Running Exercise Improves Metabolic Abnormalities and Fat Accumulation in Sucrose-Induced Insulin-Resistant Rats

NARA, MAKOTO, MASAKI TAKAHASHI, TSUGIYASU KANDA, YOUNOSUKE SHIMOMURA, ISAO KOBAYASHI. Running exercise improves metabolic abnormalities and fat accumulation in sucrose-induced insulin-resistant rats. Insulin resistance and hyperinsulinemia are observed in rats fed a high sucrose diet. Insulin resistance is thought to be related to abnormal fat distribution. We previously reported the metabolic characteristics and the fat distribution in rats with sucrose-induced insulin resistance. This study was designed to examine the effects of exercise in these rats. The rats were divided into three groups: those receiving a starch-based diet (control), those receiving a high-sucrose diet (sucrose fed), and those receiving a high-sucrose diet and wheel-running exercise (exercised). Animals were killed after 4 weeks or 12 weeks. After 4 weeks, the three groups did not differ with respect to gain in adipose tissues. The portal vein (PV) insulin concentration was significantly increased in the sucrose-fed and the exercised rats compared with the control rats. The inferior vena cava (IVC) glucose concentration and the PV free fatty acid (FFA) were significantly lower in the exercised rats than in the sucrose-fed rats. After 12 weeks, the exercised rats had significantly lower mesenteric fat (MS) and subcutaneous fat (SC) and a lower MS:SC ratio than the sucrose-fed rats. The glucose levels in IVC, PV, and FFA in PV were significantly reduced in the exercised rats as compared with the sucrose-fed rats. These findings suggest that long-term exercise improves insulin resistance by reducing the accumulation of MS as well as SC. It is also suggested that short-term exercise improves glucose metabolism without change of fat accumulation.     

Regulation of glucose transport and transporter 4 (GLUT-4) in muscle and adipocytes of sucrose-fed rats: effects of N-3 poly- and monounsaturated fatty acids.

The goal of this study was to compare the short-term effects of dietary n-3 polyunsaturated (fish oil) and monounsaturated (olive oil) fatty acids on glucose transport, plasma glucose and lipid controls in a dietary insulin resistance model using sucrose-fed rats. The underlying cellular and molecular mechanisms were also determined in the muscle and adipose tissue. Male Sprague-Dawley rats (5 weeks old) were randomized for diets containing 57.5 % (w/w) sucrose and 14 % lipids as either fish oil (SF), olive oil (SO) or a mixture of standard oils (SC) for 3 weeks. A fourth control group (C) was fed a diet containing 57.5 % starch and 14 % standard oils. After three weeks on the diet, body weight was comparable in the four groups. The sucrose-fed rats were hyperglycemic and hyperinsulinemic in response to glucose load. The presence of fish oil in the sucrose diet prevented sucrose-induced hyperinsulinemia and hypertriglyceridemia, but had no effect on plasma glucose levels. Insulin-stimulated glucose transport in adipocytes increased after feeding with fish oil (p < 0.005). These modifications were associated with increased Glut-4 protein (p < 0.05) and mRNA levels in adipocytes. In the muscle, no effect was found on Glut-4 protein levels. Olive oil, however, could not bring about any improvement in plasma insulin, plasma lipids or Glut-4 protein levels. We therefore conclude that the presence of fish oil, in contrast to olive oil, prevents insulin resistance and hypertriglyceridemia in rats on a sucrose diet, and restores Glut-4 protein quantity in adipocytes but not in muscle at basal levels. Dietary regulation of Glut-4 proteins appears to be tissue specific and might depend on insulin stimulation and/or duration of dietary interventions.     

