Xiong Su, Ph.D.
Project Overview:
Obesity is an important risk factor for developing type 2 diabetes, which is caused by insulin resistance in conjunction with inadequate pancreatic function. Obesity is also associated with a constellation of health complications, including inflammation, heart disease and cancer. Thus, it is important to identify specific biomarkers which predict risk and progression of obesity-associated metabolic pathology. The ideal biomarkers should be able to inform on activities of multiple metabolic pathways. Our preliminary data suggest that monomethyl branched chain fatty acids are such potential candidates.
In this study, we will perform detailed lipid analysis in human adipose and plasma samples to explore the obesity-related changes of these little-studied fatty acids. The functions of the specific fatty acids will be further investigated in mice. We believe that our study will provide important information to identify novel and more integrative biomarkers which predict risk of obesity-associated metabolic disease.
Final Report:
Monomethyl branched chain fatty acids (mmBCFAs) are commonly found in many organisms and recent studies suggest that they play critical roles in regulating specific lipid metabolism and cellular signaling pathways. However, their physiological role and metabolic regulation are unknown. mmBCFAs are de novo synthesized from branched chain acyl CoA precursors derived from branched chain amino acids (BCAAs). Our study demonstrated that mmBCFAs are present in human adipose tissues and their levels are significantly lower in tissues from obese subjects with insulin resistance as compared to lean subjects. Moreover, our study explored potential mechanisms leading to the regulation of mmBCFA synthesis in obesity and its contribution to human insulin resistance. Collectively, our results suggest that mmBCFAs and the more complex lipid species containing those FAs may represent novel and more integrative biomarkers for predicting risk of obesity‐associated metabolic dysfunction.
