Intestinal tract helps control weight
Scientists have identified an unexpected intestinal bacterial interaction potentially affecting the human development of obesity and diabetes type 2.
The team at Louvain Drug Research Institute, Université Catholique de Louvain (UCL) led by Patrice D. Cani PhD, discovered how the intestinal immune system helps control energy metabolism. It found that inactivation of a protein called MyD88 in the cells lining the intestinal track of diabetic mice, allowed those mice to gain more energy from their food.
Disabling the protein MyD88 slowed down development of diabetes by limiting the development of adipose (fat) tissue.
Reducing the harmful inflammation of obesity strengthened the function of the intestine as a barrier to limit inappropriate transit of bacteria through the intestines and into the mouse.
Specifically, the team found inactivation of MyD88 seems to strengthen the intestinal barrier and limit much of the transit of bacteria from our intestines into our body.
Researchers also found they could transfer (by grafting) intestinal cells with MyD88 protein into the intestines of mice with the MyD88 deletion — making it possible for those mice to lose weight even when they were already obese and diabetic.
The observation was made that during consumption of a fatty diet, the intestinal immune system played an important role in regulating fat storage by modifications to intestinal bacteria.
The discovery is published in the scientific journal Nature Communications, and confirms the involvement of intestinal bacteria in the development of obesity. More importantly, the work provides new therapeutic possibilities for treating obesity and type 2 diabetes.
Obesity is associated with a cluster of metabolic disorders, low-grade inflammation and altered gut microbiota. Whether host metabolism is controlled by intestinal innate immune system and the gut microbiota is unknown. Here we report that inducible intestinal epithelial cell-specific deletion of ?MyD88 partially protects against diet-induced obesity, diabetes and inflammation. This is associated with increased energy expenditure, an improved ?glucose homeostasis, reduced hepatic steatosis, fat mass and inflammation. Protection is transferred following gut microbiota transplantation to germ-free recipients. We also demonstrate that intestinal epithelial ?MyD88 deletion increases anti-inflammatory endocannabinoids, restores antimicrobial peptides production and increases intestinal regulatory T cells during diet-induced obesity. Targeting ?MyD88 after the onset of obesity reduces fat mass and inflammation. Our work thus identifies intestinal epithelial ?MyD88 as a sensor changing host metabolism according to the nutritional status and we show that targeting intestinal epithelial ?MyD88 constitutes a putative therapeutic target for obesity and related disorders.
Everard A et al. Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status. Nature Communications. 5:5648, DOI: 10.1038/ncomms6648.
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