Modulating Physiologic Effects Of Phospholipid Metabolism In Obesity And Diabetes; AIM 4: Composition and Function of Sarcoplasmic Reticulum in Persons With the Metabolic Syndrome

The Comp-SR study explores the role of lipid metabolism in key metabolic pathways in skeletal muscle. It is a translation of previous research done in mice studying the effects and functions of certain key enzymes involved in lipid metabolism found to be associated with insulin resistance. These enzymes are fatty acid synthase (FAS), choline/ethanolamine phosphotransferase 1 (CEPT1) and sarcoplasmic-endoplasmic reticulum ATPase (SERCA). Based on the investigators research, it appears that the activity and function of these enzymes determines the ratio of certain phospholipids in the sarcoplasmic reticulum (SR), namely phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Furthermore, the investigators have found that the ratio of these phospholipids correlates with the mouse's sensitivity to insulin.

Based on the muscle biopsies of four healthy persons, it was found that human muscle contains similar phospholipids and phospholipid ratios to mice. It is hypothesized that these phospholipid signatures may be predictive of the metabolic status of humans as well. The specific aims of this study are to determine if the composition and function of the sarcoplasmic reticulum is altered in persons with the metabolic syndrome compared to lean controls. This knowledge could provide new understanding of impediments to effective therapy, novel biomarkers of disease progression, and innovative treatment targets for diabetes.