High fat diet

Our previous study, demonstrated the obesity-resistant phenomenon in the House musk shrew, Suncus murinus (S. murinus). In order to go further to explore the mechanism of the phenomenon of natural obesity resistance in S. murinus, we focused on the effects of diet on fat accumulation and metabolism. In this study, four-week-old male S. murinus were assigned to 1 of 2 experimental groups (n = 6 per group) and fed either a high-fat diet (HFD) or a normal trout diet (NTD) for 24 weeks. Body weight, food ingestion, visceral fat distribution, blood biochemistry and fecal lipids were monitored and analyzed in the HFD and NTD groups. It was found no differences in the average final body weight or body fat change between the two groups. Although animals fed HFD had similar serum triglyceride concentration to animals fed NTD, they had significantly higher phospholipid and total cholesterol concentrations than the NTD group. Furthermore, fecal lipid levels in the HFD group was significantly higher than those in the NTD group, suggesting that diet composition or energy density of the diet affects blood biochemistry. Although NTD-fed S. murinus had higher food ingestion than HFD-fed S. murinus, caloric intake remained almost the same. We speculated S. murinus may suppress obesity and control fat accumulation by controlling calorie intake. These results suggest that the obesity characteristics of S. murinus are not primarily due to dietary factors but to other mechanisms of regulation.

Obesity is the single greatest risk factor for the development of Type 2 diabetes mellitus (T2DM), with the prevalence of both dramatically increasing in recent years. These conditions are associated with medical complications such as hypertension, neuropathy and cardiovascular disease. Recent evidence also suggests a greater risk of developing dementia including Alzheimer's disease. The molecular mechanisms governing these changes remain obscure, although epidemiological evidence suggests that reduced insulin sensitivity (a characteristic of T2DM) is an independent risk factor for Alzheimer's disease. Here we examine the effects of diet-induced insulin resistance on cognitive ability in an animal model not predisposed to develop Alzheimer's pathology. Following 12 weeks on a high fat diet (45% of calories as crude fat) male Wistar rats were overweight and insulin resistant but not frankly diabetic. High fat fed animals were consistently poorer in all aspects of an operant based delayed matching to position task, yet were not impaired in spatial working memory as judged by the open field watermaze test. The cognitive deficit of the HF fed animals was most apparent when the task was switched from matching to non-matching to position, suggestive of an inability to change contingency. Performance in this task was negatively correlated with whole body insulin sensitivity but not weight gain. In conclusion this study has shown that insulin resistant animals exhibit impairments in an operant measure of behavioural flexibility which precede the development of diabetes.▶ High fat feeding (HFF) reduces peripheral insulin sensitivity in out-bred rats. ▶ HFF impairs an operant, but not a watermaze, delayed matching to position task. ▶ Effect of HFF is greater when the rule is switched from matching to non-matching. ▶ Cognitive deficit correlates with insulin sensitivity but not body weight.

For a number of years, coenzyme Q (CoQ10 in humans) was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in plasma, and extensively investigated its antioxidant role. These two functions constitute the basis on which research supporting the clinical use of CoQ10 is founded. Also at the inner mitochondrial membrane level, coenzyme Q is recognized as an obligatory co-factor for the function of uncoupling proteins and a modulator of the transition pore. Furthermore, recent data reveal that CoQ10 affects expression of genes involved in human cell signalling, metabolism, and transport and some of the effects of exogenously administered CoQ10 may be due to this property. Coenzyme Q is the only lipid soluble antioxidant synthesized endogenously. In its reduced form, CoQH2, ubiquinol, inhibits protein and DNA oxidation but it is the effect on lipid peroxidation that has been most deeply studied. Ubiquinol inhibits the peroxidation of cell membrane lipids and also that of lipoprotein lipids present in the circulation. Dietary supplementation with CoQ10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoproteins to the initiation of lipid peroxidation. Moreover, CoQ10 has a direct anti-atherogenic effect, which has been demonstrated in apolipoprotein E-deficient mice fed with a high-fat diet. In this model, supplementation with CoQ10 at pharmacological doses was capable of decreasing the absolute concentration of lipid hydroperoxides in atherosclerotic lesions and of minimizing the size of atherosclerotic lesions in the whole aorta. Whether these protective effects are only due to the antioxidant properties of coenzyme Q remains to be established; recent data point out that CoQ10 could have a direct effect on endothelial function. In patients with stable moderate CHF, oral CoQ10 supplementation was shown to ameliorate cardiac contractility and endothelial dysfunction. Recent data from our laboratory showed a strong correlation between endothelium bound extra cellular SOD (ecSOD) and flow-dependent endothelial-mediated dilation, a functional parameter commonly used as a biomarker of vascular function. The study also highlighted that supplementation with CoQ10 that significantly affects endothelium-bound ecSOD activity. Furthermore, we showed a significant correlation between increase in endothelial bound ecSOD activity and improvement in FMD after CoQ10 supplementation. The effect was more pronounced in patients with low basal values of ecSOD. Finally, we summarize the findings, also from our laboratory, on the implications of CoQ10 in seminal fluid integrity and sperm cell motility.

