Hypothalamic inflammation and the development of an obese phenotype induced by high-fat diet consumption is exacerbated in alpha7 nicotinic cholinergic receptor knockout mice.

Hypothalamic inflammation and metabolic changes resulting from the consumption of high-fat diets have been linked to low grade inflammation and obesity. Inflammation impairs the hypothalamic expression of α7 nicotinic acetylcholine receptor (α7nAChR). The α7nAChR is described as the main component of the anti-inflammatory cholinergic pathway in different inflammation models. To assess whether the reduction in α7nAChR expression exacerbates hypothalamic inflammation induced by a high-fat diet (HFD), were used male and female global α7nAChR knockout mouse line in normal or high-fat diet for 4 weeks. Body weight gain, adiposity, glucose homeostasis, hypothalamic inflammation, food intake, and energy expenditure were evaluated. Insulin sensitivity was evaluated in neuronal cell culture. Consumption of an HFD for 4 weeks resulted in body weight gain and adiposity in male Chrna7-/- mice and the hypothalamus of male Chrna7-/- mice showed neuroinflammatory markers, with increased gene expression of pro-inflammatory cytokines and dysregulation in the nuclear factor kappa B pathway. Moreover, male Chrna7-/- mice consuming an HFD showed alterations in glucose homeostasis and serum of Chrna7-/- mice that consumed an HFD impaired insulin signalling in neuronal cell culture experiments. In general, female Chrna7-/- mice that consumed an HFD did not show the phenotypic and molecular changes found in male mice, indicating that there is sexual dimorphism in the analysed parameters. Thus, receptor deletion resulted in increased susceptibility to hypothalamic inflammation and metabolic damage associated with HFD consumption in male mice.

High-fat diet and fructose drink introduced after weaning rats, induces a better human obesity model than very high-fat diet.

In the present study, we associated a high-fat diet (HF group: 45% kcal from lipids) or very high-fat (VHF group: 60% kcal from lipids) diet with a fructose drink (10% fructose) for hydration. Normal rat chow that received the control diet (content 16.3% kcal from lipid-AIN93G) and water. The treatments were introduced soon after weaning and were administered for 70 days. We aimed to compare HF and VHF groups and find which acts as a better model mimicking human obesity. Body mass gain, final body weight, adipocyte area in inguinal depots, visceral and subcutaneous adipose depots, serum triacylglycerol, and VLDL-c were all higher in the HF group, followed by the VHF group, compared to the C group. Only the HF group showed hyperinsulinemia and hyperleptinemia and higher total caloric intake, Lee index, HOMA2-IR, and total cholesterol. Serum TNF-α and IL-6 levels were lower in the HF and VHF groups than in the C group at the end for 70 days. In Summary, the HF (45%) diet administered with fructose induced a higher similarity of metabolic and hormonal alterations associated with human obesity. PRACTICAL APPLICATIONS: High intake of lipids with sugary drinks has been associated with obesity and its comorbidities. Although a diet with 45% or 60% of lipids is considered hyperlipidic, they are different in their effects on eating behavior and also probably from a metabolic point of view. Common sense is that the reduction in intake of lipids is favorable to health. Our study shows that this is not wholly true, and this information contributes to the guidelines for the treatment of obesity. In addition, the scientific literature on the subject has shown the most diverse results and also the use of experimental models with few similarities with human obesity. Our findings can contribute as a good model of obesity initiated during childhood to investigate possible using nutritional strategies, or the adoption of ergogenic nutritional resources in future studies, for example.