β‐Adrenergic‐AMPK Pathway Phosphorylates Acetyl‐CoA Carboxylase in a High‐epinephrine Rat Model,SPORTS

We established a new animal model called SPORTS (Spontaneously‐Running Tokushima‐Shikoku) rats, which show high‐epinephrine (Epi) levels. Recent reports show that Epi activates adenosine monophosphate (AMP)–activated protein kinase (AMPK) in adipocytes. Acetyl‐CoA carboxylase (ACC) is the rate‐limiting enzyme in fatty acid synthesis, and the enzymatic activity is suppressed when its Ser‐79 is phosphorylated by AMPK. The aim of this study was to investigate the in vivo effect of Epi on ACC and abdominal visceral fat accumulation. We divided both 6‐week male control and SPORTS rats into two groups, which were fed either normal diet or high fat and sucrose (HFS) diet for 16 weeks. At the end of diet treatment, retroperitoneal fat was collected for western blotting and histological analysis. Food intake was not different among the groups, but SPORTS rats showed significantly lower weight gain than control rats in both diet groups. After 10 weeks of diet treatment, glucose tolerance tests (GTTs) revealed that SPORTS rats had increased insulin sensitivity. Furthermore, SPORTS rats had lower quantities of both abdominal fat and plasma triglyceride (TG). In abdominal fat, elevated ACC Ser‐79 phosphorylation was observed in SPORTS rats and suppressed by an antagonist of β‐adrenergic receptor (AR), propranolol, or an inhibitor of AMPK, Compound C. From these results, high level of Epi induced ACC phosphorylation mediated through β‐AR and AMPK signaling pathways in abdominal visceral fat of SPORTS rats, which may contribute to reduce abdominal visceral fat accumulation and increase insulin sensitivity. Our results suggest that β‐AR‐regulated ACC activity would be a target for treating lifestyle‐related diseases, such as obesity.     

Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-lesioned obese rats

To determine the influence of dietary fructose and glucose on circulating leptin levels in lean and obese rats, plasma leptin concentrations were measured in ventromedial hypothalamic (VMH)-lesioned obese and sham-operated lean rats fed either normal chow or fructose- or glucose-enriched diets (60% by calories) for 2 wk. Insulin resistance was evaluated by the steady-state plasma glucose method and intravenous glucose tolerance test. In lean rats, glucose-enriched diet significantly increased plasma leptin with enlarged parametrial fat pad, whereas neither leptin nor fat-pad weight was altered by fructose. Two weeks after the lesions, the rats fed normal chow had marked greater body weight gain, enlarged fat pads, and higher insulin and leptin compared with sham-operated rats. Despite a marked adiposity and hyperinsulinemia, insulin resistance was not increased in VMH-lesioned rats. Fructose brought about substantial insulin resistance and hyperinsulinemia in both lean and obese rats, whereas glucose led to rather enhanced insulin sensitivity. Leptin, body weight, and fat pad were not significantly altered by either fructose or glucose in the obese rats. These results suggest that dietary glucose stimulates leptin production by increasing adipose tissue or stimulating glucose metabolism in lean rats. Hyperleptinemia in VMH-lesioned rats is associated with both increased adiposity and hyperinsulinemia but not with insulin resistance. Dietary fructose does not alter leptin levels, although this sugar brings about hyperinsulinemia and insulin resistance, suggesting that hyperinsulinemia compensated for insulin resistance does not stimulate leptin production.     

Hepatic and adipose tissue lipogenic enzyme mRNA levels are suppressed by high fat diets in the rat

Small changes in lipogenic enzyme activity induced by dietary fats of different composition may, over the long term, have significant impact on the development of obesity. We have investigated the effect of high fat diets (45% of calories as fat) on abundance of mRNA encoding fatty acid synthetase (FAS) and glycerophosphate dehydrogenase (GPDH) in male Sprague-Dawley rats. When caloric intake was equal, the relative amount of hepatic FAS mRNA was greater in rats fed a saturated compared to a polyunsaturated fat diet. This difference could not be attributed to diet-induced changes in plasma insulin concentration. However, both fat diets suppressed hepatic FAS mRNA compared to a sucrose diet. Close correlation between FAS specific activity and the relative amount of mRNA suggested that regulation was mainly at a pre-translational level. Adipose tissue FAS mRNA was suppressed by the two fat diets equally while GPDH mRNA was unaffected by dietary composition. Retroperitoneal fat pads were significantly larger in rats fed saturated compared to those fed polyunsaturated fat for 26 weeks. We concluded that dietary saturated fats fail to suppress hepatic de novo lipogenesis as effectively as polyunsaturated fats, which may have implications for the prevention of obesity in humans.     