The major risk factors for non-alcoholic fatty liver disease (NAFLD) are obesity, insulin resistance and dyslipidemia. The cause for progression from the steatosis stage to the inflammatory condition (non-alcoholic steatohepatitis (NASH)) remains elusive at present. Aim of this study was to test whether the different stages of NAFLD as well as the associated metabolic abnormalities can be recreated in time in an overfed mouse model and study the mechanisms underlying the transition from steatosis to NASH. Male C57Bl/6J mice were subjected to continuous intragastric overfeeding with a high-fat liquid diet (HFLD) for different time periods. Mice fed a solid high-fat diet (HFD) ad libitum served as controls. Liver histology and metabolic characteristics of liver, white adipose tisue (WAT) and plasma were studied. Both HFD-fed and HFLD-overfed mice initially developed liver steatosis, but only the latter progressed in time to NASH. NASH coincided with obesity, hyperinsulinemia, loss of liver glycogen and hepatic endoplasmatic reticulum stress. Peroxisome proliferator-activated receptor γ (Pparγ), fibroblast growth factor 21 (Fgf21), fatty acid binding protein (Fabp) and fatty acid translocase (CD36) were induced exclusively in the livers of the HFLD-overfed mice. Inflammation, reduced adiponectin expression and altered expression of genes that influence adipogenic capacity were only observed in WAT of HFLD-overfed mice. this dietary mouse model displays the different stages and the metabolic settings often found in human NAFLD. Lipotoxicity due to compromised adipose tissue function is likely associated with the progression to NASH, but whether this is cause or consequence remains to be established.

Background and objectives: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by the accumulation of large amounts of fat in the hepatocytes. Given that atorvastatin is effective for treatment of NAFLD, the present study investigated effects of high-fat/fructose diet (HFFD) with atorvastatin on liver enzymes and lipid profile in a NAFLD rat model. Methods: Thirty-two male Wistar rats were divided into four groups: 1) normal control, 2) HFFD control, 3) HFFD + atorvastatin, and 4) normal + atorvastatin. The groups received HFFD for 15 weeks to induce hepatosteatosis. Atorvastatin was administrated at the dose of 10 mg/kg/day. Lipid profile and liver enzymes were measured after eight weeks of intervention. Results: Triglyceride, cholesterol, gamma-glutamyl transferase, and aspartate transaminase were significantly reduced in the HFFD + atorvastatin group compared with the HFFD control group. In addition, cholesterol, high-density lipoprotein, alkaline phosphatase, and gamma-glutamyl transferase were significantly increased in the normal + atorvastatin group compared with the normal control group. Low-density lipoprotein increased significantly in the HFFD + atorvastatin group and the normal + atorvastatin group compared with other groups. There was a significant difference in the alanine transaminase levels between the groups taking atorvastatin. In fact, alanine transaminase level was lowest in the normal + atorvastatin group. Conclusion: Atorvastatin improves the lipid profile and fatty liver and controls liver enzymes. Therefore, it can be used with caution to improve the lipid profile and reduce the complications of NAFLD.

Obesity: Dietary Intake, Sedentarism and Insulin Resistance. Obesity has been reported as a worldwide epidemic independent of economical and social conditions. The possible causes of increased mor- tality and morbidity associated with obesity have been focused by sev- eral studies that attempted to understand the syndrome X, one of the consequences of obesity. This syndrome is characterized by various metabolic