Dietary switch to Western diet induces hypothalamic adaptation associated with gut microbiota dysbiosis in rats

International audienceBackground: Early hyperphagia and hypothalamic inflammation encountered after Western diet (WD) are linked to rodent propensity to obesity. Inflammation in several brain structures has been associated with gut dysbiosis. Since gut microbiota is highly sensitive to dietary changes, we hypothesised that immediate gut microbiota adaptation to WD in rats is involved in inflammation-related hypothalamic modifications. Methods: We evaluated short-term impact of WD consumption (2 h, 1, 2 and 4 days) on hypothalamic metabolome and caecal microbiota composition and metabolome. Data integration analyses were performed to uncover potential relationships among these three datasets. Finally, changes in hypothalamic gene expression in absence of gut microbiota were evaluated in germ-free rats fed WD for 2 days. Results: WD quickly and profoundly affected the levels of several hypothalamic metabolites, especially oxidative stress markers. In parallel, WD consumption reduced caecal microbiota diversity, modified its composition towards pro-inflammatory profile and changed caecal metabolome. Data integration identified strong correlations between gut microbiota sub-networks, unidentified caecal metabolites and hypothalamic oxidative stress metabolites. Germ-free rats displayed reduced energy intake and no changes in redox homoeostasis machinery expression or pro-inflammatory cytokines after 2 days of WD, in contrast to conventional rats, which exhibited increased SOD2, GLRX and IL-6 mRNA levels. Conclusion: A potentially pro-inflammatory gut microbiota and an early hypothalamic oxidative stress appear shortly after WD introduction. Tripartite data integration highlighted putative links between gut microbiota sub-networks and hypothalamic oxidative stress. Together with the absence of hypothalamic modifications in germ-free rats, this strongly suggests the involvement of the microbiota-hypothalamus axis in rat adaptation to WD introduction and in energy homoeostasis regulation

Energy restriction only slightly influences protein metabolism in obese rats, whatever the level of protein and its source in the diet

International audienceBACKGROUND: High protein (HP) diets during energy restriction have been studied extensively regarding their ability to reduce body fat and preserve lean body mass, but little is known about their effects on protein metabolism in lean tissues. OBJECTIVE: To determine the effects of energy restriction and protein intake on protein anabolism and catabolism in rats. METHODS: For 5 weeks, 56 male Wistar rats were fed an obesity induction (OI) diet. They were then subjected to a 40% energy restriction using the OI diet or a balanced HP diet for 3 weeks, whereas a control group was fed the OI diet ad libitum (n ¼ 8 per group). HP-restricted rats were divided into five groups differing only in terms of their protein source: total milk proteins, casein (C), whey (W), a mix of 50% C and W, and soy (n ¼ 8). The animals were then killed in the postprandial state and their body composition was determined. Protein synthesis rates were determined in the liver, gastrocnemius and kidney using a subcutaneous 13 C valine flooding dose. mRNA levels were measured for key enzymes involved in the three proteolysis pathways. RESULTS: Energy restriction, but not diet composition, impacted weight loss and adiposity, whereas lean tissue mass (except in the kidney) was not influenced by diet composition. Levels of neoglucogenic amino acids tended to fall under energy restriction (Po0.06) but this was reversed by a high level of protein. The postprandial protein synthesis rates in different organs were similar in all groups. By contrast, mRNA levels encoding proteolytic enzymes rose under energy restriction in the muscle and kidney, but this was counteracted by a HP level. CONCLUSIONS: In adult obese rats, energy restriction but not diet composition affected fat pads and had little impact on protein metabolism, despite marked effects on proteolysis in the kidney and muscle. INTRODUCTION Weight management strategies are designed to reduce body fat while causing no major reduction in lean tissue. The different strategies proposed 1,2 involve varying levels of energy restriction and modifications to the energy nutrient content of diets, such as limiting the consumption of fat or carbohydrate (CHO) and increasing the protein content. 3,4 Proteins have been the focus of particular study because of their satiating effect that might both reduce energy intake 5 and increase subject compliance with a diet. 6,7 In addition, a protein-rich diet may minimize the loss of lean body mass that is observed under a low-calorie diet. 8,9 The type of protein source may also exert an influence, as reported in rodent models. 10,11 The effects of energy restriction on anabolic and catabolic fluxes are poorly understood and the findings available, which differ regarding numerous parameters (model, duration, degree of restrictions), are not comparable. In humans, one study recently showed that muscle protein synthesis was decreased after moderate energy restriction. 12 Other data have been obtained in rats and revealed contrasting effects of energy restriction on muscle protein anabolism, depending the type of muscle (soleus