Changes of skeletal muscle adiponectin content in diet-induced insulin resistant rats

The current study examined the relationship between skeletal muscle levels of adiponectin and parameters of insulin sensitivity. A high fat/sucrose diet (HFD) for 20 weeks resulted in significant increases in body weight, serum insulin, triglycerides (TG), and free fatty acids (FFA) (all p < 0.01). Interestingly, this diet leads to a slight increase in serum adiponectin, but significant decreases in gastrocnemius muscle and white adipose adiponectin (all p < 0.05). HFD for 4 weeks also resulted in a significant decrease in muscle adiponectin, which correlated with serum insulin, TG, and FFA (all p < 0.05). Treatment of the 4-week HFD rats with a PPARgamma agonist GI262570 ameliorated the diet-induced hyperinsulinemia and dyslipidemia, and effectively restored muscle adiponectin (all p < 0.05). This study demonstrated that HFD-induced hyperinsulinemia and dyslipidemia appeared without changes in serum adiponectin, but were associated with decreased tissue adiponectin. This provides the first evidence for a connection between tissue adiponectin and diet-induced hyperinsulinemia and dyslipidemia.     

Excessive Energy Intake Does Not Modify Fed‐state Tissue Protein Synthesis Rates in Adult Rats

The impact of chronic excessive energy intake on protein metabolism is still controversial. Male Wistar rats were fed ad libitum during 5 weeks with either a high‐fat high‐sucrose diet (HF: n = 9) containing 45% of total energy as lipids (protein 14%; carbohydrate 40% with 83.5% sucrose) or a standard diet (controls: n = 10). Energy intake and body weight were recorded. At the end of the experiment, we measured body composition, metabolic parameters (plasma amino acid, lipid, insulin, and glucose levels), inflammatory parameter (plasma α2‐macroglobulin), oxidative stress parameters (antioxidant enzyme activities, lipoperoxidation (LPO), protein carbonyl content in liver and muscle), and in vivo fed–state fractional protein synthesis rates (FSRs) in muscle and liver. Energy intake was significantly higher in HF compared with control rats (+28%). There were significant increases in body weight (+8%), body fat (+21%), renal (+41%), and epidydimal (+28%) fat pads in HF compared with control rats. No effect was observed in other tissue weights (liver, muscle, spleen, kidneys, intestine). Liver and muscle FSRs, plasma levels of lipids, glucose, insulin and α2‐macroglobulin, soleus and liver glutathione reductase and peroxidase acitivities, MnSOD activity, LPO, and protein carbonyl content were not altered by the HF diet. Only soleus muscle and liver Cu/ZnSOD activity and soleus muscle catalase activities were reduced in HF rats compared with control rats. Thus, chronic excessive energy intake and increased adiposity, in the absence of other metabolic alterations, do not stimulate fed‐state tissue protein synthesis rates.     

Isocaloric intake of a high‐fat diet promotes insulin resistance and inflammation in Wistar rats

The aim of this study was to investigate the effect of isocaloric intake from a high‐fat diet (HFD) on insulin resistance and inflammation in rats. Male Wistar rats were fed on an HFD (n = 12) or control diet (n = 12) for 12 weeks. Subsequently, all animals were euthanized, and blood glucose, insulin, free fatty acids, C‐reactive protein, lipid profile, cytokines and hepatic‐enzyme activity were determined. Carcass chemical composition was also analyzed. During the first and the twelfth weeks of the experimental protocol, the oral glucose tolerance test and insulin tolerance test were performed and demonstrated insulin resistance (P < 0.05) in the HFD group. Although food intake (g) was lower (P < 0.05) in the HFD group compared with the control group, the concentration of total cholesterol, low‐density lipoprotein, C‐reactive protein and liver weight were all significantly higher. The kinase inhibitor of κB, c‐Jun N‐terminal kinase and protein kinase B expressions were determined in the liver and skeletal muscle. After an insulin stimulus, the HFD group demonstrated decreased (P = 0.05) hepatic protein kinase B expression, whereas the kinase inhibitor of κB phospho/total ratio was elevated in the HFD muscle (P = 0.02). In conclusion, the isocaloric intake from the HFD induced insulin resistance, associated with impaired insulin signalling in the liver and an inflammatory response in the muscle. Copyright © 2012 John Wiley & Sons, Ltd.     

