activate sirt1 to rescue premature aging in cockayne syndrome

DEFF Research Database (Denmark)

Scheibye-Knudsen, Morten; Mitchell, Sarah J.; Fang, Evandro F.

2014-01-01

-fat, caloric-restricted, or resveratrol-supplemented diet. High-fat feeding rescued the metabolic, transcriptomic, and behavioral phenotypes of Csbm/m mice. Furthermore, premature aging in CS mice, nematodes, and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased......Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair proteins CS group A or B (CSA or CSB). Since dietary interventions can alter neurodegenerative processes, Csbm/m mice were given a high...... SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet, and β-hydroxybutyrate, PARP inhibition, or NAD+ supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB can displace activated PARP1 from damaged DNA...

Red Cabbage Microgreens Lower Circulating Low-Density Lipoprotein (LDL), Liver Cholesterol, and Inflammatory Cytokines in Mice Fed a High-Fat Diet.

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Huang, Haiqiu; Jiang, Xiaojing; Xiao, Zhenlei; Yu, Lu; Pham, Quynhchi; Sun, Jianghao; Chen, Pei; Yokoyama, Wallace; Yu, Liangli Lucy; Luo, Yaguang Sunny; Wang, Thomas T Y

2016-12-07

Cardiovascular disease (CVD) is the leading cause of death in the United States, and hypercholesterolemia is a major risk factor. Population studies, as well as animal and intervention studies, support the consumption of a variety of vegetables as a means to reduce CVD risk through modulation of hypercholesterolemia. Microgreens of a variety of vegetables and herbs have been reported to be more nutrient dense compared to their mature counterparts. However, little is known about the effectiveness of microgreens in affecting lipid and cholesterol levels. The present study used a rodent diet-induced obesity (DIO) model to address this question. C57BL/6NCr mice (n = 60, male, 5 weeks old) were randomly assigned to six feeding groups: (1) low-fat diet; (2) high-fat diet; (3) low-fat diet + 1.09% red cabbage microgreens; (4) low-fat diet + 1.66% mature red cabbage; (5) high-fat diet + 1.09% red cabbage microgreens; (6) high-fat diet + 1.66% mature red cabbage. The animals were on their respective diets for 8 weeks. We found microgreen supplementation attenuated high-fat diet induced weight gain. Moreover, supplementation with microgreens significantly lowered circulating LDL levels in animals fed the high-fat diet and reduced hepatic cholesterol ester, triacylglycerol levels, and expression of inflammatory cytokines in the liver. These data suggest that microgreens can modulate weight gain and cholesterol metabolism and may protect against CVD by preventing hypercholesterolemia.

Effect of a high-fat-high-cholesterol diet on gallbladder bile acid composition and gallbladder motility in dogs.

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Kakimoto, Toshiaki; Kanemoto, Hideyuki; Fukushima, Kenjiro; Ohno, Koichi; Tsujimoto, Hajime

2017-12-01

OBJCTIVE To investigate the effects of dietary lipid overload on bile acid metabolism and gallbladder motility in healthy dogs. ANIMALS 7 healthy Beagles. PROCEDURES In a crossover study, dogs were fed a high-fat-high-cholesterol diet (HFCD) or a low-fat diet (LFD) for a period of 2 weeks. After a 4-month washout period, dogs were fed the other diet for 2 weeks. Before and at the end of each feeding period, the concentrations of each of the gallbladder bile acids, cholecystokinin (CCK)-induced gallbladder motility, and bile acid metabolism-related hepatic gene expression were examined in all dogs. RESULTS The HFCD significantly increased plasma total cholesterol concentrations. The HFCD also increased the concentration of taurochenodeoxycholic acid and decreased the concentration of taurocholic acid in bile and reduced gallbladder contractility, whereas the LFD significantly decreased the concentration of taurodeoxycholic acid in bile. Gene expression analysis revealed significant elevation of cholesterol 7α-hydroxylase mRNA expression after feeding the HFCD for 2 weeks, but the expression of other genes was unchanged. CONCLUSIONS AND CLINICAL RELEVANCE Feeding the HFCD and LFD for 2 weeks induced changes in gallbladder bile acid composition and gallbladder motility in dogs. In particular, feeding the HFCD caused an increase in plasma total cholesterol concentration, an increase of hydrophobic bile acid concentration in bile, and a decrease in gallbladder sensitivity to CCK. These results suggested that similar bile acid compositional changes and gallbladder hypomotility might be evident in dogs with hyperlipidemia.

Effects of a free-choice high-fat high-sugar diet on brain PER2 and BMAL1 protein expression in mice.

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Blancas-Velazquez, Aurea; la Fleur, Susanne E; Mendoza, Jorge

2017-10-01

The suprachiasmatic nucleus (SCN) times the daily rhythms of behavioral processes including feeding. Beyond the SCN, the hypothalamic arcuate nucleus (ARC), involved in feeding regulation and metabolism, and the epithalamic lateral habenula (LHb), implicated in reward processing, show circadian rhythmic activity. These brain oscillators are functionally coupled to coordinate the daily rhythm of food intake. In rats, a free choice high-fat high-sugar (fcHFHS) diet leads to a rapid increase of calorie intake and body weight gain. Interestingly, under a fcHFHS condition, rats ingest a similar amount of sugar during day time (rest phase) as during night time (active phase), but keep the rhythmic intake of regular chow-food. The out of phase between feeding patterns of regular (chow) and highly rewarding food (sugar) may involve alterations of brain circadian oscillators regulating feeding. Here, we report that the fcHFHS diet is a successful model to induce calorie intake, body weight gain and fat tissue accumulation in mice, extending its effectiveness as previously reported in rats. Moreover, we observed that whereas in the SCN the day-night difference in the PER2 clock protein expression was similar between chow-fed and fcHFHS-fed animals, in the LHb, this day-night difference was altered in fcHFHS-exposed animals compared to control chow mice. These findings confirm previous observations in rats showing disrupted daily patterns of feeding behavior under a fcHFHS diet exposure, and extend our insights on the effects of the diet on circadian gene expression in brain clocks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of muscle fiber type composition on early fat accumulation under high-fat diet challenge.

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Hua, Ning; Takahashi, Hirokazu; Yee, Grace M; Kitajima, Yoichiro; Katagiri, Sayaka; Kojima, Motoyasu; Anzai, Keizo; Eguchi, Yuichiro; Hamilton, James A

2017-01-01

To investigate whether differences in muscle fiber types affect early-stage fat accumulation, under high fat diet challenge in mice. Twelve healthy male C57BL/6 mice experienced with short-term (6 weeks) diet treatment for the evaluation of early pattern changes in muscular fat. The mice were randomly divided into two groups: high fat diet (n = 8) and normal control diet (n = 4). Extra- and intra-myocellular lipid (EMCL and IMCL) in lumbar muscles (type I fiber predominant) and tibialis anterior (TA) muscle (type II fiber predominant) were determined using magnetic resonance spectroscopy (MRS). Correlation of EMCL, IMCL and their ratio between TA and lumbar muscles was evaluated. EMCL increased greatly in both muscle types after high fat diet. IMCL in TA and lumbar muscles increased to a much lower extent, with a slightly greater increase in TA muscles. EMCLs in the 2 muscles were positively correlated (r = 0.84, p = 0.01), but IMCLs showed a negative relationship (r = -0.84, p = 0.01). In lumbar muscles, high fat diet significantly decreased type I fiber while it increased type II fiber (all p≤0.001). In TA muscle, there was no significant fiber type shifting (p>0.05). Under short-time high fat diet challenge, lipid tends to initially accumulate extra-cellularly. In addition, compared to type II dominant muscle, Type I dominant muscle was less susceptible to IMCL accumulation but more to fiber type shifting. These phenomena might reflect compensative responses of skeletal muscle to dietary lipid overload in order to regulate metabolic homeostasis.

Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

International Nuclear Information System (INIS)

Yasuda-Yamahara, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi; Koya, Daisuke; Haneda, Masakzu; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

2015-01-01

Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding

Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

Energy Technology Data Exchange (ETDEWEB)

Yasuda-Yamahara, Mako [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan); Kume, Shinji, E-mail: skume@belle.shiga-med.ac.jp [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan); Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan); Koya, Daisuke [Department of Diabetology and Endocrinology, Kanazawa Medical University, Kahoku-Gun, Ishikawa (Japan); Haneda, Masakzu [Division of Metabolism and Biosystemic Science, Asahikawa Medical University, Asahikawa, Hokkaido (Japan); Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi [Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan)

2015-09-18

Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.

High fat, low carbohydrate diet limit fear and aggression in Göttingen minipigs

DEFF Research Database (Denmark)

Haagensen, Annika Maria Juul; Sørensen, Dorte Bratbo; Sandøe, Peter

2014-01-01

High fat, low carbohydrate diets have become popular, as short-term studies show that such diets are effective for reducing body weight, and lowering the risk of diabetes and cardiovascular disease. There is growing evidence from both humans and other animals that diet affects behaviour and intake...... of fat has been linked, positively and negatively, with traits such as exploration, social interaction, anxiety and fear. Animal models with high translational value can help provide relevant and important information in elucidating potential effects of high fat, low carbohydrate diets on human behaviour....... Twenty four young, male Göttingen minipigs were fed either a high fat/cholesterol, low carbohydrate diet or a low fat, high carbohydrate/sucrose diet in contrast to a standard low fat, high carbohydrate minipig diet. Spontaneous behaviour was observed through video recordings of home pens and test...

Increased expression of PPARγ in high fat diet-induced liver steatosis in mice

International Nuclear Information System (INIS)

Inoue, Mitsutaka; Ohtake, Takaaki; Motomura, Wataru; Takahashi, Nobuhiko; Hosoki, Yayoi; Miyoshi, Shigeki; Suzuki, Yasuaki; Saito, Hiroyuki; Kohgo, Yutaka; Okumura, Toshikatsu

2005-01-01

The present study was performed to examine a hypothesis that peroxisome proliferator-activated receptor γ (PPARγ) is implicated in high fat diet-induced liver steatosis. Mice were fed with control or high fat diet containing approximately 10% or 80% cholesterol, respectively. Macroscopic and microscopic findings demonstrated that lipid accumulation in the liver was observed as early as 2 weeks after high fat diet and that high fat diet for 12 weeks developed a fatty liver phenotype, establishing a novel model of diet-induced liver steatosis. Gene profiling with microarray and real-time PCR studies demonstrated that among genes involved in lipid metabolism, adipogenesis-related genes, PPARγ and its targeted gene, CD36 mRNA expression was specifically up-regulated in the liver by high fat diet for 2 weeks. Immunohistochemical study revealed that PPARγ protein expression is increased in the nuclei of hepatocytes by high fat diet. It was also shown that protein expression of cAMP response element-binding protein (CREB), an upstream molecule of PPARγ, in the liver was drastically suppressed by high fat diet. All these results suggest for the first time that the CREB-PPARγ signaling pathway may be involved in the high fat diet-induced liver steatosis

Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet

Directory of Open Access Journals (Sweden)

Alessandra Ferramosca

2015-01-01

Full Text Available In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group, a diet with 35% fat (HF group, or a high-fat diet supplemented with 2.5% krill oil (HF+KO group. The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism.

Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet.

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Ferramosca, Alessandra; Conte, Annalea; Zara, Vincenzo

2015-01-01

In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group), a diet with 35% fat (HF group), or a high-fat diet supplemented with 2.5% krill oil (HF+KO group). The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism.

High-saturated fat-sucrose feeding affects lactation energetics in control mice and mice selectively bred for high wheel-running behavior

NARCIS (Netherlands)

Guidotti, Stefano; Jonas, Izabella; Schubert, Kristin A.; Garland, Theodore; Meijer, Harro A. J.; Scheurink, Anton J. W.; van Dijk, Gertjan

2013-01-01

Feeding a diet high in fat and sucrose (HFS) during pregnancy and lactation is known to increase susceptibility to develop metabolic derangements later in life. A trait for increased behavioral activity may oppose these effects, since this would drain energy from milk produced to be made available

Moderate High Fat Diet Increases Sucrose Self-Administration In Young Rats

OpenAIRE

Figlewicz, Dianne P.; Jay, Jennifer L.; Acheson, Molly A.; Magrisso, Irwin J.; West, Constance H.; Zavosh, Aryana; Benoit, Stephen C.; Davis, Jon F.

2012-01-01

We have previously reported that a moderately high fat diet increases motivation for sucrose in adult rats. In this study, we tested the motivational, neurochemical, and metabolic effects of the high fat diet in male rats transitioning through puberty, during 5-8 weeks of age. We observed that the high fat diet increased motivated responding for sucrose, which was independent of either metabolic changes or changes in catecholamine neurotransmitter metabolites in the nucleus accumbens. However...

Inulin supplementation reduces the negative effect of a high-fat diet rich in SFA on bone health of growing pigs.

Science.gov (United States)

Sobol, Monika; Raj, Stanisława; Skiba, Grzegorz

2018-05-01

Consumption of a high-fat diet, rich in SFA, causes deterioration of bone properties. Some studies suggest that feeding inulin to animals may increase mineral absorption and positively affect bone quality; however, these studies have been carried out only on rodents fed a standard diet. The primary objective of this study was to determine the effect of inulin on bone health of pigs (using it as an animal model for humans) fed a high-fat diet rich in SFA, having an unbalanced ratio of lysine:metabolisable energy. It was hypothesised that inulin reduces the negative effects of such a diet on bone health. At 50 d of age, twenty-one pigs were randomly allotted to three groups: the control (C) group fed a standard diet, and two experimental (T and TI) groups fed a high-fat diet rich in SFA. Moreover, TI pigs consumed an extra inulin supply (7 % of daily feed intake). After 10 weeks, whole-body bone mineral content (P=0·0054) and bone mineral density (P=0·0322) were higher in pigs of groups TI and C compared with those of group T. Femur bone mineral density was highest in pigs in group C, lower in group TI and lowest in group T (P=0·001). Femurs of pigs in groups TI and C had similar, but higher, maximum strength compared with femurs of pigs in group T (P=0·0082). In conclusion, consumption of a high-fat diet rich in SFA adversely affected bone health, but inulin supplementation in such a diet diminishes this negative effect.

Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats

Directory of Open Access Journals (Sweden)

Sieglinde Zelzer

2015-05-01

Full Text Available Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66 were grouped into normal diet (n = 30 and high-fat diet (n = 36 groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3 treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL, malondialdehyde (MDA, 4-hydroxynonenal (HNE, the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats.

Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats.

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Zelzer, Sieglinde; Mangge, Harald; Pailer, Sabine; Ainoedhofer, Herwig; Kieslinger, Petra; Stojakovic, Tatjana; Scharnagl, Hubert; Prüller, Florian; Weghuber, Daniel; Datz, Christian; Haybaeck, Johannes; Obermayer-Pietsch, Barbara; Trummer, Christian; Gostner, Johanna; Gruber, Hans-Jürgen

2015-05-21

Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats.

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 ...

Purified blueberry anthocyanins and blueberry juice alter development of obesity in mice fed an obesogenic high-fat diet.

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Prior, Ronald L; E Wilkes, Samuel; R Rogers, Theodore; Khanal, Ramesh C; Wu, Xianli; Howard, Luke R

2010-04-14

Male C57BL/6J mice (25 days of age) were fed either a low-fat diet (10% kcal from fat) (LF) or a high-fat diet (45% kcal from fat) (HF45) for a period of 72 days. Blueberry juice or purified blueberry anthocyanins (0.2 or 1.0 mg/mL) in the drinking water were included in LF or HF45 treatments. Sucrose was added to the drinking water of one treatment to test if the sugars in blueberry juice would affect development of obesity. Total body weights (g) and body fat (%) were higher and body lean tissue (%) was lower in the HF45 fed mice compared to the LF fed mice after 72 days, but in mice fed HF45 diet plus blueberry juice or blueberry anthocyanins (0.2 mg/mL), body fat (%) was not different from those mice fed the LF diet. Anthocyanins (ACNs) decreased retroperitoneal and epididymal adipose tissue weights. Fasting serum glucose concentrations were higher in mice fed the HF45 diet. However, it was reduced to LF levels in mice fed the HF45 diet plus 0.2 mg of ACNs/mL in the drinking water, but not with blueberry juice. beta cell function (HOMA-BCF) score was lowered with HF45 feeding but returned to normal levels in mice fed the HF45 diet plus purified ACNs (0.2 mg/mL). Serum leptin was elevated in mice fed HF45 diet, and feeding either blueberry juice or purified ACNs (0.2 mg/mL) decreased serum leptin levels relative to HF45 control. Sucrose in drinking water, when consumption was restricted to the volume of juice consumed, produced lower serum leptin and insulin levels, leptin/fat, and retroperitoneal and total fat (% BW). Blueberry juice was not as effective as the low dose of anthocyanins in the drinking water in preventing obesity. Additional studies are needed to determine factors responsible for the differing responses of blueberry juice and whole blueberry in preventing the development of obesity.

High-fat diet-induced insulin resistance does not increase plasma anandamide levels or potentiate anandamide insulinotropic effect in isolated canine islets.

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Woolcott, Orison O; Richey, Joyce M; Kabir, Morvarid; Chow, Robert H; Iyer, Malini S; Kirkman, Erlinda L; Stefanovski, Darko; Lottati, Maya; Kim, Stella P; Harrison, L Nicole; Ionut, Viorica; Zheng, Dan; Hsu, Isabel R; Catalano, Karyn J; Chiu, Jenny D; Bradshaw, Heather; Wu, Qiang; Kolka, Cathryn M; Bergman, Richard N

2015-01-01

Obesity has been associated with elevated plasma anandamide levels. In addition, anandamide has been shown to stimulate insulin secretion in vitro, suggesting that anandamide might be linked to hyperinsulinemia. To determine whether high-fat diet-induced insulin resistance increases anandamide levels and potentiates the insulinotropic effect of anandamide in isolated pancreatic islets. Dogs were fed a high-fat diet (n = 9) for 22 weeks. Abdominal fat depot was quantified by MRI. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp. Fasting plasma endocannabinoid levels were analyzed by liquid chromatography-mass spectrometry. All metabolic assessments were performed before and after fat diet regimen. At the end of the study, pancreatic islets were isolated prior to euthanasia to test the in vitro effect of anandamide on islet hormones. mRNA expression of cannabinoid receptors was determined in intact islets. The findings in vitro were compared with those from animals fed a control diet (n = 7). Prolonged fat feeding increased abdominal fat content by 81.3±21.6% (mean±S.E.M, Pcanines, high-fat diet-induced insulin resistance does not alter plasma anandamide levels or further potentiate the insulinotropic effect of anandamide in vitro.

Effects of high fat diet on the basal activity of the hypothalamus- pituitary-adrenal axis in mice: A systematic review

NARCIS (Netherlands)

Auvinen, H.E.; Romijn, J.A.; Biermasz, N.R.; Havekes, L.M.; Smit, J.W.A.; Rensen, P.C.N.; Pereira, A.M.

2011-01-01

Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the

Non-fasting factor VII coagulant activity (FVII:C) increased by high-fat diet

DEFF Research Database (Denmark)

Bladbjerg, Else-Marie; Marckmann, P; Sandström, B

1994-01-01

:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII:Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet....... The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis. Udgivelsesdato: 1994-Jun......Preliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20...

Differential effects of high-carbohydrate and high-fat diets on hepatic lipogenesis in rats.

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Ferramosca, Alessandra; Conte, Annalea; Damiano, Fabrizio; Siculella, Luisa; Zara, Vincenzo

2014-06-01

Hepatic fatty acid synthesis is influenced by several nutritional and hormonal factors. In this study, we have investigated the effects of distinct experimental diets enriched in carbohydrate or in fat on hepatic lipogenesis. Male Wistar rats were divided into four groups and fed distinct experimental diets enriched in carbohydrates (70% w/w) or in fat (20 and 35% w/w). Activity and expression of the mitochondrial citrate carrier and of the cytosolic enzymes acetyl-CoA carboxylase and fatty acid synthetase were analyzed through the study with assessments at 0, 1, 2, 4, and 6 weeks. Liver lipids and plasma levels of lipids, glucose, and insulin were assayed in parallel. Whereas the high-carbohydrate diet moderately stimulated hepatic lipogenesis, a strong inhibition of this anabolic pathway was found in animals fed high-fat diets. This inhibition was time-dependent and concentration-dependent. Moreover, whereas the high-carbohydrate diet induced an increase in plasma triglycerides, the high-fat diets determined an accumulation of triglycerides in liver. An increase in the plasmatic levels of glucose and insulin was observed in all cases. The excess of sucrose in the diet is converted into fat that is distributed by bloodstream in the organism in the form of circulating triglycerides. On the other hand, a high amount of dietary fat caused a strong inhibition of lipogenesis and a concomitant increase in the level of hepatic lipids, thereby highlighting, in these conditions, the role of liver as a reservoir of exogenous fat.

Diet-induced impulsivity: Effects of a high-fat and a high-sugar diet on impulsive choice in rats.

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Steele, Catherine C; Pirkle, Jesseca R A; Kirkpatrick, Kimberly

2017-01-01

Impulsive choice is a common charactertistic among individuals with gambling problems, obesity, and substance abuse issues. Impulsive choice has been classified as a trans-disease process, and understanding the etiology of trait impulsivity could help to understand how diseases and disorders related to impulsive choice are manifested. The Western diet is a possible catalyst of impulsive choice as individuals who are obese and who eat diets high in fat and sugar are typically more impulsive. However, such correlational evidence is unable to discern the direction and causal nature of the relationship. The present study sought to determine how diet may directly contribute to impulsive choice. After 8 weeks of dietary exposure (high-fat, high-sugar, chow), the rats were tested on an impulsive choice task, which presented choices between a smaller-sooner reward (SS) and a larger-later reward (LL). Then, the rats were transferred to a chow diet and retested on the impulsive choice task. The high-sugar and high-fat groups made significantly more impulsive choices than the chow group. Both groups became more self-controlled when they were off the diet, but there were some residual effects of the diet on choice behavior. These results suggest that diet, specifically one high in processed fat or sugar, induces impulsive choice. This diet-induced impulsivity could be a precursor to other disorders that are characterized by impulsivity, such as diet-induced obesity, and could offer potential understanding of the trans-disease nature of impulsive choice.

Effect of high fat and high sugar diet on insulin binding and insulin action in isolated rat adipocytes

OpenAIRE

岡﨑,悟

1987-01-01

To clarify on a cellular basis the mechanism of the diabetogenic effect of the westernized diet, insulin binding, insulin stimulated 3-o-methylglucose uptake and glucose oxidation were studied in isolated adipocytes from rats fed experimental diets : low fat-no sugar diet (energy ratio of 10% fat, 70% starch, a model of the traditional Japanese diet), high fat-high sugar diet (40% fat, 20% starch, 20% sugar, a model of the westernized diet), low fat-high sugar diet (10% fat, 50% starch, 20% s...

High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice

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Xiao, Liang; Sonne, Si Brask; Feng, Qiang

2017-01-01

Background: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those...... associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet......-induced obesity, but in Sv129 mice accentuates obesity.Results: Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF...

High-fat diet feeding differentially affects the development of inflammation in the central nervous system

OpenAIRE

Guillemot-Legris, Owein; Masquelier, Julien; Everard, Amandine; Cani, Patrice D.; Al Houayek, Mireille; Muccioli, Giulio

2016-01-01

Background Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone. Methods We used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16?weeks) a group of ...

High fat, low carbohydrate diet limit fear and aggression in Göttingen minipigs.

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Annika Maria Juul Haagensen

Full Text Available High fat, low carbohydrate diets have become popular, as short-term studies show that such diets are effective for reducing body weight, and lowering the risk of diabetes and cardiovascular disease. There is growing evidence from both humans and other animals that diet affects behaviour and intake of fat has been linked, positively and negatively, with traits such as exploration, social interaction, anxiety and fear. Animal models with high translational value can help provide relevant and important information in elucidating potential effects of high fat, low carbohydrate diets on human behaviour. Twenty four young, male Göttingen minipigs were fed either a high fat/cholesterol, low carbohydrate diet or a low fat, high carbohydrate/sucrose diet in contrast to a standard low fat, high carbohydrate minipig diet. Spontaneous behaviour was observed through video recordings of home pens and test-related behaviours were recorded during tests involving animal-human contact and reaction towards a novel object. We showed that the minipigs fed a high fat/cholesterol, low carbohydrate diet were less aggressive, showed more non-agonistic social contact and had fewer and less severe skin lesions and were less fearful of a novel object than minipigs fed low fat, high carbohydrate diets. These results found in a porcine model could have important implications for general health and wellbeing of humans and show the potential for using dietary manipulations to reduce aggression in human society.

Chronic High Fat Diet Consumption Impairs Metabolic Health of Male Mice.

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Morselli, Eugenia; Criollo, Alfredo; Rodriguez-Navas, Carlos; Clegg, Deborah J

We show that chronic high fat diet (HFD) feeding affects the hypothalamus of male but not female mice. In our study we demonstrate that palmitic acid and sphingolipids accumulate in the central nervous system of HFD-fed males. Additionally, we show that HFD-feeding reduces proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) thus reducing estrogen receptor α (ERα) and driving hypothalamic inflammation in male but not female mice. Hypothalamic inflammation correlates with markers of metabolic dysregulation as indicated by dysregulation in glucose intolerance and myocardial function. Lastly, we demonstrate that there are blockages in mitophagy and lipophagy in hypothalamic tissues in males. Our data suggest there is a sexually dimorphic response to chronic HDF exposure, females; despite gaining the same amount of body weight following HFD-feeding, appear to be protected from the adverse metabolic effects of the HFD.

A Free-Choice High-Fat High-Sugar Diet Alters Day-Night Gene Expression in Reward-Related Brain Areas in Rats

NARCIS (Netherlands)

Blancas-Velazquez, Aurea Susana; Unmehopa, Unga A; Eggels, Leslie; Koekkoek, Laura L.; Kalsbeek, A.; Mendoza, Jorge; la Fleur, Susanne E

2018-01-01

Under normal light-dark conditions, nocturnal rodents consume most of their food during the dark period. Diets high in fat and sugar, however, may affect the day-night feeding rhythm resulting in a higher light phase intake. In vitro and in vivo studies showed that nutrients affect clock-gene

Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet

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Harald Mangge

2015-07-01

Full Text Available Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP, a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66 were grouped into normal diet (ND; n = 30 and high-fat diet (HFD; n = 36 groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3 treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increased—and hyperthyroid animals significantly decreased—ETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition.

Effects of a high-fat diet during pregnancy and lactation are modulated by E. coli in rat offspring.

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Fåk, F; Karlsson, C L J; Ahrné, S; Molin, G; Weström, B

2012-05-01

Microbial manipulations in early life can affect gut development and inflammatory status of the neonate. The maternal diet during pregnancy and lactation also influences the health of the offspring, but the impact of maternal high-fat (HF) feeding along with modulations of the gut microbiota on body weight, fat deposition and gut function in the offspring has been poorly studied. Rat dams were given access to either an HF or a standard low-fat diet during the last 2 weeks of pregnancy and during lactation and effects on body weight and gastrointestinal function were investigated in the 14-day-old offspring. To elucidate whether bacterial administration to the dam could modulate any effects of the diets in the rat pups, another group of dams were given Escherichia coli in their drinking water. Maternal HF feeding resulted in increased body and fat pad weights in the offspring, along with increased levels of the acute-phase protein, haptoglobin and decreased protein content and disaccharidase activities in the small intestine. The addition of E. coli further accentuated these responses in the young rats, which, in addition to higher body weights and increased fat deposition, also showed an increased intestinal permeability and elevated levels of haptoglobin. The present study demonstrates for the first time how bacterial administration to the maternal diet during the neonatal period can affect body weight and fat deposition in the offspring. The results point to a mechanistic link between the gut microbiota, increased intestinal permeability and metabolic endotoxemia, which appear to have led to increased adiposity in the young rats.

Fatty liver accompanies an increase of Lactobacillus acidophilus in the hind gut of C57/BL mice fed a high-fat diet

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High-fat diets can produce obesity and have been linked to the development of nonalcoholic fatty liver disease (NAFLD), which also induces changes in the gut microbiome. This study tested the hypothesis that high-fat feeding increases certain predominate hind gut bacteria in a C57BL/6 mouse model o...

High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway

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Napolitano Mariarosaria

2011-04-01

Full Text Available Abstract Background Hyperhomocysteinemia (HHcy causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD in rats were investigated. Methods and results After feeding rats a standard low fat diet (control or a high fat diet (57% metabolisable energy as fat for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS and cystathionine γ-lyase (CGS, the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group. Conclusions These results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.

Role of high-fat diet in stress response of Drosophila.

