1a.Objectives (from AD-416):
The ability of body tissues to efficiently convert nutrients to energy at the cellular site of this process (mitochondria) is impaired in several conditions of poor metabolic health. These include type 2 diabetes mellitus (T2DM) and pre-diabetes (the condition of increasingly poor control of blood sugar by the pancreatic hormone insulin, but prior to clinically high blood sugar levels). The exact mechanisms that drive this sub-optimal metabolism remain controversial, but the body of literature indicates that reduced numbers of mitochondria along with inefficiencies within each mitochondrion take place. The investigators have proposed that activity of the key enzyme of tissue breakdown of branched-chain amino acids (BCAAs) is limited under these conditions, contributing to poor metabolic control. Provision of diets rich in BCAA, such as dairy, should trigger increased expression and activity of this enzyme (branched chain alpha-ketoacid dehydrogenase, BCKD), supported by historic literature. It is hypothesized that an increase in BCKD by dairy or BCAAs will improve mitochondrial health in fat, muscle and other tissues. The proposal addresses this question using unique analytical and biological tools.
1b.Approach (from AD-416):
A comprehensive analytical chemistry assay measuring >400 metabolites will be employed to test samples derived from the following project aim: Determine if increased intake of diets rich in dairy or dairy components modify blood biomarkers reflective of improved mitochondrial efficiency and health in humans.
This research relates to objective 3 of the inhouse project, “Determine mechanisms underlying the regulation of body weight and disorders associated with obesity, by examining hormonal, neuronal, and metabolite pathways linking adipose and non-adipose tissues, and characterizing tissue-specific inflammation in humans, cells, and animal models". Samples from all 3 human studies have been analyzed for metabolomics profiles, and data are being analyzed in preparation for manuscript submission anticipated in FY2014. This is the final report for this project.