Diet and diabetic state modify glycogen synthase activity and expression in rat hepatocytes

Glycogen synthase (GS), a key regulatory enzyme in glycogen synthesis, is controlled by multisite phosphorylation and allosteric regulation and is activated by insulin. This study investigated changes in GS activity and expression in hepatocytes isolated from rats under altered nutritional and diabetic conditions. Experiments were carried out in healthy rats fed a chow diet, rats on high simple sugar (60% of energy from fructose and sucrose) or high fat (46% of energy from fat) diet, and in rats with streptozotocin induced diabetes. In the presence of insulin, activated GS activity (GS(I) form) was increased by 89% in hepatocytes isolated from healthy rats. The stimulatory effect of insulin on GS activity and expression was blunted by cycloheximide and actinomycin treatment. In rats fed a high simple sugar or high fat diet, insulin stimulation of GS(I) in isolated hepatocytes was impaired and GS expression was significantly lower in rats fed the high fat diet in comparison to controls. GLUT-2 protein expression was significantly lowered by both the high fat and high simple sugar diets. In hepatocytes isolated from diabetic rats, total GS activity (GS(T)) was lower than in hepatocytes from healthy animals. Insulin added to the incubation medium did not stimulate GS activity, demonstrating impaired sensitivity to insulin in diabetic rats. However, insulin administration significantly increased GS expression indicating that a defect in synthase phosphorylation may be responsible for impaired GS activity in the diabetic state. The results presented in this study further confirm that GS activity is affected by both dietary and hormonal factors which can be measured in a rat hepatocyte model.     

The inflammatory profile and liver damage of a sucrose-rich diet in mice

It is still unclear if an isoenergetic, sucrose-rich diet leads to health consequences.AimsTo investigate the effects of excessive sucrose within an isoenergetic diet on metabolic parameters in male C57BL/6 mice.MethodsAnimals were fed a control diet (10% fat, 8% sucrose — SC group), a high-sucrose diet (10% fat, 32% sucrose — HSu group), a high-fat diet (42% fat, 8% sucrose — HF group) or a high-fat/high-sucrose diet (42% fat, 32% sucrose — HF/HSu group) for 8 weeks.ResultsMice fed HF and HF/HSu diets gained more body mass (BM) and more body adiposity than SC- or Hsu-fed mice. Despite the unchanged BM and adiposity indices, HSu mice presented adipocyte hypertrophy, which was also observed in the HF and HF/HSu groups (P<.0001). The HF, HSu and HF/HSu mice were glucose intolerant and had elevated serum insulin levels (P<.05). The levels of leptin, resistin and monocyte chemotactic protein-1 increased, while the serum adiponectin decreased in the HF, HSu and HF/HSu groups (P<.05). In the adipose tissue, the HF, HSu and HF/HSu groups showed higher levels of leptin expression and lower levels of adiponectin expression in comparison with the SC group (P<.05). Liver steatosis was higher in the HF, HSu and HF/HSu groups than in the SC group (P<.0001). Hepatic cholesterol was higher in the HF and HF/HSu groups, while hepatic TG was higher in the HSu and HF/HSu groups (P<.05). In hepatic tissue, the sterol receptor element-binding protein-1c expression was increased in the HF, HSu and HF/HSu groups, unlike the peroxisome proliferator-activated receptor-alpha expression that decreased in the HF, HSu and HF/HSu groups in comparison with the SC group (P<.05).ConclusionA sucrose-rich diet does not lead to a state of obesity but has the potential to cause changes in the adipocytes (hypertrophy) as well as glucose intolerance, hyperinsulinemia, hyperlipidemia, hepatic steatosis and increases in the number of inflammatory cytokines. The deleterious effects of a sucrose-rich diet in an animal model, even when the sucrose replaces starch isocalorically in the feed, can have far-reaching consequences for health.     

