Grant: Project Grant

Obesity and type 2 diabetes (T2D) are chronic diseases that affect millions of people worldwide. A variety of strategies have been proposed to offset obesity and T2D but the focus has been mainly to reduce fat and carbohydrates. However, we recently discovered that dietary proteins are key nutrients that contribute to fat-induced obesity, insulin resistance and T2D. The dietary protein effects were associated with major changes liver lipid metabolism. However, the molecular mechanisms underlying these effects remain unknown. In this new project we will design further studies to delinate potential mechanims by which dietary proteins dictates liver function and insulin sensitivity. Research objectives are : 1) To assess whether dietary proteins can change the function of mitochondria in liver to alter insulin action through altering the urea cycle in obese mice; 2) To assess whether urea cycle activation by dietary proteins modulates insulin sensitivity in liver by promoting inflammation; 3) To determine whether dietary proteins affect liver health through changing the production of trimethylamine oxide, a by-product of meat protein metabolism, in obese mice ; and 4) Determine whether these parameters measured in obese mice also changed in obese persons that are pre-diabetic or have type 2 diabetes. Studies will be performed in both male and female mice, using dietary and genetic mouse models. Key findings will also be validated in human using plasma and liver biopsies from both men and women with obesity. This research represents a major leap forward in understanding how specific protein sources or their components impact on obesity and diabetes, and may help define novel dietary strategies for preventing diabetes.