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Erilynn T Heinrichsen

Full Text Available Obesity is associated with many diseases, one of the most common being obstructive sleep apnea (OSA, which in turn leads to blood gas disturbances, including intermittent hypoxia (IH. Obesity, OSA and IH are associated with metabolic changes, and while much mammalian work has been done, mechanisms underlying the response to IH, the role of obesity and the interaction of obesity and hypoxia remain unknown. As a model organism, Drosophila offers tremendous power to study a specific phenotype and, at a subsequent stage, to uncover and study fundamental mechanisms, given the conservation of molecular pathways. Herein, we characterize the phenotype of Drosophila on a high-fat diet in normoxia, IH and constant hypoxia (CH using triglyceride and glucose levels, response to stress and lifespan. We found that female flies on a high-fat diet show increased triglyceride levels (p<0.001 and a shortened lifespan in normoxia, IH and CH. Furthermore, flies on a high-fat diet in normoxia and CH show diminished tolerance to stress, with decreased survival after exposure to extreme cold or anoxia (p<0.001. Of interest, IH seems to rescue this decreased cold tolerance, as flies on a high-fat diet almost completely recovered from cold stress following IH. We conclude that the cross talk between hypoxia and a high-fat diet can be either deleterious or compensatory, depending on the nature of the hypoxic treatment.

Effect of a high monounsaturated vs high polyunsaturated fat hypocaloric diets in nonalcoholic fatty liver disease.

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Aller, R; de Luis, D A; Izaola, O; de la Fuente, B; Bachiller, R

2014-01-01

Hyperaminotransferasemia is an important problem in obese patients. We decide to examine the changes in hyperaminotransferasemia after weight reduction in obese patients with and without NAFLD secondary to a high monounsaturated fat vs. a high polyunsaturated fat hypocaloric diets. A population of 306 obese patients was randomly allocated to two groups: Diet M (high monounsaturated fat hypocaloric diet) and Diet P (high polyunsaturated fat hypocaloric diet). Patients were classified as group I (obese subjects; n=262) when serum ALT activity was normal or group II (NAFLD patients; n=44) when serum ALT activity was (≥ 43 UI/L). In NAFLD group with diet M, BMI, weight, fat mass, waist circumference, systolic blood pressure, total cholesterol, LDL cholesterol), insulin and HOMA-R decreased. In NAFLD group with diet P, BMI, weight, fat mass, waist circumference, systolic blood pressure, total cholesterol, LDL cholesterol), insulin and HOMA-R decreased, too. In NAFLD group, alanine aminotransferase [(diet M) -20.3±19.2 UI/L vs. (diet P) -14.2±20.1 UI/L], aspartate aminotransferase [(diet M) -11.3±12.2 UI/L vs. (diet P) -11.1±10.1 UI/L], and gammaglutamyl transferase [(diet M) -18.1±12.2 UI/L vs. (diet P) -10.9±20.1 UI/L] improved with both diets. We showed that weight reduction secondary to two hypocaloric diets was associated with improvement in hypertransaminasemia and insulin resistance in NAFLD patients.

Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice.

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Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

2012-09-01

Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training.

RNA-Sequencing of Drosophila melanogaster Head Tissue on High-Sugar and High-Fat Diets

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Wayne Hemphill

2018-01-01

Full Text Available Obesity has been shown to increase risk for cardiovascular disease and type-2 diabetes. In addition, it has been implicated in aggravation of neurological conditions such as Alzheimer’s. In the model organism Drosophila melanogaster, a physiological state mimicking diet-induced obesity can be induced by subjecting fruit flies to a solid medium disproportionately higher in sugar than protein, or that has been supplemented with a rich source of saturated fat. These flies can exhibit increased circulating glucose levels, increased triglyceride content, insulin-like peptide resistance, and behavior indicative of neurological decline. We subjected flies to variants of the high-sugar diet, high-fat diet, or normal (control diet, followed by a total RNA extraction from fly heads of each diet group for the purpose of Poly-A selected RNA-Sequencing. Our objective was to identify the effects of obesogenic diets on transcriptome patterns, how they differed between obesogenic diets, and identify genes that may relate to pathogenesis accompanying an obesity-like state. Gene ontology analysis indicated an overrepresentation of affected genes associated with immunity, metabolism, and hemocyanin in the high-fat diet group, and CHK, cell cycle activity, and DNA binding and transcription in the high-sugar diet group. Our results also indicate differences in the effects of the high-fat diet and high-sugar diet on expression profiles in head tissue of flies, despite the reportedly similar phenotypic impacts of the diets. The impacted genes, and how they may relate to pathogenesis in the Drosophila obesity-like state, warrant further experimental investigation.

Effect of fitness on glucose, insulin and cortisol responses to diets varying in starch and fat content in Thoroughbred horses with recurrent exertional rhabdomyolysis.

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Finno, C J; McKenzie, E; Valberg, S J; Pagan, J

2010-11-01

Recurrent exertional rhabdomyolysis (RER) occurs in fit, nervous Thoroughbreds fed high nonstructural carbohydrate (NSC) diets. Clinical signs are diminished by feeding low NSC, high fat diets; however, the mechanism is unclear. To determine if the glucose, insulin and cortisol response to isocaloric diets varying in fat and NSC availability differ in fit vs. unfit Thoroughbreds with RER. Four fit (10 weeks treadmill training) RER Thoroughbred mares were exercised and fed 3 isocaloric (121 MJ/day) diets in a 5 day/diet block design. Two high NSC concentrates, sweet feed (SF) and a processed pelleted feed (PL) and a low starch high fat feed (FAT) were used. After 24 h of rest and a 12 h fast, horses ate half their daily concentrate. Blood sampled for [glucose], [insulin] and [cortisol] was obtained before, immediately after and at 30-60 min intervals for 420 min. After 3-6 months detraining period, the block design was repeated. Results for SF and PL were similar. Regardless of diet, cortisol was higher in fit vs. unfit horses. Fit horses on SF/PL had higher post prandial [insulin] and insulin:glucose ratio than unfit horses. FAT resulted in lower post prandial [glucose] and [insulin] vs. SF/PL. Higher [insulin] in fit vs. unfit horses was not seen on the FAT diet. Increased post prandial [glucose], [insulin] and [cortisol] induced by high NSC, but not high fat, feeds are enhanced by fitness in RER horses. This combination may trigger rhabdomyolysis through increased excitability in RER Thoroughbreds. © 2010 EVJ Ltd.

Sensory-specific satiety is intact in rats made obese on a high-fat high-sugar choice diet.

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Myers, Kevin P

2017-05-01

Sensory-specific satiety (SSS) is the temporary decreased pleasantness of a recently eaten food, which inhibits further eating. Evidence is currently mixed whether SSS is weaker in obese people, and whether such difference precedes or follows from the obese state. Animal models allow testing whether diet-induced obesity causes SSS impairment. Female rats (n = 24) were randomly assigned to an obesogenic high-fat, high-sugar choice diet or chow-only control. Tests of SSS involved pre-feeding a single palatable, distinctively-flavored food (cheese- or cocoa-flavored) prior to free choice between both foods. Rats were tested for short-term SSS (2 h pre-feeding immediately followed by 2 h choice) and long-term SSS (3 day pre-feeding prior to choice on day 4). In both short- and long-term tests rats exhibited SSS by shifting preference towards the food not recently eaten. SSS was not impaired in obese rats. On the contrary, in the long-term tests they showed stronger SSS than controls. This demonstrates that neither the obese state nor a history of excess energy consumption fundamentally causes impaired SSS in rats. The putative impaired SSS in obese people may instead reflect a specific predisposition, properties of the obesogenic diet, or history of restrictive dieting and bingeing. Copyright © 2017 Elsevier Ltd. All rights reserved.

High fat diet disrupts endoplasmic reticulum calcium homeostasis in the rat liver.

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Wires, Emily S; Trychta, Kathleen A; Bäck, Susanne; Sulima, Agnieszka; Rice, Kenner C; Harvey, Brandon K

2017-11-01

Disruption to endoplasmic reticulum (ER) calcium homeostasis has been implicated in obesity, however, the ability to longitudinally monitor ER calcium fluctuations has been challenging with prior methodologies. We recently described the development of a Gaussia luciferase (GLuc)-based reporter protein responsive to ER calcium depletion (GLuc-SERCaMP) and investigated the effect of a high fat diet on ER calcium homeostasis. A GLuc-based reporter cell line was treated with palmitate, a free fatty acid. Rats intrahepatically injected with GLuc-SERCaMP reporter were fed a cafeteria diet or high fat diet. The liver and plasma were examined for established markers of steatosis and compared to plasma levels of SERCaMP activity. Palmitate induced GLuc-SERCaMP release in vitro, indicating ER calcium depletion. Consumption of a cafeteria diet or high fat pellets correlated with alterations to hepatic ER calcium homeostasis in rats, shown by increased GLuc-SERCaMP release. Access to ad lib high fat pellets also led to a corresponding decrease in microsomal calcium ATPase activity and an increase in markers of hepatic steatosis. In addition to GLuc-SERCaMP, we have also identified endogenous proteins (endogenous SERCaMPs) with a similar response to ER calcium depletion. We demonstrated the release of an endogenous SERCaMP, thought to be a liver esterase, during access to a high fat diet. Attenuation of both GLuc-SERCaMP and endogenous SERCaMP was observed during dantrolene administration. Here we describe the use of a reporter for in vitro and in vivo models of high fat diet. Our results support the theory that dietary fat intake correlates with a decrease in ER calcium levels in the liver and suggest a high fat diet alters the ER proteome. Lay summary: ER calcium dysregulation was observed in rats fed a cafeteria diet or high fat pellets, with fluctuations in sensor release correlating with fat intake. Attenuation of sensor release, as well as food intake was observed during

Effects of N,N-dimethylglycine sodium salt on apparent digestibility, vitamin E absorption, and serum proteins in broiler chickens fed a high- or low-fat diet.

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Prola, L; Nery, J; Lauwaerts, A; Bianchi, C; Sterpone, L; De Marco, M; Pozzo, L; Schiavone, A

2013-05-01

The objective of this study was to assess the effect of supplementation with sodium salt of N,N-dimethylglycine (DMG-Na) on apparent digestibility (AD) in broiler chickens fed low- and high-fat diets. Twenty-eight 1-d-old broiler chickens were fed one of the dietary treatments: a low-fat diet (LF) or a high-fat diet (HF) supplemented with or without 1,000 mg/kg of DMG-Na. Body weight and feed consumption were recorded at 14 and 35 d of age. Average daily growth, daily feed intake, and feed conversion ratio were calculated. The AD of DM, organic matter (OM), CP, total fat (TF), and α-tocopheryl-acetate were assessed by 2 digestibility trials (at 18-21 and 32-35 d, respectively). Serum protein and plasma α-tocopherol concentrations were assessed at 35 d of age. Final BW, feed intake, carcass, breast, and spleen weight were higher in groups fed LF than HF diets (P = 0.048, P = 0.002, P = 0.039, P DMG-Na-unsupplemented groups (P = 0.011) for both fat levels. During the first digestibility trial (18-21 d), the AD of DM (P = 0.023), OM (P = 0.033), CP (P = 0.030), and α-tocopheryl-acetate (P = 0.036) was higher in the DMG-Na-supplemented group than control. Digestibility of total fat was increased by DMG-Na supplementation in the LF groups (P = 0.038). A trend for improvement of digestibility was observed during the second digestibility trial (32-35 d) for DM (P = 0.089), OM (P = 0.051), and CP (P = 0.063) in DMG-Na groups. Total serum proteins (and relative fractions) were positively influenced by DMG-Na supplementation both in LF and HF diets (P = 0.029). Plasma α-tocopherol concentration was higher in groups fed LF than HF diets (P < 0.001).

Induction of ketosis in rats fed low-carbohydrate, high-fat diets depends on the relative abundance of dietary fat and protein.

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Bielohuby, Maximilian; Menhofer, Dominik; Kirchner, Henriette; Stoehr, Barbara J M; Müller, Timo D; Stock, Peggy; Hempel, Madlen; Stemmer, Kerstin; Pfluger, Paul T; Kienzle, Ellen; Christ, Bruno; Tschöp, Matthias H; Bidlingmaier, Martin

2011-01-01

Low-carbohydrate/high-fat diets (LC-HFDs) in rodent models have been implicated with both weight loss and as a therapeutic approach to treat neurological diseases. LC-HFDs are known to induce ketosis; however, systematic studies analyzing the impact of the macronutrient composition on ketosis induction and weight loss success are lacking. Male Wistar rats were pair-fed for 4 wk either a standard chow diet or one of three different LC-HFDs, which only differed in the relative abundance of fat and protein (percentages of fat/protein in dry matter: LC-75/10; LC-65/20; LC-55/30). We subsequently measured body composition by nuclear magnetic resonance (NMR), analyzed blood chemistry and urine acetone content, evaluated gene expression changes of key ketogenic and gluconeogenic genes, and measured energy expenditure (EE) and locomotor activity (LA) during the first 4 days and after 3 wk on the respective diets. Compared with chow, rats fed with LC-75/10, LC-65/20, and LC-55/30 gained significantly less body weight. Reductions in body weight were mainly due to lower lean body mass and paralleled by significantly increased fat mass. Levels of β-hydroxybutyate were significantly elevated feeding LC-75/10 and LC-65/20 but decreased in parallel to reductions in dietary fat. Acetone was about 16-fold higher with LC-75/10 only (P ketosis. LC-HFDs must be high in fat, but also low in protein contents to be clearly ketogenic. Independent of the macronutrient composition, LC-HFD-induced weight loss is not due to increased EE and LA.

Isocaloric intake of a high-fat diet modifies adiposity and lipid handling in a sex dependent manner in rats

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Lladó Isabel

2011-04-01

Full Text Available Abstract Background High-fat (HF diet feeding usually leads to hyperphagia and body weight gain, but macronutrient proportions in the diet can modulate energy intake and fat deposition. The mechanisms of fat accumulation and mobilization may differ significantly between depots, and gender can also influence these differences. Aim To investigate, in rats of both sexes, the effect of an isocaloric intake of a diet with an unbalanced proportion of macronutrients on fatty acid composition of visceral and subcutaneous adipose tissues and how this is influenced by both dietary fatty acids and levels of proteins involved in tissue lipid handling. Methods Eight-week-old Wistar rats of both sexes were fed a control diet (3% w/w fat or high-fat diet (30% w/w fat for 14 weeks. Fatty acid composition was analyzed by gas-chromatography and levels of LPL, HSL, α2-AR, β3-AR, PKA and CPT1 were determined by Western blot. Results The HF diet did not induce hyperphagia or body weight gain, but promoted an increase of adiposity index only in male rats. HF diet produced an increase of the proportion of MUFA and a decrease in that of PUFA in both adipose depots and in both sexes. The levels of proteins involved in the adrenergic control of the lipolytic pathway increased in the gonadal fat of HF females, whereas LPL levels increased in the inguinal fat of HF males and decreased in that of females. Conclusion Sexual dimorphism in adiposity index reflects a differential sex response to dietary fatty acid content and could be related to the levels of the proteins involved in tissue lipid management.

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

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Hong Sheng Cheng

2017-11-01

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

Voluntary running of defined distances reduces body adiposity and its associated inflammation in C57BL/6 mice fed a high-fat diet.

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Yan, Lin; Sundaram, Sneha; Nielsen, Forrest H

2017-11-01

This study investigated the effect of voluntary running of defined distances on body adiposity in male C57BL/6 mice fed a high-fat diet. Mice were assigned to 6 groups and fed a standard AIN93G diet (sedentary) or a modified high-fat AIN93G diet (sedentary; unrestricted running; or 75%, 50%, or 25% of unrestricted running) for 12 weeks. The average running distance was 8.3, 6.3, 4.2, and 2.1 km/day for the unrestricted, 75%, 50%, and 25% of unrestricted runners, respectively. Body adiposity was 46% higher in sedentary mice when fed the high-fat diet instead of the standard diet. Running decreased adiposity in mice fed the high-fat diet in a dose-dependent manner but with no significant difference between sedentary mice and those running 2.1 km/day. In sedentary mice, the high-fat instead of the standard diet increased insulin resistance, hepatic triacylglycerides, and adipose and plasma concentrations of leptin and monocyte chemotactic protein-1 (MCP-1). Running reduced these variables in a dose-dependent manner. Adipose adiponectin was lowest in sedentary mice fed the high-fat diet; running raised adiponectin in both adipose tissue and plasma. Running 8.3 and 6.3 km/day had the greatest, but similar, effects on the aforementioned variables. Running 2.1 km/day did not affect these variables except, when compared with sedentariness, it significantly decreased MCP-1. The findings showed that running 6.3 kg/day was optimal for reducing adiposity and associated inflammation that was increased in mice by feeding a high-fat diet. The findings suggest that voluntary running of defined distances may counteract the obesogenic effects of a high-fat diet.

Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding.

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More, Vijay R; Xu, Jialin; Shimpi, Prajakta C; Belgrave, Clyde; Luyendyk, James P; Yamamoto, Masayuki; Slitt, Angela L

2013-08-01

The nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway upregulates antioxidant and biotransformation enzyme expression to counter cellular oxidative stress. The contributions of Nrf2 to other cellular functions, such as lipid homeostasis, are emerging. This study was conducted to determine how enhanced Nrf2 activity influences the progression of metabolic syndrome with long-term high-fat diet (HFD) feeding. C57BL/6 and Keap1-knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight and white adipose tissue mass compared to C57BL/6 mice on HFD, along with increased inflammation and lipogenic gene expression. HFD feeding increased hepatic steatosis and inflammation to a greater extent in Keap1-KD mice compared to C57BL/6 mice, which was associated with increased liver Cd36, fatty acid-binding protein 4, and monocyte chemoattractant protein 1 mRNA expression, as well as increased acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1 protein expression. The HFD altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice, which was accompanied by downregulation of insulin receptor substrate 1 mRNA expression in skeletal muscle. Together, the results indicate that Keap1 knockdown, on treatment with HFD, increases certain markers of metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

High maysin corn silk extract reduces body weight and fat deposition in C57BL/6J mice fed high-fat diets.

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Lee, Eun Young; Kim, Sun Lim; Kang, Hyeon Jung; Kim, Myung Hwan; Ha, Ae Wha; Kim, Woo Kyoung

2016-12-01

The study was performed to investigate the effects and mechanisms of action of high maysin corn silk extract on body weight and fat deposition in experimental animals. A total of 30 male C57BL/6J mice, 4-weeks-old, were purchased and divided into three groups by weight using a randomized block design. The normal-fat (NF) group received 7% fat (diet weight basis), the high-fat (HF) group received 25% fat and 0.5% cholesterol, and the high-fat corn silk (HFCS) group received high-fat diet and high maysin corn silk extract at 100 mg/kg body weight through daily oral administration. Body weight and body fat were measured, and mRNA expression levels of proteins involved in adipocyte differentiation, fat accumulation, fat synthesis, lipolysis, and fat oxidation in adipose tissue and the liver were measured. After experimental diet intake for 8 weeks, body weight was significantly lower in the HFCS group compared to the HF group ( P corn silk extract inhibits expression of genes involved in adipocyte differentiation, fat accumulation, and fat synthesis as well as promotes expression of genes involved in lipolysis and fat oxidation, further inhibiting body fat accumulation and body weight elevation in experimental animals.

Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

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Cariou Bertrand

2013-01-01

Full Text Available Abstract Background PCSK9 (Proprotein Convertase Subtilisin Kexin type 9 is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2 and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. Methods We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D patients that are more prone to develop insulin resistance, including: i acute post-prandial hyperlipidemic challenge (n=10, ii 4 days of high-fat (HF or high-fat/high-protein (HFHP (n=10, iii 7 (HFruc1, n=16 or 6 (HFruc2, n=9 days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1. Findings HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05 in healthy volunteers and by 34% (p=0.001 in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p Conclusions Plasma PCSK9 concentrations vary

Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet.

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Hernandez, Teri L; Sutherland, Julie P; Wolfe, Pamela; Allian-Sauer, Marybeth; Capell, Warren H; Talley, Natalie D; Wyatt, Holly R; Foster, Gary D; Hill, James O; Eckel, Robert H

2010-03-01

Little is known about the comparative effect of weight-loss diets on metabolic profiles during dieting. The purpose of this study was to compare the effect of a low-carbohydrate diet (carbohydrate diet (55% of total energy intake) on fasting and hourly metabolic variables during active weight loss. Healthy, obese adults (n = 32; 22 women, 10 men) were randomly assigned to receive either a carbohydrate-restricted diet [High Fat; mean +/- SD body mass index (BMI; in kg/m(2)): 35.8 +/- 2.9] or a calorie-restricted, low-fat diet (High Carb; BMI: 36.7 +/- 4.6) for 6 wk. A 24-h in-patient feeding study was performed at baseline and after 6 wk. Glucose, insulin, free fatty acids (FFAs), and triglycerides were measured hourly during meals, at regimented times. Remnant lipoprotein cholesterol was measured every 4 h. Patients lost a similar amount of weight in both groups (P = 0.57). There was an absence of any diet treatment effect between groups on fasting triglycerides or on remnant lipoprotein cholesterol, which was the main outcome. Fasting insulin decreased (P = 0.03), and both fasting (P = 0.040) and 24-h FFAs (P Fat group. Twenty-four-hour insulin decreased (P loss was similar between diets, but only the high-fat diet increased LDL-cholesterol concentrations. This effect was related to the lack of suppression of both fasting and 24-h FFAs.

Ablation of PPP1R3G reduces glycogen deposition and mitigates high-fat diet induced obesity.

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Zhang, Yongxian; Gu, Jin; Wang, Lin; Zhao, Zilong; Pan, Yi; Chen, Yan

2017-01-05

Glycogen and triglyceride are two major forms of energy storage in the body and provide the fuel during different phases of food deprivation. However, how glycogen metabolism is linked to fat deposition in adipose tissue has not been clearly characterized. We generated a mouse model with whole-body deletion of PPP1R3G, a glycogen-targeting subunit of protein phosphatase-1 required for glycogen synthesis. Upon feeding with high-fat diet, the body weight and fat composition are significantly reduced in the PPP1R3G -/- mice compared to the wild type controls. The metabolic rate of the mice as measured by O 2 consumption and CO 2 production is accelerated by PPP1R3G deletion. The high-fat diet-induced liver steatosis is also slightly relieved by PPP1R3G deletion. The glycogen level in adipose tissue is reduced by PPP1R3G deletion. In 3T3L1 cells, overexpression of PPP1R3G leads to increases of both glycogen and triglyceride levels. In conclusion, our study indicates that glycogen is actively involved in fat accumulation in adipose tissue and obesity development upon high-fat diet. Our study also suggests that PPP1R3G is an important player that links glycogen metabolism to lipid metabolism in vivo. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of feeding hulled and hull-less barley with low- and high-forage diets on lactation performance, nutrient digestibility, and milk fatty acid composition of lactating dairy cows.

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Yang, Y; Ferreira, G; Teets, C L; Corl, B A; Thomason, W E; Griffey, C A

2018-04-01

The objective of this study was to evaluate lactation performance, nutrient digestibility, and milk fatty acid composition of high-producing dairy cows consuming diets containing hulled or hull-less barley as the grain source when feeding low-forage (LF) or high-forage (HF) diets. Eight primiparous (610 ± 40 kg of body weight and 72 ± 14 d in milk) and 16 multiparous (650 ± 58 kg of body weight and 58 ± 16 d in milk) Holstein cows were randomly assigned to 1 of 4 diets in a replicated 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments and 21-d periods. Cows were assigned to squares based on parity (1, 2, and ≥3) and days in milk. Diets were formulated to contain on a dry matter basis (1) 45% forage and hulled barley as the sole grain source, (2) 65% forage and hulled barley as the sole grain source, (3) 45% forage and hull-less barley as the sole grain source, and (4) 65% forage and hull-less barley as the sole grain source. Dry matter intake tended to be lower for the diet with 65% forage and hulled barley than for the rest of the diets (24.4 vs. 26.6 kg/d). Neither the type of barley nor the forage-to-concentrate ratio affected milk yield (41.7 kg/d). Barley type did not affect milk fat or protein concentrations. Feeding LF diets decreased milk fat concentration from 3.91% to 3.50%. This decrease was less than anticipated and resulted in a 7% decrease in milk fat yield relative to cows consuming HF diets (1.60 and 1.49 kg/d for HF and LF diets, respectively). Feeding LF diets increased the concentration of C18:1 trans-10 in milk fat, suggesting that feeding LF diets may have marginally altered rumen function. In conclusion, LF diets containing barley grains can marginally decrease milk fat concentration. Overall, and based on the conditions of this study, there is limited evidence to anticipate a dramatic or acute milk fat depression when feeding hull-less barley as the grain source in diets for high-producing dairy cows. Copyright

Impact of maternal high fat diet on hypothalamic transcriptome in neonatal Sprague Dawley rats.

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Sanna Barrand

Full Text Available Maternal consumption of a high fat diet during early development has been shown to impact the formation of hypothalamic neurocircuitry, thereby contributing to imbalances in appetite and energy homeostasis and increasing the risk of obesity in subsequent generations. Early in postnatal life, the neuronal projections responsible for energy homeostasis develop in response to appetite-related peptides such as leptin. To date, no study characterises the genome-wide transcriptional changes that occur in response to exposure to high fat diet during this critical window. We explored the effects of maternal high fat diet consumption on hypothalamic gene expression in Sprague Dawley rat offspring at postnatal day 10. RNA-sequencing enabled discovery of differentially expressed genes between offspring of dams fed a high fat diet and offspring of control diet fed dams. Female high fat diet offspring displayed altered expression of 86 genes (adjusted P-value<0.05, including genes coding for proteins of the extra cellular matrix, particularly Collagen 1a1 (Col1a1, Col1a2, Col3a1, and the imprinted Insulin-like growth factor 2 (Igf2 gene. Male high fat diet offspring showed significant changes in collagen genes (Col1a1 and Col3a1 and significant upregulation of two genes involved in regulation of dopamine availability in the brain, tyrosine hydroxylase (Th and dopamine reuptake transporter Slc6a3 (also known as Dat1. Transcriptional changes were accompanied by increased body weight, body fat and body length in the high fat diet offspring, as well as altered blood glucose and plasma leptin. Transcriptional changes identified in the hypothalamus of offspring of high fat diet mothers could alter neuronal projection formation during early development leading to abnormalities in the neuronal circuitry controlling appetite in later life, hence priming offspring to the development of obesity.

Hearts from mice fed a non-obesogenic high-fat diet exhibit changes in their oxidative state, calcium and mitochondria in parallel with increased susceptibility to reperfusion injury.

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Littlejohns, Ben; Pasdois, Philippe; Duggan, Simon; Bond, Andrew R; Heesom, Kate; Jackson, Christopher L; Angelini, Gianni D; Halestrap, Andrew P; Suleiman, M-Saadeh

2014-01-01

High-fat diet with obesity-associated co-morbidities triggers cardiac remodeling and renders the heart more vulnerable to ischemia/reperfusion injury. However, the effect of high-fat diet without obesity and associated co-morbidities is presently unknown. To characterize a non-obese mouse model of high-fat diet, assess the vulnerability of hearts to reperfusion injury and to investigate cardiac cellular remodeling in relation to the mechanism(s) underlying reperfusion injury. Feeding C57BL/6J male mice high-fat diet for 20 weeks did not induce obesity, diabetes, cardiac hypertrophy, cardiac dysfunction, atherosclerosis or cardiac apoptosis. However, isolated perfused hearts from mice fed high-fat diet were more vulnerable to reperfusion injury than those from mice fed normal diet. In isolated cardiomyocytes, high-fat diet was associated with higher diastolic intracellular Ca2+ concentration and greater damage to isolated cardiomyocytes following simulated ischemia/reperfusion. High-fat diet was also associated with changes in mitochondrial morphology and expression of some related proteins but not mitochondrial respiration or reactive oxygen species turnover rates. Proteomics, western blot and high-performance liquid chromatography techniques revealed that high-fat diet led to less cardiac oxidative stress, higher catalase expression and significant changes in expression of putative components of the mitochondrial permeability transition pore (mPTP). Inhibition of the mPTP conferred relatively more cardio-protection in the high-fat fed mice compared to normal diet. This study shows for the first time that high-fat diet, independent of obesity-induced co-morbidities, triggers changes in cardiac oxidative state, calcium handling and mitochondria which are likely to be responsible for increased vulnerability to cardiac insults.

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

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Brittany V Martin-Murphy

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

A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults.

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von Frankenberg, Anize D; Marina, Anna; Song, Xiaoling; Callahan, Holly S; Kratz, Mario; Utzschneider, Kristina M

2017-02-01

We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10: 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10: 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography. The rate of glucose disposal (Rd) during low- and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low: LFD: 0.12 ± 0.11 vs. HFD: -0.37 ± 0.15 mmol/min, mean ± SE, p vs. HFD: -0.71 ± 0.26 mmol/min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p fat. The LFD led to an increase in VLDL palmitic (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) were strongly associated with changes in insulin sensitivity on both diets (LFD: r = -0.77; p fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes. CLINICALTRIALS. NCT00930371.

Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

International Nuclear Information System (INIS)

Tao, Y.; Zhang, H.; Gao, B.; Guo, J.; Hu, Y.; Su, Z.

2011-01-01

Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC) has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs) on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800?nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD) activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia

Diets with high-fat cheese, high-fat meat, or carbohydrate on cardiovascular risk markers in overweight postmenopausal women

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Thorning, Tanja Kongerslev; Raziani, Farinaz; Bendsen, Nathalie Tommerup

2015-01-01

BACKGROUND: Heart associations recommend limited intake of saturated fat. However, effects of saturated fat on low-density lipoprotein (LDL)-cholesterol concentrations and cardiovascular disease risk might depend on nutrients and specific saturated fatty acids (SFAs) in food. OBJECTIVE: We explored...... the effects of cheese and meat as sources of SFAs or isocaloric replacement with carbohydrates on blood lipids, lipoproteins, and fecal excretion of fat and bile acids. DESIGN: The study was a randomized, crossover, open-label intervention in 14 overweight postmenopausal women. Three full-diet periods of 2-wk...... duration were provided separated by 2-wk washout periods. The isocaloric diets were as follows: 1) a high-cheese (96-120-g) intervention [i.e., intervention containing cheese (CHEESE)], 2) a macronutrient-matched nondairy, high-meat control [i.e., nondairy control with a high content of high-fat processed...

Maternal High Fat Feeding Does Not Have Long-Lasting Effects on Body Composition and Bone Health in Female and Male Wistar Rat Offspring at Young Adulthood

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Paula M. Miotto

2013-12-01

Full Text Available High fat diets adversely affect body composition, bone mineral and strength, and alter bone fatty acid composition. It is unclear if maternal high fat (HF feeding permanently alters offspring body composition and bone health. Female rats were fed control (CON or HF diet for 10 weeks, bred, and continued their diets throughout pregnancy and lactation. Male and female offspring were studied at weaning and 3 months, following consumption of CON diet. At weaning, but not 3 months of age, male and female offspring from dams fed HF diet had lower lean mass and higher fat and bone mass, and higher femur bone mineral density (females only than offspring of dams fed CON diet. Male and female offspring femurs from dams fed HF diet had higher monounsaturates and lower n6 polyunsaturates at weaning than offspring from dams fed CON diet, where females from dams fed HF diet had higher saturates and lower n6 polyunsaturates at 3 months of age. There were no differences in strength of femurs or lumbar vertebrae at 3 months of age in either male or female offspring. In conclusion, maternal HF feeding did not permanently affect body composition and bone health at young adulthood in offspring.

Moderate high fat diet increases sucrose self-administration in young rats.

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Figlewicz, Dianne P; Jay, Jennifer L; Acheson, Molly A; Magrisso, Irwin J; West, Constance H; Zavosh, Aryana; Benoit, Stephen C; Davis, Jon F

2013-02-01

We have previously reported that a moderately high fat diet increases motivation for sucrose in adult rats. In this study, we tested the motivational, neurochemical, and metabolic effects of the high fat diet in male rats transitioning through puberty, during 5-8 weeks of age. We observed that the high fat diet increased motivated responding for sucrose, which was independent of either metabolic changes or changes in catecholamine neurotransmitter metabolites in the nucleus accumbens. However, AGRP mRNA levels in the hypothalamus were significantly elevated. We demonstrated that increased activation of AGRP neurons is associated with motivated behavior, and that exogenous (third cerebroventricular) AGRP administration resulted in significantly increased motivation for sucrose. These observations suggest that increased expression and activity of AGRP in the medial hypothalamus may underlie the increased responding for sucrose caused by the high fat diet intervention. Finally, we compared motivation for sucrose in pubertal vs. adult rats and observed increased motivation for sucrose in the pubertal rats, which is consistent with previous reports that young animals and humans have an increased preference for sweet taste, compared with adults. Together, our studies suggest that background diet plays a strong modulatory role in motivation for sweet taste in adolescent animals. Published by Elsevier Ltd.

Effect of Morinda citrifolia (Noni) Fruit Juice on High Fat Diet Induced Dyslipidemia in Rats.

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Shoeb, Ahsan; Alwar, M C; Shenoy, Preethi J; Gokul, P

2016-04-01

The medicinal value of Morinda citrifolia L. (commonly known as Noni) has been explored in ancient folk remedies with a wide range of therapeutic utility, including antibacterial, antiviral, antifungal, antitumour, analgesic, hypotensive, anti-inflammatory and immune enhancing effects. The present study was designed to evaluate the effects of Noni fruit juice on serum lipid profile in high fat diet induced murine model of dyslipidemia. Hyperlipidemia was induced by feeding a cholesterol rich high fat diet for 45 days in wistar albino rats of either sex (n=8). Noni fruit juice administered at 50mg/kg/day and 100mg/kg/day, per oral, was compared with the standard drug Atorvastatin (10mg/kg/day, oral) fed for the latter 30 days. The blood samples were then sent for complete blood lipid profile, after 30 days of treatment. The data presented as mean ± SEM was analyzed using one-way ANOVA followed by Tukey's post-hoc test. The p juice treated group showed a significant decrease in the total cholesterol, triglycerides and very low density lipoprotein - Cholesterol at both the doses when compared to the disease control (pjuice at the 50mg/kg dose employed, failed to show a statistical significance when compared to atorvastatin. The present study provides evidence for the hypolipidemic activity of Noni fruit juice in high fat diet induced hyperlipidemia in rats.

The effect of feeding high fat diet to beef cattle on manure composition and gaseous emission from a feedlot pen surface

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Dhan Prasad Gautam

2016-06-01

Full Text Available Abstract Background Dietary manipulation is a common practice to mitigate gaseous emission from livestock production facilities, and the variation of fat level in the diet has shown great influence on ruminal volatile fatty acids (VFA and enteric methane generation. The changes in dietary fat levels influence rumen chemistry that could modify manure nutrient composition along with odor and gaseous emissions from manure management facilities. Methods A field experiment was carried out on beef cattle feedlots to investigate the effect of four levels of dietary fat concentrations (3 to 5.5 % on the manure composition and gaseous emissions (methane-CH4, nitrous oxide-N2O, carbon dioxide-CO2 and hydrogen sulfide-H2S from the feedlot pen surface. The experiment was carried out over a 5-month period from June to October during North Dakota’s summer-fall climatic condition. Air and manure sampling was conducted five times at a 20–30 day intervals. Results Overall, this research indicated that fat levels in diet have no or little effect on the nutrient composition of manure and gaseous emission from the pens with cattle fed with different diet. Though significant variation of gaseous emission and manure composition were observed between different sampling periods, no effect of high fat diet was observed on manure composition and gaseous emission. Conclusions It can be concluded that addition of fat to animal diet may not have any impact on gaseous emission and manure compositions.

The effect of feeding high fat diet to beef cattle on manure composition and gaseous emission from a feedlot pen surface.

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Gautam, Dhan Prasad; Rahman, Shafiqur; Borhan, Md Saidul; Engel, Chanda

2016-01-01

Dietary manipulation is a common practice to mitigate gaseous emission from livestock production facilities, and the variation of fat level in the diet has shown great influence on ruminal volatile fatty acids (VFA) and enteric methane generation. The changes in dietary fat levels influence rumen chemistry that could modify manure nutrient composition along with odor and gaseous emissions from manure management facilities. A field experiment was carried out on beef cattle feedlots to investigate the effect of four levels of dietary fat concentrations (3 to 5.5 %) on the manure composition and gaseous emissions (methane-CH4, nitrous oxide-N2O, carbon dioxide-CO2 and hydrogen sulfide-H2S) from the feedlot pen surface. The experiment was carried out over a 5-month period from June to October during North Dakota's summer-fall climatic condition. Air and manure sampling was conducted five times at a 20-30 day intervals. Overall, this research indicated that fat levels in diet have no or little effect on the nutrient composition of manure and gaseous emission from the pens with cattle fed with different diet. Though significant variation of gaseous emission and manure composition were observed between different sampling periods, no effect of high fat diet was observed on manure composition and gaseous emission. It can be concluded that addition of fat to animal diet may not have any impact on gaseous emission and manure compositions.

Acute vs chronic exposure to high fat diet leads to distinct regulation of PKA.

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London, Edra; Nesterova, Maria; Stratakis, Constantine A

2017-07-01

The cAMP-dependent protein kinase (PKA) is an essential regulator of lipid and glucose metabolism that plays a critical role in energy homeostasis. The impact of diet on PKA signaling has not been defined, although perturbations in individual PKA subunits are associated with changes in adiposity, physical activity and energy intake in mice and humans. We hypothesized that a high fat diet (HFD) would elicit peripheral and central alterations in the PKA system that would differ depending on length of exposure to HFD; these differences could protect against or promote diet-induced obesity (DIO). 12-week-old C57Bl/6J mice were randomly assigned to a regular diet or HFD and weighed weekly throughout the feeding studies (4 days, 14 weeks; respectively), and during killing. PKA activity and subunit expression were measured in liver, gonadal adipose tissue (AT) and brain. Acute HFD-feeding suppressed basal hepatic PKA activity. In contrast, hepatic and hypothalamic PKA activities were significantly increased after chronic HFD-feeding. Changes in AT were more subtle, and overall, altered PKA regulation in response to chronic HFD exposure was more profound in female mice. The suppression of hepatic PKA activity after 4 day HFD-feeding was indicative of a protective peripheral effect against obesity in the context of overnutrition. In response to chronic HFD-feeding, and with the development of DIO, dysregulated hepatic and hypothalamic PKA signaling was a signature of obesity that is likely to promote further metabolic dysfunction in mice. © 2017 Society for Endocrinology.

Voluntary exercise contributed to an amelioration of abnormal feeding behavior, locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats.

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Mifune, Hiroharu; Tajiri, Yuji; Nishi, Yoshihiro; Hara, Kento; Iwata, Shimpei; Tokubuchi, Ichiro; Mitsuzono, Ryouichi; Yamada, Kentaro; Kojima, Masayasu

2015-09-01

In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague-Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle.

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Jingbo Liu

Full Text Available It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR increases the susceptibility of offspring to high-fat (HF diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW, and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA, and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH and glucose-6-phosphate dehydrogenase (G6PD. These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction.

Intrauterine Growth Retardation Increases the Susceptibility of Pigs to High-Fat Diet-Induced Mitochondrial Dysfunction in Skeletal Muscle

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Liu, Jingbo; Chen, Daiwen; Yao, Ying; Yu, Bing; Mao, Xiangbing; He, Jun; Huang, Zhiqing; Zheng, Ping

2012-01-01

It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. PMID:22523560

Gender-specific reduction of hepatic Mrp2 expression by high-fat diet protects female mice from ANIT toxicity

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Kong, Bo; Csanaky, Iván L.; Aleksunes, Lauren M.; Patni, Meghan; Chen, Qi; Ma, Xiaochao; Jaeschke, Hartmut; Weir, Scott; Broward, Melinda; Klaassen, Curtis D.; Guo, Grace L.

2012-01-01

Emerging evidence suggests that feeding a high-fat diet (HFD) to rodents affects the expression of genes involved in drug transport. However, gender-specific effects of HFD on drug transport are not known. The multidrug resistance-associated protein 2 (Mrp2, Abcc2) is a transporter highly expressed in the hepatocyte canalicular membrane and is important for biliary excretion of glutathione-conjugated chemicals. The current study showed that hepatic Mrp2 expression was reduced by HFD feeding only in female, but not male, C57BL/6J mice. In order to determine whether down-regulation of Mrp2 in female mice altered chemical disposition and toxicity, the biliary excretion and hepatotoxicity of the Mrp2 substrate, α-naphthylisothiocyanate (ANIT), were assessed in male and female mice fed control diet or HFD for 4 weeks. ANIT-induced biliary injury is a commonly used model of experimental cholestasis and has been shown to be dependent upon Mrp2-mediated efflux of an ANIT glutathione conjugate that selectively injures biliary epithelial cells. Interestingly, HFD feeding significantly reduced early-phase biliary ANIT excretion in female mice and largely protected against ANIT-induced liver injury. In summary, the current study showed that, at least in mice, HFD feeding can differentially regulate Mrp2 expression and function and depending upon the chemical exposure may enhance or reduce susceptibility to toxicity. Taken together, these data provide a novel interaction between diet and gender in regulating hepatobiliary excretion and susceptibility to injury. -- Highlights: ► High-fat diet decreases hepatic Mrp2 expression only in female but not in male mice. ► HFD significantly reduces early-phase biliary ANIT excretion in female mice. ► HFD protects female mice against ANIT-induced liver injury.

A maternal high-protein diet predisposes female offspring to increased fat mass in adulthood whereas a prebiotic fibre diet decreases fat mass in rats.

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Hallam, Megan C; Reimer, Raylene A

2013-11-14

The negative effects of malnourishment in utero have been widely explored; the effects of increased maternal macronutrient intake are not known in relation to high fibre, and have been inconclusive with regard to high protein. In the present study, virgin Wistar dams were fed either a control (C), high-protein (40 %, w/w; HP) or high-prebiotic fibre (21·6 %, w/w; HF) diet throughout pregnancy and lactation. Pups consumed the C diet from 3 to 14·5 weeks of age, and then switched to a high-fat/sucrose diet for 8 weeks. A dual-energy X-ray absorptiometry scan and an oral glucose tolerance test were performed and plasma satiety hormones measured. The final body weight and the percentage of body fat were significantly affected by the interaction between maternal diet and offspring sex: weight and fat mass were higher in the female offspring of the HP v. HF dams. No differences in body weight or fat mass were seen in the male offspring. There was a significant sex effect for fasting and total AUC for ghrelin and fasting GIP, with females having higher levels than males. Liver TAG content and plasma NEFA were lower in the offspring of high-prebiotic fibre dams (HF1) than in those of high-protein dams (HP1) and control dams (C1). Intestinal expression of GLUT2 was decreased in HF1 and HP1 v. C1. The maternal HP and HF diets had lasting effects on body fat and hepatic TAG accumulation in the offspring, particularly in females. Whereas the HP diet predisposes to an obese phenotype, the maternal HF diet appears to reduce the susceptibility to obesity following a high-energy diet challenge in adulthood.

Dietary Shiitake Mushroom (Lentinus edodes Prevents Fat Deposition and Lowers Triglyceride in Rats Fed a High-Fat Diet

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D. Handayani

2011-01-01

Full Text Available High-fat diet (HFD induces obesity. This study examined the effects of Shiitake mushroom on the prevention of alterations of plasma lipid profiles, fat deposition, energy efficiency, and body fat index induced by HFD. Rats were given a low, medium, and high (7, 20, 60 g/kg = LD-M, MD-M, HD-M Shiitake mushroom powder in their high-fat (50% in kcal diets for 6 weeks. The results showed that the rats on the HD-M diet had the lowest body weight gain compared to MD-M and LD-M groups (P<0.05. The total fat deposition was significantly lower (−35%, P<0.05 in rats fed an HD-M diet than that of HFD group. Interestingly, plasma triacylglycerol (TAG level was significantly lower (−55%, P<0.05 in rats on HD-M than HFD. This study also revealed the existence of negative correlations between the amount of Shiitake mushroom supplementation and body weight gain, plasma TAG, and total fat masses.

Carbohydrate- vs fat-controlled diet effect on weight loss and coronary artery disease risk: a pilot feeding study.

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Mueller, Charles; Masri, Basem; Hogg, Jeannette; Mastrogiacomo, Maddalena; Chiu, Ya-Lin

2010-10-01

This pilot study compared weight loss and serum indicators of coronary artery disease (CAD) risk between 2 weight loss (energy-deficit) diets, one controlled for carbohydrate as a percentage of total calories and the other controlled for fat as percentage of total calories. Participants were randomized to 1 of 2 diets and fed on an outpatient basis for 70 days, after which they followed their diets using their own resources for an additional 70 days. Energy deficit for the diets was determined by indirect calorimetry with a 500- to 750-calorie per day adjustment. Weight and CAD risk indicators and serum lipid and C-reactive protein levels were measured at baseline, day 70, and day 140. The study was completed by 16 of 20 participants who were able to comply with the feeding portion of the study as well as with follow-up appointments during the second (self-management) period of the study. Participants lost weight in both diet groups (24.4 lbs, carbohydrate controlled; 18.5 lbs, fat controlled), and serum CAD risk factors decreased in both groups. There were no significant differences in CAD risk factors between diet groups, although there was a trend toward lighter low-density lipoprotein (LDL) size in the carbohydrate-controlled group. During the self-management portion of the study, weight loss stalled or regained from loss during the previous feeding period. The results, although underpowered, are consistent with recent studies in which macronutrient ratio of total calories in diet did not affect degree of weight loss and in which carbohydrate-controlled diets produced a predominance of lighter LDLs.

High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

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Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

2013-01-01

Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

Impairment of fat oxidation under high- vs. low-glycemic index diet occurs before the development of an obese phenotype.

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Isken, F; Klaus, S; Petzke, K J; Loddenkemper, C; Pfeiffer, A F H; Weickert, M O

2010-02-01

Exposure to high vs. low glycemic index (GI) diets increases fat mass and insulin resistance in obesity-prone C57BL/6J mice. However, the longer-term effects and potentially involved mechanisms are largely unknown. We exposed four groups of male C57BL/6J mice (n = 10 per group) to long-term (20 wk) or short-term (6 wk) isoenergetic and macronutrient matched diets only differing in starch type and as such GI. Body composition, liver fat, molecular factors of lipid metabolism, and markers of insulin sensitivity and metabolic flexibility were investigated in all four groups of mice. Mice fed the high GI diet showed a rapid-onset (from week 5) marked increase in body fat mass and liver fat, a gene expression profile in liver consistent with elevated lipogenesis, and, after long-term exposure, significantly reduced glucose clearance following a glucose load. The long-term high-GI diet also led to a delayed switch to both carbohydrate and fat oxidation in the postprandial state, indicating reduced metabolic flexibility. In contrast, no difference in carbohydrate oxidation was observed after short-term high- vs. low-GI exposure. However, fatty acid oxidation was significantly blunted as early as 3 wk after beginning of the high-GI intervention, at a time where most measured phenotypic markers including body fat mass were comparable between groups. Thus long-term high-GI feeding resulted in an obese, insulin-resistant, and metabolically inflexible phenotype in obesity-prone C57BL/6J mice. Early onset and significantly impaired fatty acid oxidation preceded these changes, thereby indicating a potentially causal involvement.

Role of glycogen-lowering exercise in the change of fat oxidation in response to a high-fat diet.

NARCIS (Netherlands)

Schrauwen, P.; van Marken Lichtenbelt, W.D.; Saris, W.H.M.; Westerterp, K.R.

1997-01-01

Department of Human Biology, Maastricht University, The Netherlands. One of the candidate factors for determining the increase of fat oxidation after a switch from a reduced-fat diet to a high-fat diet is the size of the glycogen storage. Therefore, we studied the effect of low glycogen stores on

Impact of a High-Fat or High-Fiber Diet on Intestinal Microbiota and Metabolic Markers in a Pig Model

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Sonja N. Heinritz

2016-05-01

Full Text Available To further elaborate interactions between nutrition, gut microbiota and host health, an animal model to simulate changes in microbial composition and activity due to dietary changes similar to those in humans is needed. Therefore, the impact of two different diets on cecal and colonic microbial gene copies and metabolic activity, organ development and biochemical parameters in blood serum was investigated using a pig model. Four pigs were either fed a low-fat/high-fiber (LF, or a high-fat/low-fiber (HF diet for seven weeks, with both diets being isocaloric. A hypotrophic effect of the HF diet on digestive organs could be observed compared to the LF diet (p < 0.05. Higher gene copy numbers of Bacteroides (p < 0.05 and Enterobacteriaceae (p < 0.001 were present in intestinal contents of HF pigs, bifidobacteria were more abundant in LF pigs (p < 0.05. Concentrations of acetate and butyrate were higher in LF pigs (p < 0.05. Glucose was higher in HF pigs, while glutamic pyruvic transaminase (GPT showed higher concentrations upon feeding the LF diet (p < 0.001. However, C-reactive protein (CRP decreased with time in LF pigs (p < 0.05. In part, these findings correspond to those in humans, and are in support of the concept of using the pig as human model.

Effects of preoperative exposure to a high-fat versus a low-fat diet on ingestive behavior after gastric bypass surgery in rats.

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Seyfried, Florian; Miras, Alexander D; Bueter, Marco; Prechtl, Christina G; Spector, Alan C; le Roux, Carel W

2013-11-01

The consumption of high fat and sugar diets is decreased after gastric bypass surgery (GB). The mechanisms remain unclear, with tests of motivated behavior toward fat and sugar producing conflicting results in a rat model. These discrepancies may be due to differences in presurgical maintenance diets. The authors used their GB rat model to determine whether the fat content of preoperative maintenance diets affects weight loss, calorie intake, and macronutrient selection after surgery. Male Wistar rats were either low-fat diet fed (LFDF) with normal chow or high-fat diet fed (HFDF) before randomization to GB or sham surgery. In food preference test 1, the animals were offered the choice of a vegetable drink (V8) or a high-calorie liquid (Ensure), and in food preference test 2, they could choose normal chow or a solid high-fat diet. The GB groups did not differ significantly in terms of body weight loss or caloric intake. In food preference test 1, both groups responded similarly by reducing their preference for Ensure and increasing their preference for V8. In food preference test 2, the HFDF-GB rats reduced their preference for a solid high-fat diet gradually compared with the immediate reduction observed in the LFDF-GB rats. The consumption of presurgical maintenance diets with different fat contents did not affect postoperative weight loss outcomes. Both the LFDF-GB and HFDF-GB rats exhibited behaviors consistent with the possible expression of a conditioned taste aversion to a high-fat stimulus. These results suggest that for some physiologic parameters, low-fat-induced obesity models can be used for the study of changes after GB and have relevance to many obese humans who consume high-calorie but low-fat diets.

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

KAUST Repository

Diaz Rua, Ruben; Van Schothorst, E. M.; Keijer, J.; Palou, A.; Oliver, P.

2016-01-01

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

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

KAUST Repository

Diaz Rua, Ruben

2016-03-22

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

Programming Effects of Prenatal Glucocorticoid Exposure with a Postnatal High-Fat Diet in Diabetes Mellitus

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Jiunn-Ming Sheen

2016-04-01

Full Text Available Increasing evidence has shown that many chronic diseases originate from early life, even before birth, through what are termed as fetal programming effects. Glucocorticoids are frequently used prenatally to accelerate the maturation of the lungs of premature infants. High-fat diets are associated with insulin resistance, but the effects of prenatal glucocorticoid exposure plus a postnatal high-fat diet in diabetes mellitus remain unclear. We administered pregnant Sprague-Dawley rats’ intraperitoneal dexamethasone (0.1 mg/kg body weight or vehicle at gestational days 14–20. Male offspring were administered a normal or high-fat diet starting from weaning. We assessed the effects of prenatal steroid exposure plus postnatal high-fat diet on the liver, pancreas, muscle and fat at postnatal day 120. At 15 and 30 min, sugar levels were higher in the dexamethasone plus high-fat diet (DHF group than the vehicle plus high-fat diet (VHF group in the intraperitoneal glucose tolerance test (IPGTT. Serum insulin levels at 15, 30 and 60 min were significantly higher in the VHF group than in the vehicle and normal diet group. Liver insulin receptor and adenosine monophosphate-activated protein kinase mRNA expressions and protein levels were lower in the DHF group. Insulin receptor and insulin receptor substrate-1 mRNA expressions were lower in the epididymal adipose tissue in the VHF and DHF groups. “Programming” of liver or epididymal adipose tissue resulted from prenatal events. Prenatal steroid exposure worsened insulin resistance in animals fed a high-fat diet.

Programming Effects of Prenatal Glucocorticoid Exposure with a Postnatal High-Fat Diet in Diabetes Mellitus.

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Sheen, Jiunn-Ming; Hsieh, Chih-Sung; Tain, You-Lin; Li, Shih-Wen; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Miao-Meng; Chen, Yu-Chieh; Huang, Li-Tung

2016-04-08

Increasing evidence has shown that many chronic diseases originate from early life, even before birth, through what are termed as fetal programming effects. Glucocorticoids are frequently used prenatally to accelerate the maturation of the lungs of premature infants. High-fat diets are associated with insulin resistance, but the effects of prenatal glucocorticoid exposure plus a postnatal high-fat diet in diabetes mellitus remain unclear. We administered pregnant Sprague-Dawley rats' intraperitoneal dexamethasone (0.1 mg/kg body weight) or vehicle at gestational days 14-20. Male offspring were administered a normal or high-fat diet starting from weaning. We assessed the effects of prenatal steroid exposure plus postnatal high-fat diet on the liver, pancreas, muscle and fat at postnatal day 120. At 15 and 30 min, sugar levels were higher in the dexamethasone plus high-fat diet (DHF) group than the vehicle plus high-fat diet (VHF) group in the intraperitoneal glucose tolerance test (IPGTT). Serum insulin levels at 15, 30 and 60 min were significantly higher in the VHF group than in the vehicle and normal diet group. Liver insulin receptor and adenosine monophosphate-activated protein kinase mRNA expressions and protein levels were lower in the DHF group. Insulin receptor and insulin receptor substrate-1 mRNA expressions were lower in the epididymal adipose tissue in the VHF and DHF groups. "Programming" of liver or epididymal adipose tissue resulted from prenatal events. Prenatal steroid exposure worsened insulin resistance in animals fed a high-fat diet.

High fat feeding affects the number of GPR120 cells and enteroendocrine cells in the mouse stomach

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Patricia eWidmayer

2015-02-01

Full Text Available Long-term intake of dietary fat is supposed to be associated with adaptive reactions of the organism and it is assumptive that this is particularly true for fat responsive epithelial cells in the mucosa of the gastrointestinal tract. Recent studies suggest that epithelial cells expressing the receptor for medium and long chain fatty acids, GPR120 (FFAR4, may operate as fat sensors. Changes in expression level and/or cell density are supposed to be accompanied with a consumption of high fat (HF diet. To assess whether feeding a HF diet might impact on the expression of fatty acid receptors or the number of lipid sensing cells as well as enteroendocrine cell populations, gastric tissue samples of non-obese and obese mice were compared using a real time PCR and immunohistochemical approach. In this study, we have identified GPR120 cells in the corpus region of the mouse stomach which appeared to be brush cells. Monitoring the effect of HF diet on the expression of GPR120 revealed that after 3 weeks and 6 months the level of mRNA for GPR120 in the tissue was significantly increased which coincided with and probably reflected a significant increase in the number of GPR120 positive cells in the corpus region; in contrast, within the antrum region, the number of GPR120 cells decreased. Furthermore, dietary fat intake also led to changes in the number of enteroendocrine cells producing either ghrelin or gastrin. After 3 weeks and even more pronounced after 6 months the number of ghrelin cells and gastrin cells was significantly increased. These results imply that a HF diet leads to significant changes in the cellular repertoire of the stomach mucosa. Whether these changes are a consequence of the direct exposure to high fat in the luminal content or a physiological response to the high level of fat in the body remains elusive.

Effects of high-fat diet and fructose-rich diet on obesity, dyslipidemia and hyperglycemia in the WBN/Kob-Leprfa rat, a new model of type 2 diabetes mellitus.

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Namekawa, Junichi; Takagi, Yoshiichi; Wakabayashi, Kaoru; Nakamura, Yuki; Watanabe, Ayaka; Nagakubo, Dai; Shirai, Mitsuyuki; Asai, Fumitoshi

2017-06-10

Obesity and type 2 diabetes mellitus (T2DM) are occurring at epidemic-like rates, and these epidemics appear to have emerged largely from changes in daily diet. In the present study, we compared effects of high-fat diet (HFD) and fructose-rich diet (FRD) in WBN/Kob-Lepr fa (WBKDF) rats that spontaneously develop obesity, dyslipidemia and T2DM. After a 4-week feeding of each diet, WBKDF-HFD and WBKDF-FRD rats exhibited aggravated obesity and dyslipidemia compared with WBKDF rats fed standard diet (STD). In contrast, hyperglycemia developed in WBKDF-STD rats was significantly inhibited in WBKDF-FRD rats, but not in WBKDF-HFD rats. The present study demonstrated that the 4-week feeding of HFD and FRD caused diet-induced obesity with a distinct phenotype in the glucose metabolism in WBKDF rats.

High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling.