Protective effect of ascorbic acid against lipid peroxidation and oxidative damage in cardiac microsomes

Effects of feeding sucrose rich diet supplemented with and without the insulinmimetic agent vanadate for a period of six weeks were studied in rats. Sucrose diet caused hypertriglyceridemia (140% increase), hyperinsulinemia (120% increase) and significant elevations in the levels of glucose (p<0.001) and cholesterol (p<0.05) in plasma as compared to control starch fed rats. Activities of hepatic lipogenic enzymes, ATP-citrate lyase, glucose 6-phosphate dehydrogenase and malic enzyme increased by 100–150% as a result of sucrose feeding. However, glycogen content and the activities of glycogen synthase and phosphorylase in liver remained unaltered in these animals. The plasma levels of triacylglycerols and insulin in the rats fed on vanadate supplemented sucrose diet were 65% and 85% less, respectively as compared to rats on sucrose diet without vanadate. The concentrations of glucose and cholesterol in plasma and the activities of lipogenic enzymes in liver did not show any elevation in sucrose fed rats when supplemented with vanadate. These data indicate that the sucrose diet-induced metabolic aberrations can be prevented by the insulin-mimetic agent, vanadate.     

Soy protein isolate in the presence of cornstarch reduces body fat gain in rats

The objective of the present study was to determine the combined effects of dietary protein and carbohydrate sources on total body energy and protein and fat gains as well as on plasma insulin and glucose and tissue lipoprotein lipase activity in male Sprague-Dawley rats fed semipurified diets for 28 days. The diets varied in both protein and carbohydrate sources, namely, casein-cornstarch, casein-sucrose, soy protein isolate (SPI)-cornstarch, SPI-sucrose, cod protein-cornstarch, and cod protein-sucrose. When SPI was combined with cornstarch, lower total body energy and fat gains were observed compared with the combination of either casein and sucrose, casein and cornstarch, or SPI and sucrose. Plasma glucose and insulin concentrations in addition to total and metabolizable energy intake and body weight gain were lower in rats fed the SPI-cornstarch diet than in those fed the casein-sucrose diet. Feeding the SPI-cornstarch diet compared with feeding either the casein-cornstarch or the SPI-sucrose diet also caused lower plasma glucose concentrations and a concomitant trend (p = 0.06) to reduced energy intake and body weight gain. Therefore, the reducing effects of the SPI-cornstarch diet compared with the casein-cornstarch, the casein-sucrose, and the SPI-sucrose diets on body energy and fat gains may result from reductions in energy intake and in plasma glucose concentrations.     

Insulin Action in Rats Is Influenced by Amount and Composition of Dietary Fat

The chronic influence of dietary fat composition on obesity and insulin action is not well understood. We examined the effect of amount (20% vs 60% of total calories) and type (saturated vs polyunsaturated) of fat on insulin action and body composition in mature male rats. Six months of feeding a high fat (HF) diet led to obesity and impaired insulin action (determined by a euglycemic-hyperinsulinemic clamp), neither of which were reversed by a subsequent 6 months of feeding a low fat (LF) diet. Within HF fed rats, type of fat did not affect body composition or insulin action. Six months of feeding a low fat diet led to only a slight decline in insulin action, with no difference due to type of dietary fat. From 6–9 months, insulin action became more impaired in LF rats fed the saturated diet than in LF rats fed the polyunsaturated diet. By 12 months, all groups were obese and had a similar impairment in insulin action. The amount and type of fat in the diet did not influence the overall degree of impairment in insulin action but did affect the time course. Both feeding a high fat diet and feeding a low fat saturated diet accelerated the impairment in insulin action relative to rats fed a low fat polyunsaturated fat diet.     

Altered Brown Adipose Tissue and Na,K Pump Activities During Diet-Induced Obesity and Weight Loss in Rats

Brown adipose tissue (BAT) thermogenesis is an uncoupled ATPase-independent thermogenic mechanism. Ion transport by the Na,K pump is an ATPase- dependent thermogenic mechanism. Both have been proposed as mechanisms of altered energy expenditure during states of dietary energy surfeit and deficit. Our aim was to study these mechanisms during diet-induced obesity and weight loss. Over 36 weeks rats were fed lard- or tallow-based diets (63% energy as fat), or a control diet (12% energy as fat). During periods of restriction rats were fed 50% of the energy intake of controls in the form of a control diet. Several components of thermogenic response increased in rats eating high fat diets and decreased following dietary restriction. BAT activation occurred, particularly with a lard-based diet, as indicated by increased GDP binding and uncoupling protein (UCP) content. Na,K pump activity in thymocytes increased with the feeding of both high fat diets at some time points. Plasma T₃ level increased in rats eating the lard-based diet and decreased with dietary restriction regardless of previous diet. Resting metabolic rate (RMR) of the animals was unchanged despite increases in these thermogenic components and was decreased in all groups following dietary restriction. Our results indicate a lack of any major role for activated BAT thermogenesis in mitigating the extent of the obesity induced by the high fat diets. The reasons for the differences in response to the two different sources of saturated fat, lard, and tallow, are not clear.     

