Grant: Project Grant

Poor dietary and lifestyle habits are implicated in the development of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). Dairy products have been suggested to reduce T2D risk and fermented dairy, notably yogurt, has received particular attention. Human studies reported that yogurt consumption is inversely associated with body weight gain and T2D incidence. However, the mechanisms underlying the beneficial effects of yogurt consumption remain unknown. We recently found that yogurt intake changes the gut flora (also known as gut microbiota) and prevents T2D and reduces liver fat in high-fat fed mice. We further showed that yogurt's beneficial impact is correlated with higher levels of hydroxylated metabolites (BCHA) of branched chain amino acids (BCAA). These BCHA are not present in milk but generated during dairy protein fermentation and concentrated in yogurt. These data suggest that BCHA are novel metabolic regulators and potential mediators of yogurt's health effects. We hypothesize that altered metabolism of BCAA to BCHA is a feature of T2D and that stimulating host BCHA production and supplementing yogurt with BCHA can alleviate T2D and NAFLD in animal models and human subjects. This working hypothesis will be tested through pursuing the following objectives Obj 1) To determine the contribution of altered GM and host tissue mechanisms to blunted BCHA production in obese mice with insulin resistance and NAFLD. Obj 2) To evaluate whether increasing BCHA availability can alleviate T2D and NAFLD in obese mice. Obj 3) To determine whether increasing BCHA content enhances yogurt's health effect in human subjects with T2D ans NAFLD by reducing insulin resistance, fasting glycemia and liver fat content. These studies will shed new light on the emerging understanding of how yogurt can reduce the increasing risk of T2D and NAFLD in the Canadian population.