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Gómez-Ruiz, Ana; Milagro, Fermín I; Campión, Javier; Martínez, J Alfredo; de Miguel, Carlos

2011-04-13

The effect of food intake on caveolin expression in relation to insulin signalling was studied in skeletal muscle and adipocytes from retroperitoneal (RP) and subcutaneous (SC) adipose tissue, comparing fasted (F) to not fasted (NF) rats that had been fed a control or high-fat (HF) diet for 72 days. Serum glucose was analysed enzymatically and insulin and leptin by ELISA. Caveolins and insulin signalling intermediaries (IR, IRS-1 and 2 and GLUT4) were determined by RT-PCR and western blotting. Caveolin and IR phosphorylation was measured by immunoprecipitation. Data were analysed with Mann-Whitney U test. High-fat fed animals showed metabolic alterations and developed obesity and insulin resistance. In skeletal muscle, food intake (NF) induced activation of IR and increased expression of IRS-2 in control animals with normal metabolic response. HF animals became overweight, hyperglycaemic, hyperinsulinemic, hyperleptinemic and showed insulin resistance. In skeletal muscle of these animals, food intake (NF) also induced IRS-2 expression together with IR, although this was not active. Caveolin 3 expression in this tissue was increased by food intake (NF) in animals fed either diet. In RP adipocytes of control animals, food intake (NF) decreased IR and IRS-2 expression but increased that of GLUT4. A similar but less intense response was found in SC adipocytes. Food intake (NF) did not change caveolin expression in RP adipocytes with either diet, but in SC adipocytes of HF animals a reduction was observed. Food intake (NF) decreased caveolin-1 phosphorylation in RP but increased it in SC adipocytes of control animals, whereas it increased caveolin-2 phosphorylation in both types of adipocytes independently of the diet. Animals fed a control-diet show a normal response to food intake (NF), with activation of the insulin signalling pathway but without appreciable changes in caveolin expression, except a small increase of caveolin-3 in muscle. Animals fed a high-fat diet

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

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

2018-01-01

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

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

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

2018-01-01

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

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

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

2012-09-10

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

Effect of bacterial or porcine lipase with low- or high-fat diets on nutrient absorption in pancreatic-insufficient dogs.

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Suzuki, A; Mizumoto, A; Rerknimitr, R; Sarr, M G; DiMango, E P

1999-02-01

Treatment of human exocrine pancreatic insufficiency is suboptimal. This study assessed the effects of bacterial lipase, porcine lipase, and diets on carbohydrate, fat, and protein absorption in pancreatic-insufficient dogs. Dogs were given bacterial or porcine lipase and 3 diets: a 48% carbohydrate, 27% fat, and 25% protein standard diet; a high-carbohydrate, low-fat, and low-protein diet; or a low-carbohydrate, high-fat, and high-protein diet (66%/18%/16% and 21%/43%/36% calories). With the standard diet, coefficient of fat absorption increased dose-dependently with both lipases (P vs. low-fat and -protein diet). There were no interactions among carbohydrate, fat, and protein absorption. Correcting steatorrhea requires 75 times more porcine than bacterial lipase (18 vs. 240 mg). High-fat and high-protein diets optimize fat absorption with both enzymes. High-fat diets with bacterial or porcine lipase should be evaluated in humans with pancreatic steatorrhea.

Tissue Specific Expression Of Sprouty1 In Mice Protects Against High Fat Diet Induced Fat Accumulation, Bone Loss, And Metabolic Dysfunction

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Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J.; Liaw, Lucy

2012-01-01

We recently characterized Sprouty1 (Spry1), a growth factor signaling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue specific Spry1 expression in mice resulted in increased bone mass and reduced body fat while conditional knockout of Spry1 had the opposite effect with decreased bone and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high fat diet-induced obesity, bone loss, and associated lipid abnormalities and demonstrate that Spry1 has a long-term protective effect on mice fed a high caloric diet. We studied diet-induced obesity in mice with fatty acid binding promoter (aP2)-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1 null mice, high fat diet increased body fat by 40%, impaired glucose regulation, and led to liver steatosis. However, over-expression of Spry1 led to 35% lower body fat, reduced bone loss, and normal metabolic function compared to single transgenics. This protective phenotype was associated with decreased circulating insulin (70%) and leptin (54%) compared to controls on a high fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45%. We show that conditional Spry1 expression in adipose tissue protects against high fat diet-induced obesity and associated bone loss. PMID:22142492

Macrophage migration inhibitory factor (MIF) knockout preserves cardiac homeostasis through alleviating Akt-mediated myocardial autophagy suppression in high-fat diet-induced obesity.

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Xu, X; Ren, J

2015-03-01

Macrophage migration inhibitory factor (MIF) has a role in the development of obesity and diabetes. However, whether MIF has a role in fat diet-induced obesity and associated cardiac anomalies still remains unknown. The aim of this study was to examine the impact of MIF knockout on high-fat diet-induced obesity, obesity-associated cardiac anomalies and the underlying mechanisms involved with a focus on Akt-mediated autophagy. Adult male wild-type (WT) and MIF knockout (MIF(-/-)) mice were placed on 45% high-fat diet for 5 months. Oxygen consumption, CO2 production, respiratory exchange ratio, locomotor activity and heat generation were measured using energy calorimeter. Echocardiographic, cardiomyocyte mechanical and intracellular Ca2+ properties were assessed. Apoptosis was examined using terminal dUTP nick end labeling staining and western blot analysis. Akt signaling pathway and autophagy markers were evaluated. Cardiomyocytes isolated from WT and MIF(-/-) mice were treated with recombinant mouse MIF (rmMIF). High-fat diet feeding elicited increased body weight gain, insulin resistance and caloric disturbance in WT and MIF(-/-) mice. High-fat diet induced unfavorable geometric, contractile and histological changes in the heart, the effects of which were alleviated by MIF knockout. In addition, fat diet-induced cardiac anomalies were associated with Akt activation and autophagy suppression, which were nullified by MIF deficiency. In cardiomyocytes from WT mice, autophagy was inhibited by exogenous rmMIF through Akt activation. In addition, MIF knockout rescued palmitic acid-induced suppression of cardiomyocyte autophagy, the effect of which was nullified by rmMIF. These results indicate that MIF knockout preserved obesity-associated cardiac anomalies without affecting fat diet-induced obesity, probably through restoring myocardial autophagy in an Akt-dependent manner. Our findings provide new insights for the role of MIF in obesity and associated cardiac

Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats

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Yi Tao

2011-01-01

Full Text Available Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800 nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia.

The effects of losartan on memory performance and leptin resistance induced by obesity and high-fat diet in adult male rats.

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Sharieh Hosseini, Seyydeh Gohar; Khatamsaz, Saeed; Shariati, Mehrdad

2014-01-01

Leptin is a hormone secreted by adipose tissue and is involved not only in the regulation of feeding and energy expenditure, but also its role in memory enhancement has been demonstrated as well. The partial transfer of leptin across the blood-brain barrier in obese individuals causes leptin resistance and prevents leptin reaching brain. On the other hand, studies have shown that angiotensin antagonists such as losartan can improve memory and learning abilities. The aim of this study was to evaluate the effects of losartan on improving memory and leptin resistance induced by high fat diet in obese rats. 40 Wistar male rats were divided in 4 groups: control (C), losartan (LOS), high-fat diet (HFD) and high-fat diet and losartan (HFD and LOS). The spatial memory performances of the rats were assessed in the Morris water maze after 2 months of treatment. Then they were weighed and serum levels of leptin and triglyceride were measured. In spite of receiving high-fat diet, no significant differences in body weight were observed in the (HFD & LOS) group. In the Morris water maze trial, the (LOS) and (HFD & LOS) groups also showed a significant reduction (P <0.05) in latency and path length. In addition, a significant decrease (P <0.05) in serum levels of leptin and no significant difference in serum levels of triglyceride was observed in the (HFD & LOS) group. Losartan can improve leptin resistance induced by obesity and high fat diet. At the same time, it modulates body weight and enhances learning and memory.

Increased adipose tissue lipolysis after a 2-week high-fat diet in sedentary overweight/obese men.

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Howe, Harold R; Heidal, Kimberly; Choi, Myung Dong; Kraus, Ray M; Boyle, Kristen; Hickner, Robert C

2011-07-01

The purpose of this study was to determine if a high-fat diet would result in a higher lipolytic rate in subcutaneous adipose tissue than a lower-fat diet in sedentary nonlean men. Six participants (healthy males; 18-40 years old; body mass index, 25-37 kg/m(2)) underwent 2 weeks on a high-fat or well-balanced diet of similar energy content (approximately 6695 kJ) in randomized order with a 10-day washout period between diets. Subcutaneous abdominal adipose tissue lipolysis was determined over the course of a day using microdialysis after both 2-week diet sessions. Average interstitial glycerol concentrations (index of lipolysis) as determined using microdialysis were higher after the high-fat diet (210.8 ± 27.9 μmol/L) than after a well-balanced diet (175.6 ± 23.3 μmol/L; P = .026). There was no difference in adipose tissue microvascular blood flow as determined using the microdialysis ethanol technique. These results demonstrate that healthy nonlean men who diet on the high-fat plan have a higher lipolytic rate in subcutaneous abdominal adipose tissue than when they diet on a well-balanced diet plan. This higher rate of lipolysis may result in a higher rate of fat mass loss on the high-fat diet; however, it remains to be determined if this higher lipolytic rate in men on the high-fat diet results in a more rapid net loss of triglyceride from the abdominal adipose depots, or if the higher lipolytic rate is counteracted by an increased rate of lipid storage. Copyright © 2011 Elsevier Inc. All rights reserved.

High-protein, low-fat diets are effective for weight loss and favorably alter biomarkers in healthy adults.

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Johnston, Carol S; Tjonn, Sherrie L; Swan, Pamela D

2004-03-01

Although popular and effective for weight loss, low-carbohydrate, high-protein, high-fat (Atkins) diets have been associated with adverse changes in blood and renal biomarkers. High-protein diets low in fat may represent an equally appealing diet plan but promote a more healthful weight loss. Healthy adults (n = 20) were randomly assigned to 1 of 2 low-fat (vs. the high-carbohydrate diet (3.9 +/- 1.4 and 0.7 +/- 1.7 g N/d, respectively, P low-fat, energy-restricted diets of varying protein content (15 or 30% energy) promoted healthful weight loss, but diet satisfaction was greater in those consuming the high-protein diet.

Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat diet

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Yang Ching-Hsiu

2008-09-01

Full Text Available Abstract Background Pioglitazone was reported to improve hepatic steatosis and necroinflammation in human studies. To investigate whether the hepato-protective effect of pioglitazone was associated with an improvement of antioxidant defense mechanism, oxidative DNA damage and repair activity were determined in a high fat diet model. Male C57BL/6 mice were respectively fed with a 30% fat diet, the same diet with pioglitazone 100 mg/kg/day, or a chow diet as control for 8 weeks. Tissue oxidative stress was indicated by malondialdehyde concentration. Oxidative DNA damage was detected by immunohistochemical 8-oxoG staining. Enzymatic antioxidant defense was detected by the real-time PCR of superoxide dismutase (Sod1, Sod2 and DNA glycosylase (Ogg1, MutY. Oxidative DNA repair was detected by immunohistochemical staining and western blotting of OGG1 expression. Results Our results show that hepatic steatosis was induced by a high-fat diet and improved by adding pioglitazone. Malondialdehyde concentration and 8-oxoG staining were strongly increased in the high-fat diet group, but attenuated by pioglitazone. Gene expressions of antioxidant defense mechanism: Sod1, Sod2, Ogg1 and MutY significantly decreased in the high-fat diet group but reversed by pioglitazone co-administration. Conclusion The attenuation of hepatic oxidative DNA damage by pioglitazone in a high-fat diet may be mediated by up-regulation of the antioxidant defense mechanism and oxidative DNA repair activity. The diminution of oxidative damage may explain the clinical benefit of pioglitazone treatment in patients with non-alcoholic fatty liver disease.

Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat diet

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Hsiao, Pi-Jung; Hsieh, Tusty-Jiuan; Kuo, Kung-Kai; Hung, Wei-Wen; Tsai, Kun-Bow; Yang, Ching-Hsiu; Yu, Ming-Lung; Shin, Shyi-Jang

2008-01-01

Background Pioglitazone was reported to improve hepatic steatosis and necroinflammation in human studies. To investigate whether the hepato-protective effect of pioglitazone was associated with an improvement of antioxidant defense mechanism, oxidative DNA damage and repair activity were determined in a high fat diet model. Male C57BL/6 mice were respectively fed with a 30% fat diet, the same diet with pioglitazone 100 mg/kg/day, or a chow diet as control for 8 weeks. Tissue oxidative stress was indicated by malondialdehyde concentration. Oxidative DNA damage was detected by immunohistochemical 8-oxoG staining. Enzymatic antioxidant defense was detected by the real-time PCR of superoxide dismutase (Sod1, Sod2) and DNA glycosylase (Ogg1, MutY). Oxidative DNA repair was detected by immunohistochemical staining and western blotting of OGG1 expression. Results Our results show that hepatic steatosis was induced by a high-fat diet and improved by adding pioglitazone. Malondialdehyde concentration and 8-oxoG staining were strongly increased in the high-fat diet group, but attenuated by pioglitazone. Gene expressions of antioxidant defense mechanism: Sod1, Sod2, Ogg1 and MutY significantly decreased in the high-fat diet group but reversed by pioglitazone co-administration. Conclusion The attenuation of hepatic oxidative DNA damage by pioglitazone in a high-fat diet may be mediated by up-regulation of the antioxidant defense mechanism and oxidative DNA repair activity. The diminution of oxidative damage may explain the clinical benefit of pioglitazone treatment in patients with non-alcoholic fatty liver disease. PMID:18822121

Prior exercise training blunts short-term high-fat diet-induced weight gain.

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Snook, Laelie A; MacPherson, Rebecca E K; Monaco, Cynthia M F; Frendo-Cumbo, Scott; Castellani, Laura; Peppler, Willem T; Anderson, Zachary G; Buzelle, Samyra L; LeBlanc, Paul J; Holloway, Graham P; Wright, David C

2016-08-01

High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (-30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet. Copyright © 2016 the American Physiological Society.

Magnetic resonance spectroscopy detects differential lipid composition in mammary glands on low fat, high animal fat versus high fructose diets.

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Dianning He

Full Text Available The effects of consumption of different diets on the fatty acid composition in the mammary glands of SV40 T-antigen (Tag transgenic mice, a well-established model of human triple-negative breast cancer, were investigated with magnetic resonance spectroscopy and spectroscopic imaging. Female C3(1 SV40 Tag transgenic mice (n = 12 were divided into three groups at 4 weeks of age: low fat diet (LFD, high animal fat diet (HAFD, and high fructose diet (HFruD. MRI scans of mammary glands were acquired with a 9.4 T scanner after 8 weeks on the diet. 1H spectra were acquired using point resolved spectroscopy (PRESS from two 1 mm3 boxes on each side of inguinal mammary gland with no cancers, lymph nodes, or lymph ducts. High spectral and spatial resolution (HiSS images were also acquired from nine 1-mm slices. A combination of Gaussian and Lorentzian functions was used to fit the spectra. The percentages of poly-unsaturated fatty acids (PUFA, mono-unsaturated fatty acids (MUFA, and saturated fatty acids (SFA were calculated from each fitted spectrum. Water and fat peak height images (maps were generated from HiSS data. The results showed that HAFD mice had significantly lower PUFA than both LFD (p < 0.001 and HFruD (p < 0.01 mice. The mammary lipid quantity calculated from 1H spectra was much larger in HAFD mice than in LFD (p = 0.03 but similar to HFruD mice (p = 0.10. The average fat signal intensity over the mammary glands calculated from HiSS fat maps was ~60% higher in HAFD mice than in LFD (p = 0.04 mice. The mean or median of calculated parameters for the HFruD mice were between those for LFD and HAFD mice. Therefore, PRESS spectroscopy and HiSS MRI demonstrated water and fat composition changes in mammary glands due to a Western diet, which was low in potassium, high in sodium, animal fat, and simple carbohydrates. Measurements of PUFA with MRI could be used to evaluate cancer risk, improve cancer detection and diagnosis, and guide preventative

Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction.

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Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J; Liaw, Lucy

2012-09-28

We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

Diminished metabolic responses to centrally-administered apelin-13 in diet-induced obese rats fed a high-fat diet.

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Clarke, K J; Whitaker, K W; Reyes, T M

2009-02-01

The central administration of apelin, a recently identified adipokine, has been shown to affect food and water intake. The present study investigated whether body weight could affect an animal's response to apelin. The effects of centrally-administered apelin-13 on food and water intake, activity and metabolic rate were investigated in adult male diet-induced obese (DIO) rats fed either a high fat (32%) or control diet. Rats were administered i.c.v. apelin-13, 15-30 min prior to lights out, and food and water intake, activity and metabolic rate were assessed. Intracerebroventricular administration of apelin-13 decreased food and water intake and respiratory exchange ratio in DIO rats on the control diet, but had no effect in DIO rats on the high-fat diet. In an effort to identify potential central mechanisms explaining the observed physiological responses, the mRNA level of the apelin receptor, APJ, was examined in the hypothalamus. A high-fat diet induced an up-regulation of the expression of the receptor. Apelin induced a down-regulation of the receptor, but only in the DIO animals on the high-fat diet. In conclusion, we have demonstrated a diminished central nervous system response to apelin that is coincident with obesity.

Effects of Persian leek (Allium ampeloprasum) on hepatic lipids and the expression of proinflammatory gene in hamsters fed a high-fat/ high-cholesterol diet.

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Fatoorechi, Vahideh; Rismanchi, Marjan; Nasrollahzadeh, Javad

2016-01-01

Persian leek is one of the most widely used herbal foods among Iranians. In this study, effects of oral administration of Persian leek on plasma and liver lipids were examined in hamster. Male Syrian hamsters were randomly divided into three groups: control (standard diet), high fat control (high-fat/high-cholesterol diet), Persian leek (high-fat/high-cholesterol diet + 1% per weight of diet from dried powdered Persian leek) for 14 weeks. High fat diet increased plasma and liver lipids as compared to standard diet. Adding Persian leek to the high-fat/high-cholesterol diet resulted in no significant changes in the concentration of the plasma lipids or liver cholesterol. However, liver triglycerides (TG), plasma Alanine aminotransferase and gene expression of tumor necrosis factor- α were decreased in hamsters fed high-fat diet containing Persian leek as compared to high-fat diet only. Persian leek might be considered as a herbal food that can reduce liver TG accumulation induced by high fat diets.

High-fat diet determines the composition of the murine gut microbiome independently of obesity.

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Hildebrandt, Marie A; Hoffmann, Christian; Sherrill-Mix, Scott A; Keilbaugh, Sue A; Hamady, Micah; Chen, Ying-Yu; Knight, Rob; Ahima, Rexford S; Bushman, Frederic; Wu, Gary D

2009-11-01

The composition of the gut microbiome is affected by host phenotype, genotype, immune function, and diet. Here, we used the phenotype of RELMbeta knockout (KO) mice to assess the influence of these factors. Both wild-type and RELMbeta KO mice were lean on a standard chow diet, but, upon switching to a high-fat diet, wild-type mice became obese, whereas RELMbeta KO mice remained comparatively lean. To investigate the influence of diet, genotype, and obesity on microbiome composition, we used deep sequencing to characterize 25,790 16S rDNA sequences from uncultured bacterial communities from both genotypes on both diets. We found large alterations associated with switching to the high-fat diet, including a decrease in Bacteroidetes and an increase in both Firmicutes and Proteobacteria. This was seen for both genotypes (ie, in the presence and absence of obesity), indicating that the high-fat diet itself, and not the obese state, mainly accounted for the observed changes in the gut microbiota. The RELMbeta genotype also modestly influenced microbiome composition independently of diet. Metagenomic analysis of 537,604 sequence reads documented extensive changes in gene content because of a high-fat diet, including an increase in transporters and 2-component sensor responders as well as a general decrease in metabolic genes. Unexpectedly, we found a substantial amount of murine DNA in our samples that increased in proportion on a high-fat diet. These results demonstrate the importance of diet as a determinant of gut microbiome composition and suggest the need to control for dietary variation when evaluating the composition of the human gut microbiome.

Methyl donor supplementation blocks the adverse effects of maternal high fat diet on offspring physiology.

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Jesselea Carlin

Full Text Available Maternal consumption of a high fat diet during pregnancy increases the offspring risk for obesity. Using a mouse model, we have previously shown that maternal consumption of a high fat (60% diet leads to global and gene specific decreases in DNA methylation in the brain of the offspring. The present experiments were designed to attempt to reverse this DNA hypomethylation through supplementation of the maternal diet with methyl donors, and to determine whether methyl donor supplementation could block or attenuate phenotypes associated with maternal consumption of a HF diet. Metabolic and behavioral (fat preference outcomes were assessed in male and female adult offspring. Expression of the mu-opioid receptor and dopamine transporter mRNA, as well as global DNA methylation were measured in the brain. Supplementation of the maternal diet with methyl donors attenuated the development of some of the adverse effects seen in offspring from dams fed a high fat diet; including weight gain, increased fat preference (males, changes in CNS gene expression and global hypomethylation in the prefrontal cortex. Notable sex differences were observed. These findings identify the importance of balanced methylation status during pregnancy, particularly in the context of a maternal high fat diet, for optimal offspring outcome.

High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

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Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

2015-11-01

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis. Copyright © 2015 the American Physiological Society.

Ghrelin signaling in the ventral tegmental area mediates both reward-based feeding and fasting-induced hyperphagia on high-fat diet.

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Wei, X J; Sun, B; Chen, K; Lv, B; Luo, X; Yan, J Q

2015-08-06

Ghrelin is a potent orexigenic hormone that acts in the central nervous system to stimulate food intake via the growth hormone secretagogue receptor (GHSR) that is abundantly expressed in the ventral tegmental area (VTA). Not only does ghrelin modulate feeding behavior via a homeostatic mechanism, but numerous studies have identified ghrelin as a key regulator of reward-based hedonic feeding behaviors. Nutritional states influence ghrelin and GHSR expression as well as the behavioral sensitivity to reward-inducing stimuli. In the current study, we examined the role of ghrelin at the VTA level in food intake in two different nutritional states, satiety and hunger, by using a restricted feeding model. In this model, rats were conditioned to a daily 3-h (h) feeding session on standard chow for 10days and a high-fat diet (HFD) was supplied either in the third hour after 2h of chow diet intake, or at the beginning of a daily meal on the test day. We found that intra-VTA microinjection of 1, 2, and 4μg of ghrelin, induced a dose-related increase of 1h of reward-based feeding on HFD in sated rats, as well as a 24-h body weight gain. The overconsumption stimulated by ghrelin could be attenuated by 10μg of direct infusion of the ghrelin receptor antagonist D-Lys3-GHRP-6 into the VTA. Moreover, our data showed that the injection of 1, 2, and 4μg of ghrelin in the VTA, enhanced fasting-induced hyperphagia on HFD in a dose-related manner following a 21-h food restriction as well as a 24-h body weight gain. Conversely, hyperphagia on HFD that is potentiated by ghrelin could be blocked by pretreatment with a 10-μg D-Lys3-GHRP-6 intra-VTA microinjection. Collectively, these data demonstrate that ghrelin signaling at the VTA level mediates both reward-based eating and fasting-induced hyperphagia and provides a primary target for the control of the intake of rewarding food. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia

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La Fleur, S. E.; van Rozen, A. J.; Luijendijk, M. C. M.; Groeneweg, F.; Adan, R. A. H.

2010-01-01

The mechanisms for how saturated fat and sugar-based beverages contribute to human obesity are poorly understood. This paper describes a series of experiments developed to examine the response of hypothalamic neuropeptides to diets rich in sugar and fat, using three different diets: a high-fat

Differential effects of short- and long-term high-fat diet feeding on hepatic fatty acid metabolism in rats

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Ciapaite, Jolita; van den Broek, Nicole M.; te Brinke, Heleen; Nicolay, Klaas; Jeneson, Jeroen A.; Houten, Sander M.; Prompers, Jeanine J.

2011-01-01

Imbalance in the supply and utilization of fatty acids (FA) is thought to contribute to intrahepatic lipid (IHL) accumulation in obesity. The aim of this study was to determine the time course of changes in the liver capacity to oxidize and store FA in response to high-fat diet (HFD). Adult male

High fat diet and GLP-1 drugs induce pancreatic injury in mice

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Rouse, Rodney, E-mail: rodney.rouse@fda.hhs.gov; Xu, Lin; Stewart, Sharron; Zhang, Jun

2014-04-15

Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment.

High fat diet and GLP-1 drugs induce pancreatic injury in mice

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Rouse, Rodney; Xu, Lin; Stewart, Sharron; Zhang, Jun

2014-01-01

Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment

Tangeretin and 3',4',3,5,6,7,8-heptamethoxyflavone decrease insulin resistance, fat accumulation and oxidative stress in mice fed high-fat diet

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Tangeretin and heptamethoxyflavone were investigated for their ability to repair metabolic damage caused by high-fat diet in C57BL/6J mice. In the first four weeks, induction of obesity was performed and the mice received standard diet (11% kcal from fat) or high-fat diet (45% kcal from fat). After ...

Lessons from Mouse Models of High-Fat Diet-Induced NAFLD

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Yasuo Terauchi

2013-10-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD encompasses a clinicopathologic spectrum of diseases ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH, the more aggressive form of fatty liver disease that may progress to cirrhosis and cirrhosis-related complications, including hepatocellular carcinoma. The prevalence of NAFLD, including NASH, is also increasing in parallel with the growing epidemics of obesity and diabetes. However, the causal relationships between obesity and/or diabetes and NASH or liver tumorigenesis have not yet been clearly elucidated. Animal models of NAFLD/NASH provide crucial information, not only for elucidating the pathogenesis of NAFLD/NASH, but also for examining therapeutic effects of various agents. A high-fat diet is widely used to produce hepatic steatosis and NASH in experimental animals. Several studies, including our own, have shown that long-term high-fat diet loading, which can induce obesity and insulin resistance, can also induce NASH and liver tumorigenesis in C57BL/6J mice. In this article, we discuss the pathophysiology of and treatment strategies for NAFLD and subsequent NAFLD-related complications such as NASH and liver tumorigenesis, mainly based on lessons learned from mouse models of high-fat diet-induced NAFLD/NASH.

Perinatal exposure to a diet high in saturated fat, refined sugar and cholesterol affects behaviour, growth, and feed intake in weaned piglets

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Clouard, Caroline; Gerrits, Walter J.J.; Kemp, Bas; Val-Laillet, David; Bolhuis, J.E.

2016-01-01

The increased consumption of diets high in saturated fats and refined sugars is a major public health concern in Western human societies. Recent studies suggest that perinatal exposure to dietary fat and/or sugar may affect behavioural development. We thus investigated the effects of perinatal

Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats

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Mohd Nazri Abu

2015-01-01

Full Text Available The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC which received standard rodent diet, the high fat diet (HFD which received high fat diet only, the high fat diet treated with T. crispa (HFDTC, and the high fat diet treated with orlistat (HFDO. After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05 reduced the body weight (41.14 ± 1.40%, adiposity index serum levels (4.910 ± 0.80%, aspartate aminotransferase (AST: 161 ± 4.71 U/L, alanine aminotransferase (ALT: 100.95 ± 3.10 U/L, total cholesterol (TC: 18.55 ± 0.26 mmol/L, triglycerides (TG: 3.70 ± 0.11 mmol/L, blood glucose (8.50 ± 0.30 mmo/L, resistin (0.74 ± 0.20 ng/mL, and leptin (17.428 ± 1.50 ng/mL hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL and C-peptide (136.48 pmol/L hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet.

Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins.

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Lanham, S A; Cagampang, F R; Oreffo, R O C

2014-12-01

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

Swimming exercise increases serum irisin level and reduces body fat mass in high-fat-diet fed Wistar rats.

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Lu, Yun; Li, Hongwei; Shen, Shi-Wei; Shen, Zhen-Hai; Xu, Ming; Yang, Cheng-Jian; Li, Feng; Feng, Yin-Bo; Yun, Jing-Ting; Wang, Ling; Qi, Hua-Jin

2016-05-13

It has been shown that irisin levels are reduced in skeletal muscle and plasma of obese rats; however, the effect of exercise training on irisin level remains controversial. We aim to evaluate the association of swimming exercise with serum irisin level and other obesity-associated parameters. Forty healthy male Wistar rats were randomly assigned to 4 groups: a normal diet and sedentary group (ND group), normal diet and exercise group (NDE group), high-fat diet and sedentary group (HFD group), and high-fat diet and exercise group (HFDE group. After 8 consecutive weeks of swimming exercise, fat mass and serum irisin level was determined. Higher serum irisin levels were detected in the HFDE group (1.15 ± 0.28 μg/L) and NDE group (1.76 ± 0.17 μg/L) than in the HFD group (0.84 ± 0.23 μg/L) or the ND group (1.24 ± 0.29 μg/L), respectively (HFDE group vs. HFD group, P mass (r = -0.68, P mass (r = -0.576, P mass (r = -0.439, P mass, visceral fat mass and percentage fat mass were lower in the HFDE group than the HFD group (all P values mass in high-fat-fed Wistar rats, which may be attributable to elevated irisin levels induced by swimming exercise.

Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

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Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

2015-03-18

Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright �

Effect of high fat diet on pulmonary expression of parathyroid hormone-related protein and its downstream targets

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Learta Oruqaj

2016-10-01

Full Text Available Aims: Parathyroid hormone-related protein (PTHrP is involved in lung development and surfactant production. The latter one requires a paracrine interaction between type II alveolar cells and lipofibroblasts in which leptin triggers PTHrP-induced effects. Whether increased plasma leptin levels, as they occur in high fat diet, modify the expression of PTHrP remains unclear. Furthermore, the effect of high fat diet under conditions of forced pulmonary remodelling such as response to post myocardial infarction remains to be defined. Materials and methods: C57 bl/6 mice were randomized to either normal diet or high fat diet at an age of 6 weeks. Seven months later, the mice were euthanized and the lung was removed and frozen in fluid nitrogen until use. Samples were analyzed by real-time RT-PCR and western blot. Leptin deficient mice were used to investigate the effect of leptin on pulmonary expression of PTHrP more directly. A subgroup of mice with and without high fat diet underwent in vivo ischemia (45 min and reperfusion (4 weeks. Finally, experiments were repeated with prolonged high-fat diet. Key findings: High fat diet increased plasma leptin levels by 30.4% and the pulmonary mRNA expression of PTHrP (1,447-fold, PTH-1 receptor (4.21-fold, and PTHrP-downstream targets ADRP (7.54-fold and PPARγ (5.27-fold. Pulmonary PTHrP expression was reduced in leptin deficient mice by 88% indicating leptin dependent regulation. High fat diet further improved changes in pulmonary adaptation caused by ischemia/reperfusion (1.48-fold increased PTH-1 receptor protein expression. These effects were lost during prolonged high fat diet. Significance: This study established that physiological regulation of leptin plasma levels by high fat diet affects the pulmonary PTHrP expression and of PTHrP downstream targets. Modification of pulmonary expression of PTH-1 receptors by high fat diet after myocardial infarction suggests that the identified interaction may

High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

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Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Mehendale, Harihara M.

2008-01-01

Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD 10 dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-α, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 ± 14.0 nmol/min/g heart in ND versus 400.2 ± 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-α2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3

The effects of chromium complex and level on glucose metabolism and memory acquisition in rats fed high-fat diet.

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Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Agca, Can A; Sahin, Nurhan; Guvenc, Mehmet; Krejpcio, Zbigniew; Staniek, Halina; Hayirli, Armagan

2011-11-01

Conditions in which glucose metabolism is impaired due to insulin resistance are associated with memory impairment. It was hypothesized that supplemental chromium (Cr) may alleviate insulin resistance in type 2 diabetes and consequently improve memory acquisition, depending upon its source and level. In a complete randomized design experiment, male Wistar rats (n=60; weighing 200-220 g) were fed either normal (8%, normal diet (ND)) or high-fat (40%, high-fat diet (HFD)) diet and supplemented with Cr as either chromium-glycinate (CrGly) or chromium-acetate (CrAc) at doses of 0, 40, or 80 μg/kg body weight (BW) via drinking water from 8 to 20 weeks of age. Feeding HFD induced type 2 diabetes, as reflected by greater glucose/insulin ratio (2.98 vs. 2.74) comparing to feeding ND. Moreover, HFD rats had greater BW (314 vs. 279 g) and less serum (53 vs. 68 μg/L) and brain (14 vs. 24 ng/g) Cr concentrations than ND rats. High-fat diet caused a 32% reduction in expressions of glucose transporters 1 and 3 (GLUTs) in brain tissue and a 27% reduction in mean percentage time spent in the target quadrant and a 38% increase in spatial memory acquisition phase (SMAP) compared with ND. Compared with supplemental Cr as CrAc, CrGly was more effective to ameliorate response variables (i.e., restoration of tissue Cr concentration, enhancement of cerebral GLUTs expressions, and reduction of the glucose/insulin ratio and SMAP) in a dose-response manner, especially in rats fed HFD. Supplemental Cr as CrGly may have therapeutic potential to enhance insulin action and alleviate memory acquisition in a dose-dependent manner, through restoring tissue Cr reserve and enhancing cerebral GLUTs expressions.

Development of hepatocellular cancer induced by long term low fat-high carbohydrate diet in a NAFLD/NASH mouse model.

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Tessitore, Alessandra; Mastroiaco, Valentina; Vetuschi, Antonella; Sferra, Roberta; Pompili, Simona; Cicciarelli, Germana; Barnabei, Remo; Capece, Daria; Zazzeroni, Francesca; Capalbo, Carlo; Alesse, Edoardo

2017-08-08

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. It can progress to nonalcoholic steatohepatitis (NASH) and, in a percentage of cases, to hepatocarcinogenesis. The strong incidence in western countries of obesity and metabolic syndrome, whose NAFLD is the hepatic expression, is thought to be correlated to consumption of diets characterized by processed food and sweet beverages. Previous studies described high-fat diet-induced liver tumors. Conversely, the involvement of low-fat/high-carbohydrate diet in the progression of liver disease or cancer initiation has not been described yet. Here we show for the first time hepatic cancer formation in low-fat/high-carbohydrate diet fed NAFLD/NASH mouse model. Animals were long term high-fat, low-fat/high-carbohydrate or standard diet fed. We observed progressive liver damage in low-fat/high-carbohydrate and high-fat animals after 12 and, more, 18 months. Tumors were detected in 20% and 50% of high-fat diet fed mice after 12 and 18 months and, interestingly, in 30% of low-fat/high-carbohydrate fed animals after 18 months. No tumors were detected in standard diet fed mice. Global increase of hepatic interleukin-1β, interleukin-6, tumor necrosis factor-α and hepatocyte growth factor was detected in low-fat/high-carbohydrate and high-fat with respect to standard diet fed mice as well as in tumor with respect to non-tumor bearing mice. A panel of 15 microRNAs was analyzed: some of them revealed differential expression in low-fat/high-carbohydrate with respect to high-fat diet fed groups and in tumors. Data here shown provide the first evidence of the involvement of low-fat/high-carbohydrate diet in hepatic damage leading to tumorigenesis.

Berberine improves insulin resistance induced by high fat diet in rats

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Zhou Libin; Yang Ying; Shang Wenbin; Li Fengying; Tang Jinfeng; Wang Xiao; Liu Shangquan; Yuan Guoyue; Chen Mingdao

2005-01-01

Objective: To observe the effect of berberine on insulin resistance induced by high fat diet in rats. Methods: Normal male SD rats (8 weeks old) were divided into two groups taking either normal chow (NC, n=9) or high fat diet (HF, n=20). After fourteen weeks, HF rats were divided into two groups. Ten rats continued to take high fat diet. Another ten rats took additional berberine gavage (HF+B, 150mg/kg weight once a day). Six weeks later, oral glucose tolerance test and insulin tolerance test were performed for estimating insulin sensitivity. Results: The body weight, liver weight and epididyaml fat pads weight of HF group were significantly higher than those of HF+B group and NC group (all P<0.01). Fasting plasma glucose, insulin and plasma glucose, insulin 2h after taking glucose in HF+B rats were significantly lower than those in HF rats (all P<0.01). Plasma glucose and insulin levels at all time points in HF rats were significantly higher than those in NC rats. Homa-IR of HF group was markedly higher than that of HF+B group (P<0.01). The glucose-lowering effects after the administration of insuin (0.5u/kg intrapenitoneally) at all time points in HF+B rats were stronger than those in HF rats with 23% and 7% reduction at 15min respectively. Conclusion: Long term high fat diet resulted in insulin resistance. Berberine was able to reverse insulin resistance through promoting peripheral tissue up taking of glucose and decreasing insulin, which would be quite ideal for the intervention of IGT. (authors)

Antioxidative Diet Supplementation Reverses High-Fat Diet-Induced Increases of Cardiovascular Risk Factors in Mice

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Hilda Vargas-Robles

2015-01-01

Full Text Available Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD. Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.

High-fructose diet is as detrimental as high-fat diet in the induction of insulin resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER) stress.

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Balakumar, M; Raji, L; Prabhu, D; Sathishkumar, C; Prabu, P; Mohan, V; Balasubramanyam, M

2016-12-01

In the context of high human consumption of fructose diets, there is an imperative need to understand how dietary fructose intake influence cellular and molecular mechanisms and thereby affect β-cell dysfunction and insulin resistance. While evidence exists for a relationship between high-fat-induced insulin resistance and metabolic disorders, there is lack of studies in relation to high-fructose diet. Therefore, we attempted to study the effect of different diets viz., high-fat diet (HFD), high-fructose diet (HFS), and a combination (HFS + HFD) diet on glucose homeostasis and insulin sensitivity in male Wistar rats compared to control animals fed with normal pellet diet. Investigations include oral glucose tolerance test, insulin tolerance test, histopathology by H&E and Masson's trichrome staining, mRNA expression by real-time PCR, protein expression by Western blot, and caspase-3 activity by colorimetry. Rats subjected to high-fat/fructose diets became glucose intolerant, insulin-resistant, and dyslipidemic. Compared to control animals, rats subjected to different combination of fat/fructose diets showed increased mRNA and protein expression of a battery of ER stress markers both in pancreas and liver. Transcription factors of β-cell function (INSIG1, SREBP1c and PDX1) as well as hepatic gluconeogenesis (FOXO1 and PEPCK) were adversely affected in diet-induced insulin-resistant rats. The convergence of chronic ER stress towards apoptosis in pancreas/liver was also indicated by increased levels of CHOP mRNA & increased activity of both JNK and Caspase-3 in rats subjected to high-fat/fructose diets. Our study exposes the experimental support in that high-fructose diet is equally detrimental in causing metabolic disorders.

Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes

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Nuernberg Karin

2011-08-01

Full Text Available Abstract Background Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue. Methods The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6 leading to rapid obesity development, or selected for high treadmill performance (DUhTP leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein, or a high-fat diet rich in n-3 PUFA (n-3 HFD, 27.7% fat, 19% protein or a high-fat diet rich in n-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways. Results Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor β protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue. Conclusions A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.

Effect of High Fat and High Sugar Diet on Glucose Tolerance, Insulin Response to Glucose Load and Insulin Sensitivity in Rats

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岡﨑, 悟

1987-01-01

To investigate the precipitating effects of the westernized diet on diabetes mellitus, glucose tolerance and insulin response to oral glucose load (1.5g/kg body weight) and insulin sensitivity to exogenous insulin (0.2U/kg) were studied in rats fed an experimental diet for 8 weeks. Four experimental diets were used : low fat-no sugar diet (energy ratio of 10% fat, 70% starch, a model of the traditional Japanese diet), high fat-high sugar diet (40% fat, 20% starch, 20% sugar, a model of the we...

Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice.

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Kim, Misung; Na, Woori; Sohn, Cheongmin

2013-09-01

Several reports suggest that obesity is a risk factor for osteoporosis. Vitamin K plays an important role in improving bone metabolism. This study examined the effects of vitamin K1 and vitamin K2 supplementation on the biochemical markers of bone turnover and morphological microstructure of the bones by using an obese mouse model. Four-week-old C57BL/6J male mice were fed a 10% fat normal diet group or a 45% kcal high-fat diet group, with or without 200 mg/1000 g vitamin K1 (Normal diet + K1, high-fat diet + K1) and 200 mg/1000 g vitamin K2 (Normal diet + K2, high-fat diet + K2) for 12 weeks. Serum levels of osteocalcin were higher in the high-fat diet + K2 group than in the high-fat diet group. Serum OPG level of the high-fat diet group, high-fat diet + K1 group, and high-fat diet + K2 group was 2.31 ± 0.31 ng/ml, 2.35 ± 0.12 ng/ml, and 2.90 ± 0.11 ng/ml, respectively. Serum level of RANKL in the high-fat diet group was significantly higher than that in the high-fat diet + K1 group and high-fat diet + K2 group (p<0.05). Vitamin K supplementation seems to tend to prevent bone loss in high-fat diet induced obese state. These findings suggest that vitamin K supplementation reversed the high fat diet induced bone deterioration by modulating osteoblast and osteoclast activities and prevent bone loss in a high-fat diet-induced obese mice.

Hunger and satiety responses to high-fat meals after a high-polyunsaturated fat diet: A randomized trial.

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Stevenson, Jada L; Paton, Chad M; Cooper, Jamie A

2017-09-01

Previous studies have shown that polyunsaturated fats (PUFAs) elicit a greater response in satiety after a single-meal challenge compared with other types of fats. The long-term effects of PUFAs on satiety, however, remain unknown. The aim of this study was to determine subjective and physiological hunger and satiety responses to high-fat (HF) meals before and after a 7-d PUFA-rich diet. Twenty-six, healthy weight (body mass index 18-24.9 kg/m 2 ), sedentary adults were randomly assigned to either a 7-d PUFA-rich diet (n = 8 men and n = 8 women) or a 7-d control diet (n = 5 men and n = 5 women). After a 3-d lead-in diet, participants reported for the baseline visit where anthropometrics, fasting visual analog scale (VAS) measurements, and a fasting blood sample were collected. Then, two HF meals (breakfast and lunch) were consumed. Postprandial blood draws and VAS measures were collected approximately every 30 min for 4 h after each meal, for a total of 8 h. From pre- to post-PUFA-rich diet, there was a decrease in fasting ghrelin (P hunger and satiety; yet, did not alter subjective ratings of hunger or fullness. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis.

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Liśkiewicz, Arkadiusz D; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin-Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska-Szypułka, Halina

2016-02-19

Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.

Exercise reverses metabolic syndrome in high-fat diet-induced obese rats.

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Touati, Sabeur; Meziri, Fayçal; Devaux, Sylvie; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal

2011-03-01

Chronic consumption of a high-fat diet induces obesity. We investigated whether exercise would reverse the cardiometabolic disorders associated with obesity without it being necessary to change from a high- to normal-fat diet. Sprague-Dawley rats were placed on a high-fat (HFD) or control diet (CD) for 12 wk. HFD rats were then divided into four groups: sedentary HFD (HFD-S), exercise trained (motor treadmill for 12 wk) HFD (HFD-Ex), modified diet (HFD to CD; HF/CD-S), and exercise trained with modified diet (HF/CD-Ex). Cardiovascular risk parameters associated with metabolic syndrome were measured, and contents of aortic Akt, phospho-Akt at Ser (473), total endothelial nitric oxide synthase (eNOS), and phospho-eNOS at Ser (1177) were determined by Western blotting. Chronic consumption of HFD induced a metabolic syndrome. Exercise and dietary modifications reduced adiposity, improved glucose and insulin levels and plasma lipid profile, and exerted an antihypertensive effect. Exercise was more effective than dietary modification in improving plasma levels of thiobarbituric acid-reacting substance and in correcting the endothelium-dependent relaxation to acetylcholine and insulin. Furthermore, independent of the diet used, exercise increased Akt and eNOS phosphorylation. Metabolic syndrome induced by HFD is reversed by exercise and diet modification. It is demonstrated that exercise training induces these beneficial effects without the requirement for dietary modification, and these beneficial effects may be mediated by shear stress-induced Akt/eNOS pathway activation. Thus, exercise may be an effective strategy to reverse almost all the atherosclerotic risk factors linked to obesity, particularly in the vasculature.

High-fat feeding impairs nutrient sensing and gut brain integration in the caudomedial nucleus of the solitary tract in mice.

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Althea R Cavanaugh

Full Text Available Hyperphagic obesity is characterized in part by a specific increase in meal size that contributes to increased daily energy intake, but the mechanisms underlying impaired activity of meal size regulatory circuits, particularly those converging at the caudomedial nucleus of the solitary tract in the hindbrain (cmNTS, remain poorly understood. In this paper, we assessed the consequences of high-fat (HF feeding and diet-induced obesity (DIO on cmNTS nutrient sensing and metabolic integration in the control of meal size. Mice maintained on a standard chow diet, low-fat (LF diet or HF diet for 2 weeks or 6 months were implanted with a bilateral brain cannula targeting the cmNTS. Feeding behavior was assessed using behavioral chambers and meal-pattern analysis following cmNTS L-leucine injections alone or together with ip CCK. Molecular mechanisms implicated in the feeding responses were assessed using western blot, immunofluorescence and pharmacological inhibition of the amino acid sensing mTORC1 pathway (mammalian target of rapamycin complex 1. We found that HF feeding blunts the anorectic consequences of cmNTS L-leucine administration. Increased baseline activity of the L-leucine sensor P70 S6 kinase 1 and impaired L-leucine-induced activation of this pathway in the cmNTS of HF-fed mice indicate that HF feeding is associated with an impairment in cmNTS mTOR nutritional and hormonal sensing. Interestingly, the acute orexigenic effect of the mTORC1 inhibitor rapamycin was preserved in HF-fed mice, supporting the assertion that HF-induced increase in baseline cmNTS mTORC1 activity underlies the defect in L-leucine sensing. Last, the synergistic feeding-suppressive effect of CCK and cmNTS L-leucine was abrogated in DIO mice. These results indicate that HF feeding leads to an impairment in cmNTS nutrient sensing and metabolic integration in the regulation of meal size.

Effect of berberine on the ratio of high-molecular weight adiponectin to total adiponectin and adiponectin receptors expressions in high-fat diet fed rats.

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Wu, Yue-Yue; Zha, Ying; Liu, Jun; Wang, Fang; Xu, Jiong; Chen, Zao-Ping; Ding, He-Yuan; Sheng, Li; Han, Xiao-Jie

2016-11-17

To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg -1 ·day -1 BBR (HF+LBBR group) and 380 mg·kg -1 ·day -1 BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment. The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (Pinsulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.

Effects of high-fat diet and physical activity on pyruvate dehydrogenase kinase-4 in mouse skeletal muscle

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Rinnankoski-Tuikka Rita

2012-06-01

Full Text Available Abstract Background The expression of PDK4 is elevated by diabetes, fasting and other conditions associated with the switch from the utilization of glucose to fatty acids as an energy source. It is previously shown that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, a master regulator of energy metabolism, coactivates in cell lines pyruvate dehydrogenase kinase-4 (PDK4 gene expression via the estrogen-related receptor α (ERRα. We investigated the effects of long-term high-fat diet and physical activity on the expression of PDK4, PGC-1α and ERRα and the amount and function of mitochondria in skeletal muscle. Methods Insulin resistance was induced by a high-fat (HF diet for 19 weeks in C57BL/6 J mice, which were either sedentary or with access to running wheels. The skeletal muscle expression levels of PDK4, PGC-1α and ERRα were measured and the quality and quantity of mitochondrial function was assessed. Results The HF mice were more insulin-resistant than the low-fat (LF -fed mice. Upregulation of PDK4 and ERRα mRNA and protein levels were seen after the HF diet, and when combined with running even more profound effects on the mRNA expression levels were observed. Chronic HF feeding and voluntary running did not have significant effects on PGC-1α mRNA or protein levels. No remarkable difference was found in the amount or function of mitochondria. Conclusions Our results support the view that insulin resistance is not mediated by the decreased qualitative or quantitative properties of mitochondria. Instead, the role of PDK4 should be contemplated as a possible contributor to high-fat diet-induced insulin resistance.

Maternal low protein diet and postnatal high fat diet increases adipose imprinted gene expression

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Maternal and postnatal diet can alter Igf2 gene expression and DNA methylation. To test whether maternal low protein and postnatal high fat (HF) diet result in alteration in Igf2 expression and obesity, we fed obese-prone Sprague-Dawley rats 8% (LP) or 20% (NP) protein for 3 wk prior to breeding and...

Modification of high saturated fat diet with n-3 polyunsaturated fat improves glucose intolerance and vascular dysfunction

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Lamping, KL; Nuno, DW; Coppey, LJ; Holmes, AJ; Hu, S; Oltman, CL; Norris, AW; Yorek, MA

2013-01-01

Aims The ability of dietary enrichment with monounsaturated (MUFA), n-3, or n-6 polyunsaturated fatty acids (PUFA) to reverse glucose intolerance and vascular dysfunction resulting from excessive dietary saturated fatty acids is not resolved. We hypothesized that partial replacement of dietary saturated fats with n-3 PUFA enriched menhaden oil (MO) would provide greater improvement in glucose tolerance and vascular function compared to n-6 enriched safflower oil (SO) or MUFA-enriched olive oil (OO). Material and Methods We fed mice a high saturated fat diet (60% kcal from lard) for 12 weeks before substituting half the lard with MO, SO or OO for an additional 4 weeks. At the end of 4 weeks, we assessed glucose tolerance, insulin signaling and reactivity of isolated pressurized gracilis arteries. Results After 12 weeks of saturated fat diet, body weights were elevated and glucose tolerance abnormal compared to mice on control diet (13% kcal lard). Diet substituted with MO restored basal glucose levels, glucose tolerance, and indices of insulin signaling (phosphorylated Akt) to normal whereas restoration was limited for SO and OO substitutions. Although dilation to acetylcholine was reduced in arteries from mice on HF, OO and SO diets compared to normal diet, dilation to acetylcholine was fully restored and constriction to phenylephrine reduced in MO fed mice compared to normal. Conclusion We conclude that short term enrichment of an ongoing high fat diet with n-3 PUFA rich MO but not MUFA rich OO or n-6 PUFA rich SO reverses glucose tolerance, insulin signaling, and vascular dysfunction. PMID:22950668

Withdrawal from high-carbohydrate, high-saturated-fat diet changes saturated fat distribution and improves hepatic low-density-lipoprotein receptor expression to ameliorate metabolic syndrome in rats.

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Hazarika, Ankita; Kalita, Himadri; Kalita, Mohan Chandra; Devi, Rajlakshmi

2017-06-01

The "lipid hypothesis" determined that saturated fatty acid (SFA) raises low-density lipoprotein cholesterol, thereby increasing the risk for metabolic syndrome (MetS). The aim of this study was to investigate the effect of subchronic withdrawal from a high-carbohydrate, high-saturated fat (HCHF) diet during MetS with reference to changes in deleterious SFA (C12:0, lauric acid; C14:0, myristic acid; C16:0, palmitic acid; C18:0, stearic acid) distribution in liver, white adipose tissue (WAT), and feces. MetS induced by prolonged feeding of an HCHF diet in Wistar albino rat is used as a model of human MetS. The MetS-induced rats were withdrawn from the HCHF diet and changed to a basal diet for final 4 wk of the total experimental duration of 16 wk. SFA distribution in target tissues and hepatic low-density lipoprotein receptor (LDLr) expression were analyzed. Analyses of changes in SFA concentration of target tissues indicate that C16:0 and C18:0 reduced in WAT and liver after withdrawal of the HCHF diet. There was a significant (P < 0.001) decrease in fecal C12:0 with HCHF feeding, which significantly (P < 0.01) increased after withdrawal of this diet. Also, an improvement in expression of hepatic LDLr was observed after withdrawal of HCHF diet. The prolonged consumption of an HCHF diet leads to increased SFA accumulation in liver and WAT, decreased SFA excretion, and reduced hepatic LDLr expression during MetS, which is prominently reversed after subchronic withdrawal of the HCHF diet. This can contribute to better understanding of the metabolic fate of dietary SFA during MetS and may apply to the potential reversal of complications by the simple approach of nutritional modification. Copyright © 2017 Elsevier Inc. All rights reserved.

High fat diet-induced obesity reduces bone formation through activation of ppar gamma to suppress wnt/beta-catenin signaling in prepubertal rats

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The effects of a high fat diet (HFD) and of obesity on skeletal development, maturation and remodeling remain largely unclear particularly in children. In this report, we utilized a total enteral nutrition (TEN) model to examine the direct effect of HFD feeding on bone prior to puberty. We chronical...

Randomized, multi-center trial of two hypo-energetic diets in obese subjects: high- versus low-fat content

DEFF Research Database (Denmark)

Petersen, M; Taylor, M A; Saris, W H M

2006-01-01

:Obese (BMI >or=30 kg/m(2)) adult subjects (n = 771), from eight European centers. MEASUREMENTS: Body weight loss, dropout rates, proportion of subjects who lost more than 10% of initial body weight, blood lipid profile, insulin and glucose. RESULTS: The dietary fat energy percent was 25% in the low-fat group...... and 40% in the high-fat group (mean difference: 16 (95% confidence interval (CI) 15-17)%). Average weight loss was 6.9 kg in the low-fat group and 6.6 kg in the high-fat group (mean difference: 0.3 (95% CI -0.2 to 0.8) kg). Dropout was 13.6% (n = 53) in the low-fat group and 18.3% (n = 70) in the high......-fat group than in the high-fat group. Fasting plasma insulin and glucose were lowered equally by both diets. CONCLUSIONS: The low-fat diet produced similar mean weight loss as the high-fat diet, but resulted in more subjects losing >10% of initial body weight and fewer dropouts. Both diets produced...

Effects of high fat diet on incidence of spontaneous tumors in Wistar rats

DEFF Research Database (Denmark)

KRISTIANSEN, E.; Madsen, Charlotte Bernhard; Meyer, Otto A.

1993-01-01

In a 2.5-year carcinogenicity study, two groups, both including male and female Wistar rats, were fed two different diets with 4% and 16% fat. In addition to 4% soybean oil, the high-fat diet contained 12% mono- and diglycerides, of which 85% was stearic acid and 13% palmitic acid...

Effect of High-Fat Diet upon Inflammatory Markers and Aortic Stiffening in Mice

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Andre Bento Chaves Santana

2014-01-01

Full Text Available Changes in lifestyle such as increase in high-fat food consumption are an important cause for vascular diseases. The present study aimed to investigate the involvement of ACE and TGF-β in the aorta stiffness induced by high-fat diet. C57BL/6 male mice were divided in two groups according to their diet for 8 weeks: standard diet (ST and high-fat diet (HF. At the end of the protocol, body weight gain, adipose tissue content, serum lipids and glucose levels, and aorta morphometric and biochemical measurements were performed. Analysis of collagen fibers by picrosirius staining of aorta slices showed that HF diet promoted increase of thin (55% and thick (100% collagen fibers deposition and concomitant disorganization of these fibers orientations in the aorta vascular wall (50%. To unravel the mechanism involved, myeloperoxidase (MPO and angiotensin I converting enzyme (ACE were evaluated by protein expression and enzyme activity. HF diet increased MPO (90% and ACE (28% activities, as well as protein expression of ACE. TGF-β was also increased in aorta tissue of HF diet mice after 8 weeks. Altogether, we have observed that the HF diet-induced aortic stiffening may be associated with increased oxidative stress damage and activation of the RAS in vascular tissue.

Feeding high fibre diets changes luminal environment and morphology in the intestine of sows

DEFF Research Database (Denmark)

Serena, Anja; Hedemann, Mette Skou; Bach Knudsen, Knud Erik

2007-01-01

-products (sugar beet pulp, potato pulp, pectin residue, pea hull, brewer's spent grain, and seed residue). The diets were fed for a four-week period to 12 sows (4 for each diet). Sows were stunned 4 h post-feeding, and digesta and tissue samples were collected from various parts of the small and large intestines......Sows were fed three diets varying in type and level of dietary fibre (DF). The low fibre diet (LF; 17% DF) was based on wheat and barley. In the two high DF diets (HF1, high in soluble DF and HF2, high in insoluble DF;  44% DF), the cereal part of the diet was substituted with different co....... The carbohydrate load to the large intestine was 538-539 g/d when feeding the high DF diets and 190 g/d when feeding diet LF. Feeding sows the high DF diet containing large proportion of soluble DF resulted in a lower dry matter content of digesta (23 contra 28%), a higher tissue weight (2.9 contra 2.0 kg...

High-Fat and Fat-Enriched Diets Impair the Benefits of Moderate Physical Training in the Aorta and the Heart in Rats

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Cleverson Rodrigues Fernandes

2017-05-01

Full Text Available AimMillions of people die each year due to cardiovascular disease (CVD. A Western lifestyle not only fuses a significant intake of fat with physical inactivity and obesity but also promotes CVD. Recent evidence suggests that dietary fat intake impairs the benefits of physical training. We investigated whether aerobic training could reverse the adverse effects of a high-fat diet (HFD on the aorta. Then, we explored whether this type of exercise could reverse the damage to the heart that is imposed by fat-enriched diet (FED.MethodsRats were randomly assigned to two experiments, which lasted 8 weeks each. First, rats swam for 60 min and were fed either a regular diet [standard diet (STD] or an HFD. After aortic samples had been collected, the rats underwent a histopathological analysis for different biomarkers. Another experiment subjected rats that were fed either an STD or an FED to swimming for 20 or 90 min.ResultsThe first experiment revealed that rats that were subjected to an HFD-endured increased oxidative damage in the aorta that exercises could not counteract. Together with increased cyclooxygenase 2 expression, an HFD in combination with physical training increased the number of macrophages. A reduction in collagen fibers with an increased number of positive α-actin cells and expression of matrix metalloproteinase-2 occurred concomitantly. Upon analyzing the second experiment, we found that physically training rats that were given an FED for 90 min/day decreased the cardiac adipose tissue density, although it did not protect the heart from fat-induced oxidative damage. Even though the physical training lowered cholesterol levels that were promoted by the FED, the levels were still higher than those in the animals that were given an STD. Feeding rats an FED impaired the swimming protocol’s effects on lowering triglyceride concentration. Additionally, exercise was unable to reverse the fat-induced deregulation in hepatic

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

OpenAIRE

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

2017-01-01

Background The mother?s consumption of high-fat food can affect glucose metabolism and the hypothalamic?pituitary?adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Methods Female rats were randomly divided into normal and high-fat diet groups and were fed in a...

Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B

DEFF Research Database (Denmark)

Walz, Helena A; Härndahl, Linda; Wierup, Nils

2006-01-01

Inadequate islet adaptation to insulin resistance leads to glucose intolerance and type 2 diabetes. Here we investigate whether beta-cell cAMP is crucial for islet adaptation and prevention of glucose intolerance in mice. Mice with a beta-cell-specific, 2-fold overexpression of the c......AMP-degrading enzyme phosphodiesterase 3B (RIP-PDE3B/2 mice) were metabolically challenged with a high-fat diet. We found that RIP-PDE3B/2 mice early and rapidly develop glucose intolerance and insulin resistance, as compared with wild-type littermates, after 2 months of high-fat feeding. This was evident from...... did not reveal reduced insulin sensitivity in these tissues. Significant steatosis was noted in livers from high-fat-fed wild-type and RIP-PDE3B/2 mice and liver triacyl-glycerol content was 3-fold higher than in wild-type mice fed a control diet. Histochemical analysis revealed severe islet...

Dietary supplementation of organic selenium could improve performance, antibody response, and yolk oxidative stability in laying hens fed on diets containing oxidized fat.

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Laika, M; Jahanian, R

2015-06-01

The present study was carried out to investigate the effect of dietary supplementation of organic selenium (Se) on performance, egg quality indices, and yolk oxidative stability in laying hens fed diets with different fat sources. A total of 270 Hy-line W-36 Leghorn hens of 47 weeks of age were randomly distributed into the 5 replicate cages of 9 dietary treatments. Experimental diets consisted of a 3 × 3 factorial arrangement of treatments with three different fat sources (soybean oil, SO; yellow grease, YG; and palm fat powder, PFP) and three different levels of supplemental Se (0, 0.2, and 0.4 mg/kg of diet) as supplied by zinc-L-selenomethionine (ZnSeMet) complex, which fed during a 77-day feeding trial including 7 days for adaptation and 70 days as the main recording period. Results showed that the highest (P hens fed on SO-supplemented diets. Hen-day egg production was affected by both dietary fat source (P feed intake was not affected by experimental diets during the first 35-day period, dietary inclusion of PFP reduced feed intake during both second 35-day (P feed conversion ratio during the first 35-day period was assigned to the birds fed on SO-diets, followed by those fed YG-diets. Dietary supplementation of ZnSeMet improved (P feed efficiency during the first 35-day period. Supplementation of ZnSeMet into the diets increased yolk index, with more impact in hens fed on YG-diets. The highest concentration of yolk malondialdehyde was observed in YG-fed groups, and ZnSeMet supplementation of diets decreased (P hens fed on diets supplemented by YG, followed by those on SO-diets. Although different fat sources had no effect on antibody titer against Newcastle disease virus, supplemental ZnSeMet improved (P hens, with the highest impact in diets containing oxidized (high peroxide values) fat sources.

Effects of Shiitake Intake on Serum Lipids in Rats Fed Different High-Oil or High-Fat Diets.

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Asada, Norihiko; Kairiku, Rumi; Tobo, Mika; Ono, Akifumi

2018-04-27

Shiitake (Lentinula edodes) extract, eritadenine, has been shown to reduce cholesterol levels, and its hypocholesterolemic actions are involved in the metabolism of methionine. However, the mechanisms by which eritadenine affects cholesterol metabolism in animals fed a high-fat diet containing different sources of lipids have not yet been elucidated in detail. This study was conducted to investigate the effects of shiitake supplementation on serum lipid concentrations in rats fed a diet including a high amount of a plant oil (HO [high oil] and HOS [high oil with shiitake] groups), animal fat (HF [high fat] and HFS [high fat with shiitake] groups), or MCT- (medium-chain triglyceride-) rich plant oil (HM [high MCT] and HMS [high MCT with shiitake] groups). Rats in the HOS, HFS, and HMS groups were fed shiitake. When rats were fed a diet containing shiitake, serum triglyceride, cholesterol levels, and LCAT (lecithin-cholesterol acyltransferase) activities were lower in rats given MCT-rich plant oil than in those that consumed lard. The lipid type in the diet with shiitake also affected serum cholesterol levels and LCAT activities. The diet containing MCT-rich plant oil showed the greatest rates of decrease in all serum lipid profiles and LCAT activities. These results suggest that shiitake and MCT-rich plant oil work together to reduce lipid profiles and LCAT activity in serum.

Centrally administered urocortin 2 decreases gorging on high-fat diet in in both diet induced obesity-prone and -resistant rats

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Cottone, Pietro; Sabino, Valentina; Nagy, Tim R.; Coscina, Donald V.; Levin, Barry E.; Zorrilla, Eric P.

2013-01-01

Objective Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to play a role in obesity risk. The present study tested the hypothesis that i) the microstructure of chronic high-fat diet intake differs between genetically selected Diet-Induced Obesity (DIO) and Diet Resistant (DR) rats, and ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 (CRF2) agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats. Design Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 µg). Results Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 µg, suppressing high-fat diet intake by ~40% at the 3 µg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with 2/3rd less water. Conclusions Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically-prone DIO rats, which otherwise show a “gorging” meal pattern. These results open new opportunities of investigation towards treating some forms of diet-induced obesity. PMID:23478425

Synergistic effects of high fat feeding and apolipoprotein E deletion on enterocytic amyloid-beta abundance

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Dhaliwal Satvinder S

2008-04-01

Full Text Available Abstract Background Amyloid-β (Aβ, a key protein found in amyloid plaques of subjects with Alzheimer's disease is expressed in the absorptive epithelial cells of the small intestine. Ingestion of saturated fat significantly enhances enterocytic Aβ abundance whereas fasting abolishes expression. Apolipoprotein (apo E has been shown to directly modulate Aβ biogenesis in liver and neuronal cells but it's effect in enterocytes is not known. In addition, apo E modulates villi length, which may indirectly modulate Aβ as a consequence of differences in lipid absorption. This study compared Aβ abundance and villi length in wild-type (WT and apo E knockout (KO mice maintained on either a low-fat or high-fat diet. Wild-type C57BL/6J and apo E KO mice were randomised for six-months to a diet containing either 4% (w/w unsaturated fats, or chow comprising 16% saturated fats and 1% cholesterol. Quantitative immunohistochemistry was used to assess Aβ abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic Aβ abundance compared to WT controls. Results The saturated fat diet substantially increased enterocytic Aβ in WT and in apo E KO mice, however the effect was greater in the latter. Villi height was significantly greater in apo E KO mice than for WT controls when given the low-fat diet. However, WT mice had comparable villi length to apo E KO when fed the saturated fat and cholesterol enriched diet. There was no effect of the high-fat diet on villi length in apo E KO mice. Conclusion The findings of this study are consistent with the notion that lipid substrate availability modulates enterocytic Aβ. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.

High-fat diet-induced insulin resistance does not increase plasma anandamide levels or potentiate anandamide insulinotropic effect in isolated canine islets.

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Orison O Woolcott

Full Text Available Obesity has been associated with elevated plasma anandamide levels. In addition, anandamide has been shown to stimulate insulin secretion in vitro, suggesting that anandamide might be linked to hyperinsulinemia.To determine whether high-fat diet-induced insulin resistance increases anandamide levels and potentiates the insulinotropic effect of anandamide in isolated pancreatic islets.Dogs were fed a high-fat diet (n = 9 for 22 weeks. Abdominal fat depot was quantified by MRI. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp. Fasting plasma endocannabinoid levels were analyzed by liquid chromatography-mass spectrometry. All metabolic assessments were performed before and after fat diet regimen. At the end of the study, pancreatic islets were isolated prior to euthanasia to test the in vitro effect of anandamide on islet hormones. mRNA expression of cannabinoid receptors was determined in intact islets. The findings in vitro were compared with those from animals fed a control diet (n = 7.Prolonged fat feeding increased abdominal fat content by 81.3±21.6% (mean±S.E.M, P<0.01. In vivo insulin sensitivity decreased by 31.3±12.1% (P<0.05, concomitant with a decrease in plasma 2-arachidonoyl glycerol (from 39.1±5.2 to 15.7±2.0 nmol/L but not anandamide, oleoyl ethanolamide, linoleoyl ethanolamide, or palmitoyl ethanolamide. In control-diet animals (body weight: 28.8±1.0 kg, islets incubated with anandamide had a higher basal and glucose-stimulated insulin secretion as compared with no treatment. Islets from fat-fed animals (34.5±1.3 kg; P<0.05 versus control did not exhibit further potentiation of anandamide-induced insulin secretion as compared with control-diet animals. Glucagon but not somatostatin secretion in vitro was also increased in response to anandamide, but there was no difference between groups (P = 0.705. No differences in gene expression of CB1R or CB2R between groups were found.In canines, high-fat diet

Voluntary feed intake in rainbow trout is regulated by diet-induced differences in oxygen use.

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Saravanan, Subramanian; Geurden, Inge; Figueiredo-Silva, A Cláudia; Kaushik, Sadasivam; Verreth, Johan; Schrama, Johan W

2013-06-01

This study investigated the hypothesis that the voluntary feed intake in fish is regulated by diet-induced differences in oxygen use. Four diets were prepared with a similar digestible protein:digestible energy ratio (18 mg/kJ), but which differed in the composition of nonprotein energy source. This replacement of fat (F) by starch (S) was intended to create a diet-induced difference in oxygen use (per unit of feed): diets F30-S70, F50-S50, F65-S35, and F80-S20 with digestible fat providing 28, 49, 65, and 81% of the nonprotein digestible energy (NPDE), respectively. Each diet was fed to satiation to triplicate groups of 20 rainbow trout for 6 wk. As expected, diet-induced oxygen use decreased linearly (R(2) = 0.89; P digestible and metabolizable energy intakes of trout slightly increased with increasing NPDE as fat (i.e., decreasing starch content) (R(2) = 0.30, P = 0.08; and R(2) = 0.34, P = 0.05, respectively). Oxygen consumption of trout fed to satiation declined with increasing dietary NPDE as fat (R(2) = 0.48; P = 0.01). The inverse relation between digestible energy intake of trout and the diet-induced oxygen use (R(2) = 0.33; P = 0.05) suggests a possible role of diet-induced oxygen use in feed intake regulation as shown by the replacement of dietary fat by starch.

Exercise protects against high-fat diet-induced hypothalamic inflammation

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Yi, Chun-Xia; Al-Massadi, Omar; Donelan, Elizabeth; Lehti, Maarit; Weber, Jon; Ress, Chandler; Trivedi, Chitrang; Müller, Timo D.; Woods, Stephen C.; Hofmann, Susanna M.

2012-01-01

Hypothalamic inflammation is a potentially important process in the pathogenesis of high-fat diet-induced metabolic disorders that has recently received significant attention. Microglia are macrophage-like cells of the central nervous system which are activated by pro-inflammatory signals causing

Growth rate of sheep fed high fat ration

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Darwinsyah Lubis

1998-10-01

Full Text Available Incorporating high amount of fats into the ration for ruminants will affect the rumen microbes adversely and will reducefiber digestion potential. To correct such negative effects, the free fatty acids used for feed should be bond with Ca++, so it canpassing through the rumen savely (rumen by-pass fat. To test the Ca-fat utilization biologically, 20 growing male Garut shee pwere used and fed with 4 type of isocaloric-isoprotein concentrate feed which were allotted based on a randomized block desig nwith 5 replications. The concentrate (C-A was a positive control diet, while C-B was substituted with 10% free fatty acids (negative control, C-C was substituted with 10% Ca-fat, and C-D with 15% Ca-fat. The concentrate feed was fed at 500 g/d, while forage (King grass was 4 kg/d. Results of the experiment showed that the negative effect of free fatty acids can be corrected if it was given in the form of Ca-fat. Growth rate curve indicating a good growing pattern, with average daily gain was 100.18, 87.68, 112.86, and 115.00 g/d (P0.05. Carcass production was relatively good, where for C-A, C-B, C-C, and C-D were 14.84, 14.68, 16.34, and 15.72 kg (P<0.05 respectively, with final live weights of 34.00, 31.74, 34.58, and 34.30 kg (P<0.05. It can be concluded that Ca-fat (rumen by-pass fat can be used as an energy source component for growing sheep diet, and give the best result at 10% substitution rate in concentrate feed.

Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet

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Guohui eCai

2015-01-01

Full Text Available Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS. Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

Effects of angiotensin (1-7 on nephrosis of the mice with metabolic syndrome induced by high-salt and high-fat diet

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Nan ZHU

2013-11-01

Full Text Available Objective 　To establish a metabolic syndrome model of C57BL/6 mice by high-salt and high-fat diet, and investigate the effects of angiotensin converting enzyme 2 (ACE 2 and angiotensin (1-7 on renal damage in mice. Methods　Fifty-six male C57BL/6 mice were randomly divided into 7 groups (8 each, and fed with normal diet (0.3% NaCl, 10% fat, high-salt diet (8% NaCl, 10% fat, high-fat diet (0.3% NaCl, 60% fat, high-salt and high-fat diet (8% NaCl, 60% fat, high-salt and high-fat diet with enalapril 20mg/(kg•d, with valsartan 50mg/(kg•d, and with valsartan 50mg/(kg•d plus Mas receptor antagonist (A-779 150ng/(kg•d, respectively for 16 weeks. Basal metabolic index including blood pressure, body weight, blood glucose and urinary albumin excretion rate (UAER were tested. After intraperitoneal anesthesia with chloral hydrate, the blood was collected from the carotid artery. Serum angiotensin Ⅱ and angiotensin (1-7 levels were detected by ELISA; Western blotting was performed to evaluate the expression of ACE 2 protein and collagen Ⅲ in renal tissue; renal pathological changes were observed by HE and Masson staining. Results　The blood pressure, ratio of visceral fat weight/body weight, blood lipid, blood glucose and UAER increased significantly in the C57BL/6 mice fed with high-salt and high-fat diet for 16 weeks, and the renal fibrosis change was obvious, serum angiotensin Ⅱ level increased, expressions of ACE 2 and angiotensin (1-7 decreased significantly in the renal tissue. In different intervention groups, valsartan obviously alleviated the abnormal metabolism, ameliorated renal injury, promoted the expression of ACE2 and angiotensin (1-7 in the kidney and serum. However, no significant change was observed in the groups with intervention of enalapril or valsartan+A-779 compared with non-intervention group. Conclusions　High-salt and high-fat diet can be used to successfully establish the model of metabolic syndrome in C57BL/6

Exercise as a mean to reverse the detrimental effect of high-fat diet on bone’s fracture characteristics

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Ilias Doulamis

2017-04-01

Full Text Available The aim of this study is to investigate whether exercise can reverse some of the adverse effects of high-fat-diet-induced obesity on lipid metabolism and bone biomechanical properties. A total of 26 adult male C57bl/6J mice were randomly assigned into three groups: (A Control group (n=6, (B High-fat diet group (n=10, (C High-fat diet and exercise group (n=10. Body mass and relevant biochemical parameters were measured for the duration of the experimental protocol (37 weeks. Mechanical strength of both femurs of each animal was assessed in-vitro based on three point bending tests. It was re¬vealed that exposure to high-fat diet led to significant increase of body mass and cholesterol levels and also to substantial changes in bone mor-phology and strength. Ultimate stress for the animals exposed to high-fat diet and those exposed to high-fat-diet and exercise was 25% and 24% lower compared to control, respectively. Exercise increased bone thickness by 15% compared to animals that were not exposed to exer¬cise. It was concluded that high-fat-diet ap¬pears to have a detrimental effect on bone biomechanics and strength. Exer¬cise reversed the reduction in bone thickness that appears to be induced by high-fat diet. However no statistically significant increase in bone strength was observed.

High Caloric Diet for ALS Patients: High Fat, High Carbohydrate or High Protein

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Sarvin Sanaie

2015-01-01

Full Text Available ALS is a fatal motor neurodegenerative disease characterized by muscle atrophy and weakness, dysarthria, and dysphagia. The mean survival of ALS patients is three to five years, with 50% of those diagnosed dying within three years of onset (1. A multidisciplinary approach is crucial to set an appropriate plan for metabolic and nutritional support in ALS. Nutritional management incorporates a continuous assessment and implementation of dietary modifications throughout the duration of the disease. The nutritional and metabolic approaches to ALS should start when the diagnosis of ALS is made and should become an integral part of the continuous care to the patient, including nutritional surveillance, dietary counseling, management of dysphagia, and enteral nutrition when needed. Malnutrition and lean body mass loss are frequent findings in ALS patients necessitating comprehensive energy requirement assessment for these patients. Malnutrition is an independent prognostic factor for survival in ALS with a 7.7 fold increase in risk of death. Malnutrition is estimated to develop in one quarter to half of people with ALS (2. Adequate calorie and protein provision would diminish muscle loss in this vulnerable group of patients. Although appropriate amount of energy to be administered is yet to be established, high calorie diet is expected to be effective for potential improvement of survival; ALS patients do not normally receive adequate  intake of energy. A growing number of clinicians suspect that a high calorie diet implemented early in their disease may help people with ALS meet their increased energy needs and extend their survival. Certain high calorie supplements appear to be safe and well tolerated by people with ALS according to studies led by Universitäts klinikum Ulm's and, appear to stabilize body weight within 3 months. In a recent study by Wills et al., intake of high-carbohydrate low-fat supplements has been recommended in ALS patients (3

Effect of high-fat diet during gestation, lactation, or postweaning on physiological and behavioral indexes in borderline hypertensive rats.

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Mitra, Anaya; Alvers, Kristin M; Crump, Erica M; Rowland, Neil E

2009-01-01

Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high- or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or "junk food" diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance.

Mice long-term high-fat diet feeding recapitulates human cardiovascular alterations: an animal model to study the early phases of diabetic cardiomyopathy.

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Sebastián D Calligaris

Full Text Available BACKGROUND/AIM: Hypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as a pre-diabetic condition and recognized as an independent risk factor for cardiovascular diseases. To better understand the relationship between obesity, metabolic syndrome and cardiovascular disease as well as for the development of novel therapeutic strategies, animal models that reproduce the etiology, course and outcomes of these pathologies are required. The aim of this work was to characterize the long-term effects of high-fat diet-induced obesity on the mice cardiovascular system, in order to make available a new animal model for diabetic cardiomyopathy. METHODS/RESULTS: Male C57BL/6 mice were fed with a standardized high-fat diet (obese or regular diet (normal for 16 months. Metabolic syndrome was evaluated testing plasma glucose, triglycerides, cholesterol, insulin, and glucose tolerance. Arterial pressure was measured using a sphygmomanometer (non invasive method and by hemodynamic parameters (invasive method. Cardiac anatomy was described based on echocardiography and histological studies. Cardiac function was assessed by cardiac catheterization under a stress test. Cardiac remodelling and metabolic biomarkers were assessed by RT-qPCR and immunoblotting. As of month eight, the obese mice were overweight, hyperglycaemic, insulin resistant, hyperinsulinemic and hypercholesterolemic. At month 16, they also presented normal arterial pressure but altered vascular reactivity (vasoconstriction, and cardiac contractility reserve reduction, heart mass increase, cardiomyocyte hypertrophy, cardiac fibrosis, and heart metabolic compensations. By contrast, the normal mice remained healthy throughout the study. CONCLUSIONS: Mice fed with a high-fat diet for prolonged time recapitulates the etiology, course and outcomes of the early phases of human diabetic cardiomyopathy.

Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet.

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Sampey, Brante P; Vanhoose, Amanda M; Winfield, Helena M; Freemerman, Alex J; Muehlbauer, Michael J; Fueger, Patrick T; Newgard, Christopher B; Makowski, Liza

2011-06-01

Obesity has reached epidemic proportions worldwide and reports estimate that American children consume up to 25% of calories from snacks. Several animal models of obesity exist, but studies are lacking that compare high-fat diets (HFD) traditionally used in rodent models of diet-induced obesity (DIO) to diets consisting of food regularly consumed by humans, including high-salt, high-fat, low-fiber, energy dense foods such as cookies, chips, and processed meats. To investigate the obesogenic and inflammatory consequences of a cafeteria diet (CAF) compared to a lard-based 45% HFD in rodent models, male Wistar rats were fed HFD, CAF or chow control diets for 15 weeks. Body weight increased dramatically and remained significantly elevated in CAF-fed rats compared to all other diets. Glucose- and insulin-tolerance tests revealed that hyperinsulinemia, hyperglycemia, and glucose intolerance were exaggerated in the CAF-fed rats compared to controls and HFD-fed rats. It is well-established that macrophages infiltrate metabolic tissues at the onset of weight gain and directly contribute to inflammation, insulin resistance, and obesity. Although both high fat diets resulted in increased adiposity and hepatosteatosis, CAF-fed rats displayed remarkable inflammation in white fat, brown fat and liver compared to HFD and controls. In sum, the CAF provided a robust model of human metabolic syndrome compared to traditional lard-based HFD, creating a phenotype of exaggerated obesity with glucose intolerance and inflammation. This model provides a unique platform to study the biochemical, genomic and physiological mechanisms of obesity and obesity-related disease states that are pandemic in western civilization today.

Gamma delta T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice

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Gamma delta T cells are resident in adipose tissue and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5-10 week high milk fat diet. The high milk fat diet resulted in significant in...

Curcumin suppresses intestinal polyps in APC Min mice fed a high fat diet

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Christina Pettan-Brewer

2011-06-01

Full Text Available Colorectal cancer (CRC is a leading cause of cancer deaths in the United States. Various risk factors have been associated with CRC including increasing age and diet. Epidemiological and experimental studies have implicated a diet high in fat as an important risk factor for colon cancer. High fat diets can promote obesity resulting in insulin resistance and inflammation and the development of oxidative stress, increased cell proliferation, and suppression of apoptosis. Because of the high consumption of dietary fats, especially saturated fats, by Western countries, it is of interest to see if non-nutrient food factors might be effective in preventing or delaying CRC in the presence of high saturated fat intake. Curcumin (Curcuma longa, the main yellow pigment in turmeric, was selected to test because of its reported anti-tumor activity. APC Min mice, which develop intestinal polyps and have many molecular features of CRC, were fed a diet containing 35% pork fat, 33% sucrose, and a protein and vitamin mineral mixture (HFD with or without 0.5% curcumin. These cohorts were compared to APC Min mice receiving standard rodent chow (RC with 8% fat. APC Min mice fed the HFD for 3 months had a 23% increase in total number of polyps compared to APC Min mice on RC. Curcumin was able to significantly reverse the accelerated polyp development associated with the HFD suggesting it may be effective clinically in helping prevent colon cancer even when ingesting high amounts of fatty foods. The anti-tumor effect of curcumin was shown to be associated with enhanced apoptosis and increased efficiency of DNA repair. Since curcumin prevented the gain in body weight seen in APC Min mice ingesting the HFD, modulation of energy metabolism may also be a factor.

Odontella aurita-enriched diet prevents high fat diet-induced liver insulin resistance.

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Amine, Hamza; Benomar, Yacir; Haimeur, Adil; Messaouri, Hafida; Meskini, Nadia; Taouis, Mohammed

2016-01-01

The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways. © 2016 Society for Endocrinology.

Guarana (Paullinia cupana Stimulates Mitochondrial Biogenesis in Mice Fed High-Fat Diet

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Natália da Silva Lima

2018-01-01

Full Text Available The aim of this study was to evaluate the effects of guarana on mitochondrial biogenesis in a high-fat diet (HFD-fed mice. C57BL6J mice were divided in two groups: high-fat diet HFD and high-fat diet + guarana (HFD-GUA. Both groups received HFD and water ad libitum and the HFD-GUA group also received a daily gavage of guarana (1 g/kg weight. Body weight and food intake was measured weekly. Glycemic, triglyceride, and cholesterol levels were determined. VO2 and energy expenditure (EE were determined by indirect calorimetry. Gene expression was evaluated by real-time PCR and protein content by western blotting. The HFD-GUA group presented lower body weight, subcutaneous, retroperitoneal, visceral, and epididyimal adipose tissue depots, and glycemic and triglyceride levels, with no change in food intake and cholesterol levels. Furthermore, the HFD-GUA group presented an increase in VO2 and basal energy expenditure (EE, as well as Pgc1α, Creb1, Ampka1, Nrf1, Nrf2, and Sirt1 expression in the muscle and brown adipose tissue. In addition, the HFD-GUA group presented an increase in mtDNA (mitochondrial deoxyribonucleic acid content in the muscle when compared to the HFD group. Thus, our data showed that guarana leads to an increase in energetic metabolism and stimulates mitochondrial biogenesis, contributing to control of weight gain, even when associated with high-fat diet.

One-year high fat diet affects muscle-but not brain mitochondria

DEFF Research Database (Denmark)

Joergensen, Tenna; Grunnet, Niels; Quistorff, Bjørn

2015-01-01

It is well known that few weeks of high fat (HF) diet may induce metabolic disturbances and mitochondrial dysfunction in skeletalmuscle. However, little is known about the effects of long-term HF exposure and effects on brain mitochondria are unknown. Wistarrats were fed either chow (13E% fat......) or HF diet (60E% fat) for 1 year. The HF animals developed obesity, dyslipidemia, insulinresistance, and dysfunction of isolated skeletal muscle mitochondria: state 3 and state 4 were 30% to 50% increased (P .... Adding also succinate in state 3 resulted in ahigher substrate control ratio (SCR) with PC, but a lower SCR with pyruvate (P mitochondria from the same animal showed no changes with the substrates relevant...

Differential effects of restricted versus unlimited high-fat feeding in rats on fat mass, plasma hormones and brain appetite regulators.

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Shiraev, T; Chen, H; Morris, M J

2009-07-01

The rapid rise in obesity has been linked to altered food consumption patterns. There is increasing evidence that, in addition to total energy intake, the macronutrient composition of the diet may influence the development of obesity. The present study aimed to examine the impact of high dietary fat content, under both isocaloric and hypercaloric conditions, compared with a low fat diet, on adiposity, glucose and lipid metabolism, and brain appetite regulators in rats. Male Sprague-Dawley rats were exposed to one of three diets: control (14% fat), ad lib high-fat palatable (HFD, 35% fat) or high-fat palatable restricted (HFD-R, matched to the energy intake of control) and were killed in the fasting state 11 weeks later. Body weight was increased by 28% in unrestricted HFD fed rats, with an almost tripling of caloric intake and fat mass (P < 0.001) and double the plasma triglycerides of controls. Glucose intolerance and increased insulin levels were observed. HFD-R animals calorie matched to control had double their fat mass, plasma insulin and triglycerides (P < 0.05). Only ad lib consumption of the HFD increased the hypothalamic mRNA expression of the appetite-regulating peptides, neuropeptide Y and pro-opiomelanocortin. Although restricted consumption of palatable HFD had no significant impact on hypothalamic appetite regulators or body weight, it increased adiposity and circulating triglycerides, suggesting that the proportion of dietary fat, independent of caloric intake, affects fat deposition and the metabolic profile.

Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.

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Geng, Shanshan; Zhu, Weiwei; Xie, Chunfeng; Li, Xiaoting; Wu, Jieshu; Liang, Zhaofeng; Xie, Wei; Zhu, Jianyun; Huang, Cong; Zhu, Mingming; Wu, Rui; Zhong, Caiyun

2016-04-01

The aim of the present study was to investigate the in vivo effects of dietary medium-chain triglyceride (MCT) on inflammation and insulin resistance as well as the underlying potential molecular mechanisms in high fat diet-induced obese mice. Male C57BL/6J mice (n = 24) were fed one of the following three diets for a period of 12 weeks: (1) a modified AIN-76 diet with 5 % corn oil (normal diet); (2) a high-fat control diet (17 % w/w lard and 3 % w/w corn oil, HFC); (3) an isocaloric high-fat diet supplemented with MCT (17 % w/w MCT and 3 % w/w corn oil, HF-MCT). Glucose metabolism was evaluated by fasting blood glucose levels and intraperitoneal glucose tolerance test. Insulin sensitivity was evaluated by fasting serum insulin levels and the index of homeostasis model assessment-insulin resistance. The levels of serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α were measured by ELISA, and hepatic activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was determined using western blot analysis. Compared to HFC diet, consumption of HF-MCT did not induce body weight gain and white adipose tissue accumulation in mice. HFC-induced increases in serum fasting glucose and insulin levels as well as glucose intolerance were prevented by HF-MCT diet. Meanwhile, HF-MCT resulted in significantly lower serum IL-6 level and higher IL-10 level, and lower expression levels of inducible nitric oxide synthase and cyclooxygenase-2 protein in liver tissues when compared to HFC. In addition, HF-MCT attenuated HFC-triggered hepatic activation of NF-κB and p38 MAPK. Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.