Dietary fish oil reverse epididymal tissue adiposity, cell hypertrophy and insulin resistance in dyslipemic sucrose fed rat model small star, filled

The present work was designed to assess the possible benefits of (7% w/w) dietary fish oil in reversing the morphological and metabolic changes present in the adipose tissue of rats fed an SRD for a long time. With this purpose, in the epididymal fat tissue, we investigated the effect of dietary fish oil upon: i) the number, size and distribution of cells, ii) the basal and stimulated lipolysis, iii) the lipoprotein lipase (LPL) and the glucose 6-phosphate dehydrogenase activities, and iv) the antilipolytic action of insulin. The study was conducted on rats fed an SRD during 120 days with fish oil being isocaloric substituted for corn oil for 90-120 days in half the animals. Permanent hypertriglyceridemia, insulin resistance and abnormal glucose homeostasis were present in the rats before the source of fat in the diet was replaced. The major new findings of this study are the following: i) Dietary fish oil markedly reduced the fat pads mass, the hypertrophy of fat cells and improved the altered cell size distribution. ii) The presence of fish oil in the diet corrected the inhibitory effect of high sucrose diet upon the antilipolytic action of insulin, reduced the "in vitro" enhanced basal lipolysis and normalized isoproterenol-stimulated lipolysis. Fat pads lipoprotein lipase activity decreased reaching values similar to those observed in age-matched controls fed a control diet (CD). These effects were not accompanied by any change in rat body weight. All these data suggest that the dyslipemic rats fed a moderate amount of dietary fish oil constitute a useful animal model to study diet-regulated insulin action.     

Adult Female Rats Defend “Appropriate” Energy Intake after Adaptation to Dietary Energy

Objective: To determine if adult female rats adapt to lower and higher dietary energy density. Research Methods and Procedures: Study 1 compared high‐fat (56%), high‐energy density (HD) (21.6 kJ/g) and high‐fat (56%), low‐energy density (LD) (16.0 kJ/g) diets before surgery (two groups, 2 weeks, n = 16) and after surgery [ovariectomy (O) Sham (S); 2 × 2 factorial, n = 8; 6 weeks]. The second study (no surgery) compared high‐fat (60.0%), high‐energy (22.0 kJ/g) and low‐fat (10.0%), low‐energy (15.1 kJ/g) diets (n = 8). Results: In study 1, food intake was similar for the first 2 weeks, but rats on the LD diet consumed less energy, gained less weight, and had lower nonfasted serum leptin (all p < 0.0001) than rats on the HD diet. After surgery, rats on the LD and HD diets had similar weight gain, but rats on the LD diet consumed more food (p < 0.0001) and less energy (p < 0.009). O rats consumed more food and gained more weight (p < 0.0001) than S rats. Results from study 2 were similar to those from study 1. Discussion: The results demonstrated that O and S surgery rats and rats with no surgery adjust their food intake to defend a level of energy intake. This defense only occurred after a 2‐week adaptation period. The major differences in final body weights and abdominal fat resulted from the initial 2 weeks before adaptation to energy density. Rats fed higher‐energy diets seemed to “settle” at a higher level of adiposity, and rats fed lower‐energy diets consumed more food to increase energy consumption.     

