The gut and the liver are the key organs in nutrient absorption and metabolism. The gut adapts to the composition of the diet by direct substrate effects in addition to neural and endocrine mechanisms. These adaptations include the intestinal mucosa and the gut microbiota. Depending on the diet, the profile of nutrients, metabolites, gut peptides and other mediators released from the gut can be modified. The liver is the first organ which comes into contact with the molecules arising from gut digestion. Nutrients and metabolites delivered from the intestine are sensed in the liver and trigger an adaptation of liver function to improve their hepatic processing. These processes together with neural and endocrine mechanisms regulate liver function and exert a direct or indirect feedback control of gut function. This project aims to evaluate the consequences of increasing protein in a context of either a high carbohydrate or a high fat diet on the adaptation of the gut-liver axis in rodents. A high carbohydrate diet induces hepatic steatosis through the stimulation of hepatic lipogenesis. In contrast, a high fat diet is believed to induce liver metabolic dysfunction and steatosis through dietary fat accumulation but also by inducing gut bacterial overgrowth and endotoxemia leading to a pro-inflammatory state in the gut-liver axis. In order to evaluate the effect of protein in both situations, animals are adapted for several weeks to 4 diets including a control high carbohydrate diet, a high protein-low fat diet, a high fat diet and a high fat-high protein diet. The analyses include gene expression and metabolic phenotyping in the gut mucosa and liver, characterisation of the microbiota, gut, liver and peripheral inflammatory state, hepatic lipogenesis and steatosis, glucose homeostasis, protein turnover in tissues, energy expenditure, substrate oxidation, body composition and food intake behaviour.
|Effective start/end date||6/10/10 → 5/10/13|
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.