Dietary whey proteins shield murine cecal microbiota from extensive disarray caused by a high-fat diet.

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Monteiro, Naice E S; Roquetto, Aline R; de Pace, Fernanda; Moura, Carolina S; Santos, Andrey Dos; Yamada, Aureo T; Saad, Mário José A; Amaya-Farfan, Jaime

2016-07-01

High-fat diets are used to induce adverse alterations in the intestinal microbiota, or dysbiosis, generalized inflammation and metabolic stress, which ultimately may lead to obesity. The influence of dietary whey proteins, whether intact or hydrolyzed, has been reported to improve glucose homeostasis and reduce stress. Therefore, the purpose of this work was to test if dietary milk-whey proteins, both in the intact form and hydrolyzed, could have an effect on the compositional changes of the cecal microbiota that can be induced in mice when receiving a high-fat diet in combination with the standard casein. Male C57BL/6 mice were fed a control casein diet (AIN 93-G); high-fat-casein (HFCAS); high-fat-whey protein concentrate (HFWPC) and high-fat whey-protein hydrolysate (HFWPH) for 9weeks. The intestinal microbiota composition was analyzed by 16S-rRNA of the invariant (V1-V3) gene, potentially endotoxemic lipopolysaccharide (LPS) release was determined colorimetrically, and liver fat infiltration assessed by light microscopy. The high-fat diet proved to induce dysbiosis in the animals by inverting the dominance of the phylum Firmicutes over Bacteroidetes, promoted the increase of LPS and resulted in liver fat infiltration. The whey proteins, whether intact or hydrolyzed, resisted the installation of dysbiosis, prevented the surge of circulating LPS and prevented fat infiltration in the liver. It is concluded that dietary whey proteins exert metabolic actions that tend to preserve the normal microbiota profile, while mitigating liver fat deposition in mice consuming a high-fat diet for nine weeks. Such beneficial effects were not seen when casein was the dietary protein. The hydrolyzed whey protein still differed from the normal whey protein by selectively protecting the Bacteroidetes phylum. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ginger extract and aerobic training reduces lipid profile in high-fat fed diet rats.

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Khosravani, M; Azarbayjani, M A; Abolmaesoomi, M; Yusof, A; Zainal Abidin, N; Rahimi, E; Feizolahi, F; Akbari, M; Seyedjalali, S; Dehghan, F

2016-04-01

Obesity, hyperglycemia and dyslipidemia, are major risk factors. However, natural therapies, dietary components, and physical activity may effect on these concerns. The aim of this study was to examine the effect of aerobic exercise and consumption of liquid ginger extract on lipid profile of Male rats with a high-fat fed diet. 32 rats were randomly divided into 4 groups: 1) aerobic exercise, 2) Ginger extract, 3) combined aerobic exercise and Ginger extract, and 4) the control. Subjects of the first three groups received ginger extract via gavage feeding of 250 mg/kg. The exercise program was 3 sessions per week on 3 different days over 4 weeks. Total cholesterol (TC), Triglyceride (TG), HDL and LDL were measured 24-h before the first session and 24-h after the final training session. The concentration of TG in the control group was significantly higher than other groups. In addition, the mean concentration of TG in the aerobic exercise group was significantly lower than Ginger extract group but there was no significant difference as compared to combined aerobic exercise and ginger extract group. The combination of aerobic exercise and ginger consumption significantly reduced the TG level compared to ginger group. TC and LDL concentrations were significantly decreased in all groups compare to control. The combination of aerobic exercise and ginger extract feeding caused a significant increase in HDL levels. The finding of this study suggests that the combination of aerobic exercise and liquid ginger extract consumption might be an effective method of reducing lipid profiles, which will reduce the risk of cardiovascular diseases caused by high-fat diets.

Post-weaning high-fat diet results in growth cartilage lesions in young male rats.

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Samuel S Haysom

Full Text Available To determine if a high-fat diet (HF from weaning would result in a pro-inflammatory state and affect joint cartilage, we fed male rats either HF or Chow diet post-weaning, and voluntary wheel exercise (EX or cage only activity (SED after 9 weeks of age. At 17 weeks body composition, plasma biomarkers and histomorphology scores of femoro-tibial cartilages of HF-SED, HF-EX, Chow-SED and Chow-EX groups were compared. Food intake and activity were not significantly different between groups. HF diet resulted in significantly higher weight gain, %fat, fat:lean ratio, and plasma leptin, insulin and TNFα concentrations, with significant interactions between diet and exercise. No abnormal features were detected in the hyaline articular cartilage or in the metaphyseal growth plate in all four groups. However, collagen type X- positive regions of retained epiphyseal growth cartilage (EGC was present in all HF-fed animals and significantly greater than that observed in Chow-fed sedentary rats. Most lesions were located in the lateral posterior aspect of the tibia and/or femur. The severity of lesions was greater in HF-fed animals. Although exercise had a significantly greater effect in reducing adiposity and associated systemic inflammation in HF-fed rats, it had no effect on lesion incidence or severity. Lesion incidence was also significantly associated with indices of obesity and plasma markers of chronic inflammation. Clinically, EGC lesions induced by HF feeding in rats from very early in life, and possibly by insufficient activity, is typical of osteochondrosis in animals. Such lesions may be the precursor of juvenile osteochondritis dissecans requiring surgery in children/adolescents, conservative management of which could benefit from improved understanding of early changes in cellular and gene expression.

Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet-Induced Diabetic Retinopathy.

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Rajagopal, Rithwick; Bligard, Gregory W; Zhang, Sheng; Yin, Li; Lukasiewicz, Peter; Semenkovich, Clay F

2016-04-01

Obesity predisposes to human type 2 diabetes, the most common cause of diabetic retinopathy. To determine if high-fat diet-induced diabetes in mice can model retinal disease, we weaned mice to chow or a high-fat diet and tested the hypothesis that diet-induced metabolic disease promotes retinopathy. Compared with controls, mice fed a diet providing 42% of energy as fat developed obesity-related glucose intolerance by 6 months. There was no evidence of microvascular disease until 12 months, when trypsin digests and dye leakage assays showed high fat-fed mice had greater atrophic capillaries, pericyte ghosts, and permeability than controls. However, electroretinographic dysfunction began at 6 months in high fat-fed mice, manifested by increased latencies and reduced amplitudes of oscillatory potentials compared with controls. These electroretinographic abnormalities were correlated with glucose intolerance. Unexpectedly, retinas from high fat-fed mice manifested striking induction of stress kinase and neural inflammasome activation at 3 months, before the development of systemic glucose intolerance, electroretinographic defects, or microvascular disease. These results suggest that retinal disease in the diabetic milieu may progress through inflammatory and neuroretinal stages long before the development of vascular lesions representing the classic hallmark of diabetic retinopathy, establishing a model for assessing novel interventions to treat eye disease. © 2016 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.

A Difference in Fatty Acid Composition of Isocaloric High-Fat Diets Alters Metabolic Flexibility in Male C57BL/6JOlaHsd Mice.

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Loes P M Duivenvoorde

Full Text Available Poly-unsaturated fatty acids (PUFAs are considered to be healthier than saturated fatty acids (SFAs, but others postulate that especially the ratio of omega-6 to omega-3 PUFAs (n6/n3 ratio determines health. Health can be determined with biomarkers, but functional health status is likely better reflected by challenge tests that assess metabolic flexibility. The aim of this study was to determine the effect of high-fat diets with different fatty acid compositions, but similar n6/n3 ratio, on metabolic flexibility. Therefore, adult male mice received isocaloric high-fat diets with either predominantly PUFAs (HFpu diet or predominantly SFAs (HFs diet but similar n6/n3 ratio for six months, during and after which several biomarkers for health were measured. Metabolic flexibility was assessed by the response to an oral glucose tolerance test, a fasting and re-feeding test and an oxygen restriction test (OxR; normobaric hypoxia. The latter two are non-invasive, indirect calorimetry-based tests that measure the adaptive capacity of the body as a whole. We found that the HFs diet, compared to the HFpu diet, increased mean adipocyte size, liver damage, and ectopic lipid storage in liver and muscle; although, we did not find differences in body weight, total adiposity, adipose tissue health, serum adipokines, whole body energy balance, or circadian rhythm between HFs and HFpu mice. HFs mice were, furthermore, less flexible in their response to both fasting- re-feeding and OxR, while glucose tolerance was indistinguishable. To conclude, the HFs versus the HFpu diet increased ectopic fat storage, liver damage, and mean adipocyte size and reduced metabolic flexibility in male mice. This study underscores the physiological relevance of indirect calorimetry-based challenge tests.

A low-carbohydrate/high-fat diet improves glucoregulation in type 2 diabetes mellitus by reducing postabsorptive glycogenolysis.

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Allick, Gideon; Bisschop, Peter H; Ackermans, Mariette T; Endert, Erik; Meijer, Alfred J; Kuipers, Folkert; Sauerwein, Hans P; Romijn, Johannes A

2004-12-01

The aim of this study was to examine the mechanisms by which dietary carbohydrate and fat modulate fasting glycemia. We compared the effects of an eucaloric high-carbohydrate (89% carbohydrate) and high-fat (89% fat) diet on fasting glucose metabolism and insulin sensitivity in seven obese patients with type 2 diabetes using stable isotopes and euglycemic hyperinsulinemic clamps. At basal insulin levels glucose concentrations were 148 +/- 11 and 123 +/- 11 mg/dl (8.2 +/- 0.6 and 6.8 +/- 0.6 mmol/liter) on the high-carbohydrate and high-fat diet, respectively (P carbohydrate diet (1.88 +/- 0.06 vs. 1.55 +/- 0.05 mg/kg.min (10.44 +/- 0.33 vs. 8.61 +/- 0.28 micromol/kg.min) (P carbohydrate and high-fat diet, respectively. We conclude that short-term variations in dietary carbohydrate to fat ratios affect basal glucose metabolism in people with type 2 diabetes merely through modulation of the rate of glycogenolysis, without affecting insulin sensitivity of glucose metabolism.

TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice.

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Stephen J Kentish

Full Text Available Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1 are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice.TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined.Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet.TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity.

Anti-oxidant and anti-hyperlipidemic activity of Hemidesmus indicus in rats fed with high-fat diet

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Suganya Venkateshan

2016-08-01

Full Text Available Objective: Dietary changes playmajor risk roles in oxidative stress andcardiovascular disease and modulate normal metabolic function. The present study was designed to investigate the ameliorative potential of different extracts of Hemidesmus indicus to experimental high-fat diet in wistar rats, and their possible mechanism of action.  Materials and Methods: Male wistar rats were divided into 6 groups (n=6/group andfed with a standard diet (control, high-fat diet (HFD, high-fat diet supplemented with different extracts and positive control for 9 weeks. High-fat diet induced changes in average body weight andoxidative stress and elevated levels of plasma lipid profilein rats. Results: Oral administration of methanolic extract of H. indicus(200 mg/kg offered a significant dose-dependent protection against HFD-induced oxidative stress, as reflected in the levels of catalase (pConclusion: The present study revealed that the methanolic extract of H.indicus protects against oxidative stress, hyperlipidemia and liver damage.

Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat

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Hidalgo, Juan; Florit, Sergi; Giralt, Mercedes

2010-01-01

Interleukin-6 (IL-6) is a major cytokine involved in both normal physiological brain functions and underlying significant neuropathology. IL-6 has been suggested to play a role in the control of body weight but the results are somewhat controversial. In this study we have challenged transgenic mice...... with astrocyte-targeted IL-6 expression (GFAP-IL6 mice) with a high-fat diet (55% kcal from fat) versus a control diet (10%). The results demonstrate that the GFAP-IL6 mice are resistant to high-fat diet-induced increases in body weight and body fat, apparently without altering food intake and with no evidences...... of increased sympathetic tone. The high-fat diet-induced impaired responses to an insulin tolerance test (ITT), and to an oral glucose tolerance test (OGTT) in both genotypes. The GFAP-IL6 mice did not differ from littermate wild-type (WT) mice in ITT, but they were more glucose intolerant following the high...

Alternate-Day High-Fat Diet Induces an Increase in Mitochondrial Enzyme Activities and Protein Content in Rat Skeletal Muscle.

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Li, Xi; Higashida, Kazuhiko; Kawamura, Takuji; Higuchi, Mitsuru

2016-04-06

Long-term high-fat diet increases muscle mitochondrial enzyme activity and endurance performance. However, excessive calorie intake causes intra-abdominal fat accumulation and metabolic syndrome. The purpose of this study was to investigate the effect of an alternating day high-fat diet on muscle mitochondrial enzyme activities, protein content, and intra-abdominal fat mass in rats. Male Wistar rats were given a standard chow diet (CON), high-fat diet (HFD), or alternate-day high-fat diet (ALT) for 4 weeks. Rats in the ALT group were fed a high-fat diet and standard chow every other day for 4 weeks. After the dietary intervention, mitochondrial enzyme activities and protein content in skeletal muscle were measured. Although body weight did not differ among groups, the epididymal fat mass in the HFD group was higher than those of the CON and ALT groups. Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activities in the plantaris muscle of rats in HFD and ALT were significantly higher than that in CON rats, whereas there was no difference between HFD and ALT groups. No significant difference was observed in muscle glycogen concentration or glucose transporter-4 protein content among the three groups. These results suggest that an alternate-day high-fat diet induces increases in mitochondrial enzyme activities and protein content in rat skeletal muscle without intra-abdominal fat accumulation.

Analysis of time-dependent adaptations in whole-body energy balance in obesity induced by high-fat diet in rats

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Maghdoori Babak

2011-06-01

Full Text Available Abstract Background High-fat (HF diet has been extensively used as a model to study metabolic disorders of human obesity in rodents. However, the adaptive whole-body metabolic responses that drive the development of obesity with chronically feeding a HF diet are not fully understood. Therefore, this study investigated the physiological mechanisms by which whole-body energy balance and substrate partitioning are adjusted in the course of HF diet-induced obesity. Methods Male Wistar rats were fed ad libitum either a standard or a HF diet for 8 weeks. Food intake (FI and body weight were monitored daily, while oxygen consumption, respiratory exchange ratio, physical activity, and energy expenditure (EE were assessed weekly. At week 8, fat mass and lean body mass (LBM, fatty acid oxidation and uncoupling protein-1 (UCP-1 content in brown adipose tissue (BAT, as well as acetyl-CoA carboxylase (ACC content in liver and epidydimal fat were measured. Results Within 1 week of ad libitum HF diet, rats were able to spontaneously reduce FI to precisely match energy intake of control rats, indicating that alterations in dietary energy density were rapidly detected and FI was self-regulated accordingly. Oxygen consumption was higher in HF than controls throughout the study as whole-body fat oxidation also progressively increased. In HF rats, EE initially increased, but then reduced as dark cycle ambulatory activity reached values ~38% lower than controls. No differences in LBM were detected; however, epidydimal, inguinal, and retroperitoneal fat pads were 1.85-, 1.89-, and 2.54-fold larger in HF-fed than control rats, respectively. Plasma leptin was higher in HF rats than controls throughout the study, indicating the induction of leptin resistance by HF diet. At week 8, UCP-1 content and palmitate oxidation in BAT were 3.1- and 1.5-fold higher in HF rats than controls, respectively, while ACC content in liver and epididymal fat was markedly reduced

The effects of high-fat diet, branched-chain amino acids and exercise on female C57BL/6 mouse Achilles tendon biomechanical properties

OpenAIRE

Boivin, G. P.; Platt, K. M.; Corbett, J.; Reeves, J.; Hardy, A. L.; Elenes, E. Y.; Charnigo, R. J.; Hunter, S. A.; Pearson, K. J.

2013-01-01

Objectives The goals of this study were: 1) to determine if high-fat diet (HFD) feeding in female mice would negatively impact biomechanical and histologic consequences on the Achilles tendon and quadriceps muscle; and 2) to investigate whether exercise and branched-chain amino acid (BCAA) supplementation would affect these parameters or attenuate any negative consequences resulting from HFD consumption. Methods We examined the effects of 16 weeks of 60% HFD feeding, voluntary exercise (free ...

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

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Kathleen M Botham

2012-02-01

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

A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance

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Bosse, John D.; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E. Dale; Pereira, Troy J.; Dolinsky, Vernon W.; Symons, J. David; Jalili, Thunder

2013-01-01

Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-...

Fish Oil Ameliorates High-Fat Diet Induced Male Mouse Reproductive Dysfunction via Modifying the Rhythmic Expression of Testosterone Synthesis Related Genes

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Hualin Wang

2018-04-01

Full Text Available The present study aims to investigate the protective effects of ω-3 polyunsaturated fatty acids (ω-3PUFAs against high-fat diet induced male mouse reproductive dysfunction and to explore circadian regulation mechanisms. Male C57BL/6 mice were randomly divided into three groups and fed a normal chow diet (control group, CON, a high-fat diet (HFD group or a HFD supplemented with fish oil (FO group for 12 weeks. After 12 weeks of feeding, the body weight and the ratio of perinephric and epididymal fat weight to body weight were significantly higher in the HFD group compared with the CON group. The supplement of fish oil rich in ω-3PUFAs only slightly reduced the HFD-induced obesity but remarkably ameliorated HFD-induced dyslipidemia, sexual hormones disorder, testicle lesions and germ cell apoptosis. Fish oil supplementation restored the expression of steroid synthesis associated genes in HFD fed mouse and flattened the HFD-induced oscillations in circadian genes’ expression. Fish oil supplementation prevented HFD-induced male mouse reproductive dysfunction and modified the rhythmic expression of testosterone synthesis related genes.

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

International Nuclear Information System (INIS)

Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

2012-01-01

Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver. �

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

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Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D., E-mail: cklaasse@kumc.edu

2012-11-01

Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver. �

BL153 Partially Prevents High-Fat Diet Induced Liver Damage Probably via Inhibition of Lipid Accumulation, Inflammation, and Oxidative Stress

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Jian Wang

2014-01-01

Full Text Available The present study was to investigate whether a magnolia extract, named BL153, can prevent obesity-induced liver damage and identify the possible protective mechanism. To this end, obese mice were induced by feeding with high fat diet (HFD, 60% kcal as fat and the age-matched control mice were fed with control diet (10% kcal as fat for 6 months. Simultaneously these mice were treated with or without BL153 daily at 3 dose levels (2.5, 5, and 10 mg/kg by gavage. HFD feeding significantly increased the body weight and the liver weight. Administration of BL153 significantly reduced the liver weight but without effects on body weight. As a critical step of the development of NAFLD, hepatic fibrosis was induced in the mice fed with HFD, shown by upregulating the expression of connective tissue growth factor and transforming growth factor beta 1, which were significantly attenuated by BL153 in a dose-dependent manner. Mechanism study revealed that BL153 significantly suppressed HFD induced hepatic lipid accumulation and oxidative stress and slightly prevented liver inflammation. These results suggest that HFD induced fibrosis in the liver can be prevented partially by BL153, probably due to reduction of hepatic lipid accumulation, inflammation and oxidative stress.

Effects of High Fat Diet and Physical Exercise on Glucose Tolelance and Insulin Sensitivity in Rats

OpenAIRE

福田,哲也

1987-01-01

To investigate the interrelationships between the westernized diet and physical exercise as they affect the development of non-insulin-dependent diabetes mellitus (NIDDM), adiposity, glucose tolerance and insulin response to an intraperitoneal glucose load (1.5g/kg bw) and insulin sensitivity to exogenous insulin (0.2U/kg bw) were studied in spontaneously exercised and sedentary rats fed either a high fat diet (40% fat, modern western type) or a low fat diet (10% fat, traditional Japanese typ...

Protein carbonylation associated to high-fat, high-sucrose diet and its metabolic effects.

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Méndez, Lucía; Pazos, Manuel; Molinar-Toribio, Eunice; Sánchez-Martos, Vanesa; Gallardo, José M; Rosa Nogués, M; Torres, Josep L; Medina, Isabel

2014-12-01

The present research draws a map of the characteristic carbonylation of proteins in rats fed high-caloric diets with the aim of providing a new insight of the pathogenesis of metabolic diseases derived from the high consumption of fat and refined carbohydrates. Protein carbonylation was analyzed in plasma, liver and skeletal muscle of Sprague-Dawley rats fed a high-fat, high-sucrose (HFHS) diet by a proteomics approach based on carbonyl-specific fluorescence-labeling, gel electrophoresis and mass spectrometry. Oxidized proteins along with specific sites of oxidative damage were identified and discussed to illustrate the consequences of protein oxidation. The results indicated that long-term HFHS consumption increased protein oxidation in plasma and liver; meanwhile, protein carbonyls from skeletal muscle did not change. The increment of carbonylation by HFHS diet was singularly selective on specific target proteins: albumin from plasma and liver, and hepatic proteins such as mitochondrial carbamoyl-phosphate synthase (ammonia), mitochondrial aldehyde dehydrogenase, argininosuccinate synthetase, regucalcin, mitochondrial adenosine triphosphate synthase subunit beta, actin cytoplasmic 1 and mitochondrial glutamate dehydrogenase 1. The possible consequences that these specific protein carbonylations have on the excessive weight gain, insulin resistance and nonalcoholic fatty liver disease resulting from HFHS diet consumption are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypolipidemic, antioxidant and antiatherogenic property of sardine by-products proteins in high-fat diet induced obese rats.

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Affane, Fouad; Louala, Sabrine; El Imane Harrat, Nour; Bensalah, Fatima; Chekkal, Hadjera; Allaoui, Amine; Lamri-Senhadji, Myriem

2018-04-15

Fish by-products valorization on account of their richness in bioactive compounds may represent a better alternative to marine products with a view to economic profitability and sustainable development. In this study, we compared the effect of sardine by-product proteins (SBy-P), with those of the fillets (SF-P) or casein (Cas), on growth parameters, serum leptin level, lipids disorders, lipid peroxidation and reverse cholesterol transport, in diet-induced obese rats. Obesity was induced by feeding rats a high-fat diet (20% sheep fat), during 12 weeks. At body weight (BW) of 400 ± 20 g, eighteen obese rats were divided into three homogenous groups and continue to consume the high-fat diet for 4 weeks containing either, 20% SBy-P, SF-P or Cas. The results showed that SBy-P, compared to SF-P and Cas, efficiently reduced food intake (FI), BW gain and serum leptin level, and improved blood lipids levels and reverse cholesterol transport by reducing total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-HDL 1 -C) serum levels, increasing the level of high-density lipoprotein cholesterol (HDL 2 -C and HDL 3 -C), and enhancing lecithin: cholesterol acyltransferase (LCAT) activity. Furthermore, they attenuated lipid peroxidation by increasing atheroprotective activity of the paraoxonase-1 (PON-1). Sardine by-product proteins due to their richness in certain essential amino acids, highlight weight-loss, lipid-lowering, antioxidant and anti-atherogenic potentials, contributing to the improvement of the complications associated with obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

Dietary fat and gut microbiota interactions determine diet-induced obesity in mice.

Science.gov (United States)

Kübeck, Raphaela; Bonet-Ripoll, Catalina; Hoffmann, Christina; Walker, Alesia; Müller, Veronika Maria; Schüppel, Valentina Luise; Lagkouvardos, Ilias; Scholz, Birgit; Engel, Karl-Heinz; Daniel, Hannelore; Schmitt-Kopplin, Philippe; Haller, Dirk; Clavel, Thomas; Klingenspor, Martin

2016-12-01

Gut microbiota may promote positive energy balance; however, germfree mice can be either resistant or susceptible to diet-induced obesity (DIO) depending on the type of dietary intervention. We here sought to identify the dietary constituents that determine the susceptibility to body fat accretion in germfree (GF) mice. GF and specific pathogen free (SPF) male C57BL/6N mice were fed high-fat diets either based on lard or palm oil for 4 wks. Mice were metabolically characterized at the end of the feeding trial. FT-ICR-MS and UPLC-TOF-MS were used for cecal as well as hepatic metabolite profiling and cecal bile acids quantification, respectively. Hepatic gene expression was examined by qRT-PCR and cecal gut microbiota of SPF mice was analyzed by high-throughput 16S rRNA gene sequencing. GF mice, but not SPF mice, were completely DIO resistant when fed a cholesterol-rich lard-based high-fat diet, whereas on a cholesterol-free palm oil-based high-fat diet, DIO was independent of gut microbiota. In GF lard-fed mice, DIO resistance was conveyed by increased energy expenditure, preferential carbohydrate oxidation, and increased fecal fat and energy excretion. Cecal metabolite profiling revealed a shift in bile acid and steroid metabolites in these lean mice, with a significant rise in 17β-estradiol, which is known to stimulate energy expenditure and interfere with bile acid metabolism. Decreased cecal bile acid levels were associated with decreased hepatic expression of genes involved in bile acid synthesis. These metabolic adaptations were largely attenuated in GF mice fed the palm-oil based high-fat diet. We propose that an interaction of gut microbiota and cholesterol metabolism is essential for fat accretion in normal SPF mice fed cholesterol-rich lard as the main dietary fat source. This is supported by a positive correlation between bile acid levels and specific bacteria of the order Clostridiales (phylum Firmicutes ) as a characteristic feature of normal SPF mice

Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet

OpenAIRE

Ma, Xiaoqing; Du, Wenhua; Shao, Shanshan; Yu, Chunxiao; Zhou, Lingyan; Jing, Fei

2018-01-01

Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission el...

Differential Effects of High-Carbohydrate and High-Fat Diet Composition on Metabolic Control and Insulin Resistance in Normal Rats

Science.gov (United States)

Ble-Castillo, Jorge L.; Aparicio-Trapala, María A.; Juárez-Rojop, Isela E.; Torres-Lopez, Jorge E.; Mendez, Jose D.; Aguilar-Mariscal, Hidemi; Olvera-Hernández, Viridiana; Palma-Cordova, Leydi C.; Diaz-Zagoya, Juan C.

2012-01-01

The macronutrient component of diets is critical for metabolic control and insulin action. The aim of this study was to compare the effects of high fat diets (HFDs) vs. high carbohydrate diets (HCDs) on metabolic control and insulin resistance in Wistar rats. Thirty animals divided into five groups (n = 6) were fed: (1) Control diet (CD); (2) High-saturated fat diet (HSFD); (3) High-unsaturated fat diet (HUFD); (4) High-digestible starch diet, (HDSD); and (5) High-resistant starch diet (HRSD) during eight weeks. HFDs and HCDs reduced weight gain in comparison with CD, however no statistical significance was reached. Calorie intake was similar in both HFDs and CD, but rats receiving HCDs showed higher calorie consumption than other groups, (p < 0.01). HRSD showed the lowest levels of serum and hepatic lipids. The HUFD induced the lowest fasting glycemia levels and HOMA-IR values. The HDSD group exhibited the highest insulin resistance and hepatic cholesterol content. In conclusion, HUFD exhibited the most beneficial effects on glycemic control meanwhile HRSD induced the highest reduction on lipid content and did not modify insulin sensitivity. In both groups, HFDs and HCDs, the diet constituents were more important factors than caloric intake for metabolic disturbance and insulin resistance. PMID:22754464

Liver Fat Scores Moderately Reflect Interventional Changes in Liver Fat Content by a Low-Fat Diet but Not by a Low-Carb Diet.

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Kabisch, Stefan; Bäther, Sabrina; Dambeck, Ulrike; Kemper, Margrit; Gerbracht, Christiana; Honsek, Caroline; Sachno, Anna; Pfeiffer, Andreas F H

2018-01-31

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder all over the world, mainly being associated with a sedentary lifestyle, adiposity, and nutrient imbalance. The increasing prevalence of NAFLD accommodates similar developments for type 2 diabetes and diabetes-related comorbidities and complications. Therefore, early detection of NAFLD is an utmost necessity. Potentially helpful tools for the prediction of NAFLD are liver fat indices. The fatty liver index (FLI) and the NAFLD-liver fat score (NAFLD-LFS) have been recently introduced for this aim. However, both indices have been shown to correlate with liver fat status, but there is neither sufficient data on the longitudinal representation of liver fat change, nor proof of a diet-independent correlation between actual liver fat change and change of index values. While few data sets on low-fat diets have been published recently, low-carb diets have not been yet assessed in this context. We aim to provide such data from a highly effective short-term intervention to reduce liver fat, comparing a low-fat and a low-carb diet in subjects with prediabetes. Anthropometric measurements, magnetic resonance (MR)-based intrahepatic lipid (IHL) content, and several serum markers for liver damage have been collected in 140 subjects, completing the diet phase in this trial. Area-under-the-responder-operator-curves (AUROC) calculations as well as cross-sectional and longitudinal Spearman correlations were used. Both FLI and NAFLD-LFS predict liver fat with moderate accuracy at baseline (AUROC 0.775-0.786). These results are supported by correlation analyses. Changes in liver fat, achieved by the dietary intervention, correlate moderately with changes in FLI and NAFLD-LFS in the low-fat diet, but not in the low-carb diet. A correlation analysis between change of actual IHL content and change of single elements of the liver fat indices revealed diet-specific moderate to strong correlations between ΔIHL and

Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance

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Madsen, Lise; Guerre-Millo, Michéle; Flindt, Esben N

2002-01-01

Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis. Here we evaluate the ability of TTA to prevent diet-induced and genetically determined adiposity and insulin resistance. In Wistar rats fed a high fat diet, TTA administration...... completely prevented diet-induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa) rats TTA treatment reduced the epididymal adipose tissue mass and improved insulin sensitivity. All three rodent peroxisome proliferator-activated receptor (PPAR) subtypes were activated by TTA...... that a TTA-induced increase in hepatic fatty acid oxidation and ketogenesis drains fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects of TTA on fat mass accumulation and peripheral insulin sensitivity....

Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

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Kanno, Ayumi, E-mail: akanno@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Asahara, Shun-ichiro, E-mail: asahara@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Masuda, Katsuhisa, E-mail: katsuhisa.m.0707@gmail.com [Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142 (Japan); Matsuda, Tomokazu, E-mail: tomokazu@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Kimura-Koyanagi, Maki, E-mail: koyanagi@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Seino, Susumu, E-mail: seino@med.kobe-u.ac.jp [Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047 (Japan); Ogawa, Wataru, E-mail: ogawa@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Kido, Yoshiaki, E-mail: kido@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142 (Japan)

2015-03-13

A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets.

Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

International Nuclear Information System (INIS)

Kanno, Ayumi; Asahara, Shun-ichiro; Masuda, Katsuhisa; Matsuda, Tomokazu; Kimura-Koyanagi, Maki; Seino, Susumu; Ogawa, Wataru; Kido, Yoshiaki

2015-01-01

A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets

Cardiac Hypertrophy and Brain Natriuretic Peptide Levels in an Ovariectomized Rat Model Fed a High-Fat Diet

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Goncalves, Gleisy Kelly; de Oliveira, Thiago Henrique Caldeira; de Oliveira Belo, Najara

2017-01-01

Background Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims of this study were to assess cardiac hypertrophy and BNP levels in ovariectomized rats fed a high-fat diet. Material/Methods Forty-eight female Wistar rats were divided into four groups: sham-operated rats fed a control diet (SC) (n=12); ovariectomized rats fed a control diet (OC) (n=12); sham-operated rats fed a high-fat diet (SF) (n=12); and ovariectomized rats fed a high-fat diet (OF) (n=12). Body weight and blood pressure were measured weekly for 24 weeks. Rats were then euthanized, and plasma samples and heart tissue were studied for gene expression, hydroxyproline levels, and histological examination. Results A high-fat diet and ovariectomy (group OF) increased the weight body and the systolic blood pressure after three months and five months, respectively. Cardiomyocyte hypertrophy was associated with increased expression of ventricular BNP, decreased natriuretic peptide receptor (NPR)-A and increased levels of hydroxyproline and transforming growth factor (TGF)-β. The plasma levels of BNP and estradiol were inversely correlated; expression of estrogen receptor (ER)β and ERα were reduced. Conclusions The findings of this study showed that, in the ovariectomized rats fed a high-fat diet, the BNP-NPR-A receptor complex was involved in cardiac remodeling. BNP may be a marker of cardiac hypertrophy in this animal model. PMID:29249795

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

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Stephanie A. Segovia

2018-03-01

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

Body fat accumulation in zebrafish is induced by a diet rich in fat and reduced by supplementation with green tea extract.

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Shinichi Meguro

Full Text Available Fat-rich diets not only induce obesity in humans but also make animals obese. Therefore, animals that accumulate body fat in response to a high-fat diet (especially rodents are commonly used in obesity research. The effect of dietary fat on body fat accumulation is not fully understood in zebrafish, an excellent model of vertebrate lipid metabolism. Here, we explored the effects of dietary fat and green tea extract, which has anti-obesity properties, on body fat accumulation in zebrafish. Adult zebrafish were allocated to four diet groups and over 6 weeks were fed a high-fat diet containing basal diet plus two types of fat or a low-fat diet containing basal diet plus carbohydrate or protein. Another group of adult zebrafish was fed a high-fat diet with or without 5% green tea extract supplementation. Zebrafish fed the high-fat diets had nearly twice the body fat (visceral, subcutaneous, and total fat volume and body fat volume ratio (body fat volume/body weight of those fed low-fat diets. There were no differences in body fat accumulation between the two high-fat groups, nor were there any differences between the two low-fat groups. Adding green tea extract to the high-fat diet significantly suppressed body weight, body fat volume, and body fat volume ratio compared with the same diet lacking green tea extract. 3-Hydroxyacyl-coenzyme A dehydrogenase and citrate synthase activity in the liver and skeletal muscle were significantly higher in fish fed the diet supplemented with green tea extract than in those fed the unsupplemented diet. Our results suggest that a diet rich in fat, instead of protein or carbohydrate, induced body fat accumulation in zebrafish with mechanisms that might be similar to those in mammals. Consequently, zebrafish might serve as a good animal model for research into obesity induced by high-fat diets.

Activation of hindbrain neurons in response to gastrointestinal lipid is attenuated by high fat, high energy diets in mice prone to diet-induced obesity.

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Donovan, Michael J; Paulino, Gabriel; Raybould, Helen E

2009-01-12

Food intake is controlled by peripheral signals from the gastrointestinal tract and adipocytes, which are integrated within the central nervous system. There is evidence that signals from the GI tract are modulated by long term changes in diet, possibly leading to hyperphagia and increased body weight. We tested the hypothesis that diet-induced obese-prone (DIO-P) and obese-resistant (DIO-R) mice strains differ in the long term adaptive response of the gut-brain pathway to a high fat diet. Immunochemical detection of Fos protein was used as a measure of neuronal activation in the nucleus of the solitary tract (NTS) in response to intragastric administration of lipid in DIO-P (C57Bl6) and DIO-R (129sv) mouse strains maintained on chow or high fat, high energy diets (45% or 60% kcal from fat). Intragastric lipid administration activated neurons in the NTS in both DIO-P and DIO-R mice; the number of activated neurons was significantly greater in DIO-P than in DIO-R mice (Pdiet, for 4 or 8 weeks, compared to chow fed controls (Pdiet (45% or 60%) had no effect on lipid-induced activation of NTS neurons. These results demonstrate that DIO-P and DIO-R mice strains differ in the adaptation of the pathway to long term ingestion of high fat diets, which may contribute to decrease satiation and increased food intake.

Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.

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Young, Lindsay R; Kurzer, Mindy S; Thomas, William; Redmon, J Bruce; Raatz, Susan K

2013-07-01

The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in healthy individuals are not well defined. Three test diets-high-fat diet (40% energy as fat), low-fat diet (LF; 20% energy as fat), and a diet with low fat and high omega-3 fatty acid (LFn3; 23% energy as fat)--were tested in a randomized crossover designed controlled feeding trial in healthy postmenopausal women. Plasma IGF-I, IGF binding protein-3 (IGFBP-3), insulin, glucose, and ratio of IGF-I/IGFBP-3 concentrations were measured in response to diets. Insulin sensitivity was calculated using the homeostatic model assessment of insulin resistance We hypothesized that IGF-I, insulin, and glucose concentrations would decrease and IGFBP-3 concentration would increase in response to the low-fat diets. Eight weeks of the LFn3 diet increased circulating IGF-I (P diet increased IGFBP-3 (P = .04), resulting in trends toward an increased IGF-I/IGFBP-3 ratio with the LFn3 diet and a decreased IGF-I/IGFBP-3 ratio with the LF diet (P = .13 for both comparisons). No statistically significant differences were detected between treatments at baseline or 8 weeks for IGF-1, IGFBP-3, or the ratio of IGF-1/IGFBP-3. Insulin, glucose, and the homeostatic model assessment of insulin resistance were not altered by the interventions. Low-fat diet with high n-3 fatty acids may increase circulating IGF-I concentrations without adversely affecting insulin sensitivity in healthy individuals. Published by Elsevier Inc.

Brain transcriptional responses to high-fat diet in Acads-deficient mice reveal energy sensing pathways.

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Claudia Kruger

Full Text Available How signals from fatty acid metabolism are translated into changes in food intake remains unclear. Previously we reported that mice with a genetic inactivation of Acads (acyl-coenzyme A dehydrogenase, short-chain, the enzyme responsible for mitochondrial beta-oxidation of C4-C6 short-chain fatty acids (SCFAs, shift consumption away from fat and toward carbohydrate when offered a choice between diets. In the current study, we sought to indentify candidate genes and pathways underlying the effects of SCFA oxidation deficiency on food intake in Acads-/- mice.We performed a transcriptional analysis of gene expression in brain tissue of Acads-/- and Acads+/+ mice fed either a high-fat (HF or low-fat (LF diet for 2 d. Ingenuity Pathway Analysis revealed three top-scoring pathways significantly modified by genotype or diet: oxidative phosphorylation, mitochondrial dysfunction, and CREB signaling in neurons. A comparison of statistically significant responses in HF Acads-/- vs. HF Acads+/+ (3917 and Acads+/+ HF vs. LF Acads+/+ (3879 revealed 2551 genes or approximately 65% in common between the two experimental comparisons. All but one of these genes were expressed in opposite direction with similar magnitude, demonstrating that HF-fed Acads-deficient mice display transcriptional responses that strongly resemble those of Acads+/+ mice fed LF diet. Intriguingly, genes involved in both AMP-kinase regulation and the neural control of food intake followed this pattern. Quantitative RT-PCR in hypothalamus confirmed the dysregulation of genes in these pathways. Western blotting showed an increase in hypothalamic AMP-kinase in Acads-/- mice and HF diet increased, a key protein in an energy-sensing cascade that responds to depletion of ATP.Our results suggest that the decreased beta-oxidation of short-chain fatty acids in Acads-deficient mice fed HF diet produces a state of energy deficiency in the brain and that AMP-kinase may be the cellular energy

Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

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Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even

2016-01-01

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein....../sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our...... findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue...

High fat diet drives obesity regardless the composition of gut microbiota in mice.

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Rabot, Sylvie; Membrez, Mathieu; Blancher, Florence; Berger, Bernard; Moine, Déborah; Krause, Lutz; Bibiloni, Rodrigo; Bruneau, Aurélia; Gérard, Philippe; Siddharth, Jay; Lauber, Christian L; Chou, Chieh Jason

2016-08-31

The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1(st) week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice.

A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats.

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Sandoval-Salazar, Cuauhtemoc; Ramírez-Emiliano, Joel; Trejo-Bahena, Aurora; Oviedo-Solís, Cecilia I; Solís-Ortiz, Martha Silvia

2016-02-29

It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats. The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats. HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

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

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Jurgoński, Adam; Juśkiewicz, Jerzy; Zduńczyk, Zenon

2014-02-03

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

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

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Adam Jurgoński

2014-02-01

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

The role of dietary fat in obesity-induced insulin resistance.

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Lackey, Denise E; Lazaro, Raul G; Li, Pingping; Johnson, Andrew; Hernandez-Carretero, Angelina; Weber, Natalie; Vorobyova, Ivetta; Tsukomoto, Hidekazu; Osborn, Olivia

2016-12-01

Consumption of excess calories results in obesity and insulin resistance and has been intensively studied in mice and humans. The objective of this study was to determine the specific contribution of dietary fat rather than total caloric intake to the development of obesity-associated insulin resistance. We used an intragastric feeding method to overfeed excess calories from a low-fat diet (and an isocalorically matched high-fat diet) through a surgically implanted gastric feeding tube to generate obesity in wild-type mice followed by hyperinsulinemic-euglycemic clamp studies to assess the development of insulin resistance. We show that overfeeding a low-fat diet results in levels of obesity similar to high-fat diet feeding in mice. However, despite a similar body weight, obese high-fat diet-fed mice are more insulin resistant than mice fed an isocaloric low-fat diet. Therefore, increased proportion of calories from dietary fat further potentiates insulin resistance in the obese state. Furthermore, crossover diet studies revealed that reduction in dietary fat composition improves glucose tolerance in obesity. In the context of the current obesity and diabetes epidemic, it is particularly important to fully understand the role of dietary macronutrients in the potentiation and amelioration of disease. Copyright © 2016 the American Physiological Society.

Phytosterol-deficient and high-phytosterol diets developed for controlled feeding studies.

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Racette, Susan B; Spearie, Catherine Anderson; Phillips, Katherine M; Lin, Xiaobo; Ma, Lina; Ostlund, Richard E

2009-12-01

Phytosterols reduce cholesterol absorption and low-density lipoprotein cholesterol concentrations, but the quantity and physiological significance of phytosterols in common diets are generally unknown because nutrient databases do not contain comprehensive phytosterol data. The primary aim of this study was to design prototype phytosterol-deficient and high-phytosterol diets for use in controlled feeding studies of the influence of phytosterols on health. A second aim was to quantify the phytosterol content of these prototype diets and three other diets consumed in the United States. This study was conducted from June 2001 to September 2008 and involved designing, preparing, and then analyzing five different diets: an experimental phytosterol-deficient control diet, a relatively high-phytosterol diet based on the Dietary Approaches to Stop Hypertension diet, American Heart Association diet, Atkins lifetime maintenance plan, and a vegan diet. A single day of meals for each diet was homogenized and the resulting composites were analyzed for free, esterified, and glycosylated phytosterols by gas chromatography. Independent samples t tests were used to compare the diets' total phytosterol content. The total phytosterol content of the experimental phytosterol-deficient diet was 64 mg/2,000 kcal, with progressively larger quantities in Atkins, American Heart Association, vegan, and the high-phytosterol Dietary Approaches to Stop Hypertension diet (163, 340, 445, and 500 mg/2,000 kcal, respectively). Glycosylated phytosterols, which are often excluded from phytosterol analyses, comprised 15.9%+/-5.9% of total phytosterols. In summary, phytosterol-deficient and high-phytosterol diets that conform to recommended macronutrient guidelines and are palatable can now be used in controlled feeding studies.

Evaluation of corn germ from ethanol production as an alternative fat source in dairy cow diets.

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Abdelqader, M M; Hippen, A R; Kalscheur, K F; Schingoethe, D J; Karges, K; Gibson, M L

2009-03-01

Sixteen multiparous cows (12 Holstein and 4 Brown Swiss, 132 +/- 20 d in milk) were used in a replicated 4 x 4 Latin square design with 4-wk periods to determine the effects of feeding corn germ on dairy cow performance. Diets were formulated with increasing concentrations of corn germ (Dakota Germ, Poet Nutrition, Sioux Falls, SD) at 0, 7, 14, and 21% of the diet dry matter (DM). All diets had a 55:45 forage to concentrate ratio, where forage was 55% corn silage and 45% alfalfa hay. Dietary fat increased from 4.8% in the control diet to 8.2% at the greatest inclusion level of corn germ. The addition of corn germ resulted in a quadratic response in DM intake with numerically greater intake at 14% of diet DM. Feeding corn germ at 7 and 14% of diet DM increased milk yield and energy-corrected milk as well as fat percentage and yield. Milk protein yield tended to decrease as the concentration of corn germ increased in the diet. Dietary treatments had no effect on feed efficiency, which averaged 1.40 kg of energy-corrected milk/kg of DMI. Increasing the dietary concentration of corn germ resulted in a linear increase in milk fat concentrations of monounsaturated and polyunsaturated fatty acids at the expense of saturated fatty acids. Milk fat concentration and yield of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid were increased with increased dietary concentrations of corn germ. Although milk fat concentrations of both total trans-18:1 and cis-18:1 fatty acids increased linearly, a marked numeric increase in the concentration of trans-10 C18:1 was observed in milk from cows fed the 21% corn germ diet. A similar response was observed in plasma concentration of trans-10 C18:1. Feeding increasing concentrations of corn germ had no effect on plasma concentrations of glucose, triglyceride, or beta-hydroxybutyrate; however, the concentration of nonesterified fatty acids increased linearly, with plasma cholesterol concentration demonstrating a similar trend

Finger millet bran supplementation alleviates obesity-induced oxidative stress, inflammation and gut microbial derangements in high-fat diet-fed mice.

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Murtaza, Nida; Baboota, Ritesh K; Jagtap, Sneha; Singh, Dhirendra P; Khare, Pragyanshu; Sarma, Siddhartha M; Podili, Koteswaraiah; Alagesan, Subramanian; Chandra, T S; Bhutani, K K; Boparai, Ravneet K; Bishnoi, Mahendra; Kondepudi, Kanthi Kiran

2014-11-14

Several epidemiological studies have shown that the consumption of finger millet (FM) alleviates diabetes-related complications. In the present study, the effect of finger millet whole grain (FM-WG) and bran (FM-BR) supplementation was evaluated in high-fat diet-fed LACA mice for 12 weeks. Mice were divided into four groups: control group fed a normal diet (10 % fat as energy); a group fed a high-fat diet; a group fed the same high-fat diet supplemented with FM-BR; a group fed the same high-fat diet supplemented with FM-WG. The inclusion of FM-BR at 10 % (w/w) in a high-fat diet had more beneficial effects than that of FM-WG. FM-BR supplementation prevented body weight gain, improved lipid profile and anti-inflammatory status, alleviated oxidative stress, regulated the expression levels of several obesity-related genes, increased the abundance of beneficial gut bacteria (Lactobacillus, Bifidobacteria and Roseburia) and suppressed the abundance of Enterobacter in caecal contents (P≤ 0·05). In conclusion, FM-BR supplementation could be an effective strategy for preventing high-fat diet-induced changes and developing FM-BR-enriched functional foods.

Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention

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Lu, Yunxia, E-mail: wwwdluyx@sina.com [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032 (China); Cheng, Jingjing [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Chen, Li [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Department of Medical Laboratory, Anhui Provincial Hospital, Hefei, Anhui 230001 (China); Li, Chaofei; Chen, Guanjun [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Gui, Li [The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032 (China); Shen, Bing [Department of Physiology, Anhui Medical University, Hefei, Anhui 230032 (China); Zhang, Qiu [Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022 (China)

2015-02-27

Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown. In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in primary mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We found that FF treatment improved serum lipid levels and pathological changes in thoracic aorta, accompanied with decreased ER stress and increased phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different concentrations of PA treatment. The dose- and time-dependent inhibition of cell proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and expression of ER stress related genes were all inverted by FA pretreatment in PA-treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic HFD feeding and acute stimulation of PA, this effect is related with decreased ER stress and increased phosphorylation of eNOS. - Highlights: • Fenofibrate treatment improved pathological changes in thoracic aorta by chronic high-fat-diet feeding. • Fenofibrate pretreatment improved endothelium-dependent vasodilation impaired by different concentrations of palmitic acid. • The inhibition of proliferation in endothelial cells by palmitic acid were inverted by fenofibric

Exercise training performed simultaneously to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in mice

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Farias JM

2012-10-01

Full Text Available Abstract Background The aim of the present study was to evaluate the protective effect of concurrent exercise in the degree of the insulin resistance in mice fed with a high-fat diet, and assess adiponectin receptors (ADIPOR1 and ADIPOR2 and endosomal adaptor protein APPL1 in different tissues. Methods Twenty-four mice were randomized into four groups (n = 6: chow standard diet and sedentary (C; chow standard diet and simultaneous exercise training (C-T; fed on a high-fat diet and sedentary (DIO; and fed on a high-fat diet and simultaneous exercise training (DIO-T. Simultaneously to starting high-fat diet feeding, the mice were submitted to a swimming exercise training protocol (2 x 30 minutes, with 5 minutes of interval/day, five days per week, for twelve weeks (90 days. Animals were then euthanized 48 hours after the last exercise training session, and adipose, liver, and skeletal muscle tissue were extracted for an immunoblotting analysis. Results IR, IRs, and Akt phosphorylation decreased in the DIO group in the three analyzed tissues. In addition, the DIO group exhibited ADIPOR1 (skeletal muscle and adipose tissue, ADIPOR2 (liver, and APPL1 reduced when compared with the C group. However, it was reverted when exercise training was simultaneously performed. In parallel, ADIPOR1 and 2 and APPL1 protein levels significantly increase in exercised mice. Conclusions Our findings demonstrate that exercise training performed concomitantly to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in the hepatic, adipose, and skeletal muscle tissue.

Serotonin Improves High Fat Diet Induced Obesity in Mice.

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Hitoshi Watanabe

Full Text Available There are two independent serotonin (5-HT systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

Serotonin Improves High Fat Diet Induced Obesity in Mice.

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Watanabe, Hitoshi; Nakano, Tatsuya; Saito, Ryo; Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

2016-01-01

There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

Effects of overfeeding and high-fat diet on cardiosomatic parameters and cardiac structures in young and adult zebrafish.

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Vargas, Rafael; Vásquez, Isabel Cristina

2017-12-01

Obesity is a complex global health problem because it is a risk factor for multiple chronic pathologies such as cardiovascular, endocrine, metabolic, and neoplastic diseases. It is considered a multicausal disease, and one of the determining factors is nutritional imbalances, which include high-fat diets. In this paper, we use the zebrafish model to assess the impact of overfeeding and a high-fat diet in somatic and cardiac parameters in young and adult zebrafish. The results show that fish receiving a high-fat diet showed greater weight gain compared to fish receiving a standard fat diet. Additionally, changes in the heart, including increases in size, a change in the triangular shape of the ventricle to a globular shape, and an increase in the thickness of the trabeculae of the spongy myocardium were observed. These changes could be indicators of cardiovascular overload. The results show that there is a direct relationship between the intake of a high-fat diet and obesity, which in turn can induce cardiac changes, supporting the hypothesis of the relationship between high-fat diets and cardiovascular risk factors. Given the genetic similarity between zebrafish and humans, these results could be extrapolated to human beings, and the findings similarly highlight the importance of incorporating a balanced diet from the early life stages to reduce the risk of cardiovascular disease.

Switching adolescent high-fat diet to adult control diet restores neurocognitive alterations

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Chloe Boitard

2016-11-01

Full Text Available In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence in adolescents is particularly alarming since this is a period of ongoing maturation for brain structures (including the hippocampus and amygdala and for the hypothalamic-pituitary-adrenal (HPA stress axis, which is required for cognitive and emotional processing. We recently demonstrated that adolescent, but not adult, high-fat diet (HF exposure leads to impaired hippocampal function and enhanced amygdala function through HPA axis alteration (Boitard et al., 2014; Boitard et al., 2012; Boitard et al., 2015. Here, we assessed whether the effects of adolescent HF consumption on brain function are permanent or reversible. After adolescent exposure to HF, switching to a standard chow diet restored levels of hippocampal neurogenesis and normalized enhanced HPA axis reactivity, amygdala activity and avoidance memory. Therefore, while the adolescent period is highly vulnerable to the deleterious effects of diet-induced obesity, adult exposure to a standard diet appears sufficient to reverse alterations of brain function.

Myristoylation of Src kinase mediates Src-induced and high-fat diet-accelerated prostate tumor progression in mice.

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Kim, Sungjin; Yang, Xiangkun; Li, Qianjin; Wu, Meng; Costyn, Leah; Beharry, Zanna; Bartlett, Michael G; Cai, Houjian

2017-11-10

Exogenous fatty acids provide substrates for energy production and biogenesis of the cytoplasmic membrane, but they also enhance cellular signaling during cancer cell proliferation. However, it remains controversial whether dietary fatty acids are correlated with tumor progression. In this study, we demonstrate that increased Src kinase activity is associated with high-fat diet-accelerated progression of prostate tumors and that Src kinases mediate this pathological process. Moreover, in the in vivo prostate regeneration assay, host SCID mice carrying Src(Y529F)-transduced regeneration tissues were fed a low-fat diet or a high-fat diet and treated with vehicle or dasatinib. The high-fat diet not only accelerated Src-induced prostate tumorigenesis in mice but also compromised the inhibitory effect of the anticancer drug dasatinib on Src kinase oncogenic potential in vivo We further show that myristoylation of Src kinase is essential to facilitate Src-induced and high-fat diet-accelerated tumor progression. Mechanistically, metabolism of exogenous myristic acid increased the biosynthesis of myristoyl CoA and myristoylated Src and promoted Src kinase-mediated oncogenic signaling in human cells. Of the fatty acids tested, only exogenous myristic acid contributed to increased intracellular myristoyl CoA levels. Our results suggest that targeting Src kinase myristoylation, which is required for Src kinase association at the cellular membrane, blocks dietary fat-accelerated tumorigenesis in vivo Our findings uncover the molecular basis of how the metabolism of myristic acid stimulates high-fat diet-mediated prostate tumor progression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.

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Martin, Gregory G; Landrock, Danilo; Chung, Sarah; Dangott, Lawrence J; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

2017-01-01

The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice. © 2016 International Society for Neurochemistry.

Maternal High Folic Acid Supplement Promotes Glucose Intolerance and Insulin Resistance in Male Mouse Offspring Fed a High-Fat Diet

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Yifan Huang

2014-04-01

Full Text Available Maternal nutrition may influence metabolic profiles in offspring. We aimed to investigate the effect of maternal folic acid supplement on glucose metabolism in mouse offspring fed a high-fat diet (HFD. Sixty C57BL/6 female mice were randomly assigned into three dietary groups and fed the AIN-93G diet containing 2 (control, 5 (recommended folic acid supplement, RFolS or 40 (high folic acid supplement, HFolS mg folic acid/kg of diet. All male offspring were fed HFD for eight weeks. Physiological, biochemical and genetic variables were measured. Before HFD feeding, developmental variables and metabolic profiles were comparable among each offspring group. However, after eight weeks of HFD feeding, the offspring of HFolS dams (Off-HFolS were more vulnerable to suffer from obesity (p = 0.009, glucose intolerance (p < 0.001 and insulin resistance (p < 0.001, compared with the controls. Off-HFolS had reduced serum adiponectin concentration, accompanied with decreased adiponectin mRNA level but increased global DNA methylation level in white adipose tissue. In conclusion, our results suggest maternal HFolS exacerbates the detrimental effect of HFD on glucose intolerance and insulin resistance in male offspring, implying that HFolS during pregnancy should be adopted cautiously in the general population of pregnant women to avoid potential deleterious effect on the metabolic diseases in their offspring.

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

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Seong-Jong Lee

2015-01-01

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

Whey protein reduces early life weight gain in mice fed a high-fat diet

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Tranberg, Britt; Hellgren, Lars; Lykkesfeldt, Jens

2013-01-01

An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would...... be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel...... reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota...

Comparison of effects of long-term low-fat vs high-fat diets on blood lipid levels in overweight or obese patients: a systematic review and meta-analysis.

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Schwingshackl, Lukas; Hoffmann, Georg

2013-12-01

Dietary fat plays an important role in the primary prevention of cardiovascular disease, but long-term (≥12 months) effects of different percentages of fat in the diet on blood lipid levels remain to be established. Our systematic review and meta-analysis focused on randomized controlled trials assessing the long-term effects of low-fat diets compared with diets with high amounts of fat on blood lipid levels. Relevant randomized controlled trials were identified searching MEDLINE, EMBASE, and the Cochrane Trial Register until March 2013. Thirty-two studies were included in the meta-analysis. Decreases in total cholesterol (weighted mean difference -4.55 mg/dL [-0.12 mmol/L], 95% CI -8.03 to -1.07; P=0.01) and low-density lipoprotein (LDL) cholesterol (weighted mean difference -3.11 mg/dL [-0.08 mmol/L], 95% CI -4.51 to -1.71; Plow-fat diets, whereas rise in high-density lipoprotein (HDL) cholesterol (weighted mean difference 2.35 mg/dL [0.06 mmol/L], 95% CI 1.29 to 3.42; Pfat diet groups. Including only hypocaloric diets, the effects of low-fat vs high-fat diets on total cholesterol and LDL cholesterol levels were abolished. Meta-regression revealed that lower total cholesterol level was associated with lower intakes of saturated fat and higher intakes of polyunsaturated fat, and increases in HDL cholesterol levels were related to higher amounts of total fat largely derived from monounsaturated fat (of either plant or animal origin) in high-fat diets (composition of which was ~17% of total energy content in the form of monounsaturated fatty acids, ~8% of total energy content in the form of polyunsaturated fatty acids), whereas increases in triglyceride levels were associated with higher intakes of carbohydrates. In addition, lower LDL cholesterol level was marginally associated with lower saturated fat intake. The results of our meta-analysis do not allow for an unequivocal recommendation of either low-fat or high-fat diets in the primary prevention of

High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects.

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Greta Jakobsdottir

Full Text Available Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs, particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation.To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks.Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin - acetic acid; guar gum - propionic acid; or a mixture - butyric acid. At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks.Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet.

Effect of One Month Duration Ketogenic and non-Ketogenic High Fat Diets on Mouse Brain Bioenergetic Infrastructure