Beneficial effects of hydro-alcoholic extract of Caralluma fimbriata against high-fat diet-induced insulin resistance and oxidative stress in Wistar male rats

The main aim of this study was to investigate the beneficial effects of hydro-alcoholic extract of Caralluma fimbriata (CFE) on the effects of high-fat diet feeding on insulin resistance and oxidative stress in Wistar rats. High-fat diet (60 % of fat) and CFE (200 mg/kg body weight/day) were given concurrently to the rats for a period of 90 days. Feeding with high-fat diet resulted in the development of hyperglycemia, hyperinsulinemia, hyperleptinemia, and hypertriglyceridemia and impaired insulin sensitivity (P?<?0.05). Administration of CFE to high-fat diet-fed rats for 90 days resulted in a significant improvement in plasma glucose, insulin, leptin, and triglycerides. Regarding liver antioxidant status, high-fat fed rats showed higher levels of lipid peroxidation, protein oxidation and lower GSH levels and lower activities of enzymatic antioxidants, while CFE treatment prevented all these observed abnormalities. In conclusion, intake of CFE may be beneficial for the suppression of high-fat diet-induced insulin resistance and oxidative stress.     

Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

Background

Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance.

Methodology/Principal Findings

We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein∶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state.

Conclusions/Significance

The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.     

Pigs fed saturated fat/cholesterol have a blunted hypothalamic-pituitary-adrenal function,are insulin resistant and have decreased expression of IRS-1, PGC1α and PPARα

The increasing incidence of insulin resistance has been linked to both increased intake of saturated fatty acids and disruption of the hypothalamic-pituitary-adrenal (HPA) axis. We tested the hypothesis that adding saturated fat/cholesterol to the diet of growing pigs would both disrupt HPA function and cause insulin resistance. Three-month-old pigs were fed either a control (13% energy from fat) or a high saturated fatty acid cholesterol (HSFC) diet (44% energy from fat; 2% cholesterol). After 10 weeks on the diets, intravenous ACTH, insulin and glucose challenges were performed, and after 12 weeks, tissue samples were taken for measurement of mRNA and for lipid-rich aortic lesions. Plasma total, HDL- and LDL-cholesterol were significantly increased in pigs fed the HSFC diet. Cortisol release during the ACTH challenge was suppressed in HSFC-fed pigs which were also more insulin resistant and glucose intolerant than controls. The HSFC diet decreased the expression of insulin receptor (IR) and insulin receptor substrate-1 in muscle and adipose tissue as well as adiponectin and adiponectin receptor 2 expression in fat. The HSFC diet decreased PGC-1α and PPARα expression in muscle but increased PPARα expression in liver. There was a trend for an increase in lipid-stained lesion frequency around the abdominal branches of the aorta in HSFC-fed pigs. We conclude that feeding increased saturated fat to pigs causes disruption in the HPA axis, insulin resistance and decreased muscle and adipose expression of genes controlling insulin signalling and mitochondrial oxidative capacity.     

Long-term effects of diet on leptin, energy intake, and activity in a model of diet-induced obesity.

This study investigated the effect of long-term high-fat sucrose (HFS) or low-fat complex-carbohydrate (LFCC) diet consumption on leptin, insulin, fat cell size, energy intake, and markers of activity to ascertain the role that leptin plays in long-term energy balance in a model of diet-induced obesity. Female Fischer 344 rats were fed either a HFS or LFCC diet ad libitum for a period of 20 mo. Measurements of leptin concentration, insulin concentration, and adipocyte size were performed at 2 wk, 2 mo, 6 mo, and 20 mo. Body weight and energy intake were measured weekly for calculation of feed efficiency. Body temperature and activity levels were assessed over a 5-day period after 12 mo of the dietary intervention. Plasma leptin and insulin concentrations were significantly elevated within 2 wk of HFS diet consumption and remained elevated throughout the course of the study. After 2 mo, the adipocytes of the HFS group were significantly larger and continued to increase in size throughout the course of the study. A significant correlation was noted between leptin and adipocyte cell size (r = 0.96, P < 0.01). However, despite elevated leptin, energy intake was similar, and the HFS group weighed significantly more than the LFCC group, as a result of a higher feed efficiency. There were no significant differences in body temperature or activity levels between the groups. These results demonstrate that a HFS diet causes hyperleptinemia and hyperinsulinemia before adipocyte size is increased and suggests that leptin resistance may be present or, alternatively, that leptin does not to play a major role in the long-term regulation of energy intake or activity levels in this model.