Observational cross-sectional studies have described associations between the saturation status of both phospholipids and diacylglycerol (DAG) with insulin sensitivity (IS) of skeletal muscle. The purpose of this study was to test the hypothesis that diet-induced weight loss and exercise reduce intramyocellular lipid saturation and that this is associated with improved IS. We studied forty subjects who competed a randomized controlled trial (RCT) consisting of 6 months of either Health Education Control (CON: n=13 5M/8F), Diet-induced weight-loss only (DIWL: n=13 5M/8F), or Weight-loss and Exercise (WLEX: n=14 6M/9F). DIWL and WLEX subjects had a goal of 10% weight-loss through calorie restriction. Hyperinsulinemic euglycemic clamps were employed to measure IS, and muscle biopsies were obtained to quantify intramyocellular lipids by mass spectrometry. The DIWL and WLEX groups both lost a significant amount of weight compared to CON (DIWL: -6.4%, WLEX: -11.3%, CON: -2.5%, P<0.05). IS measured as the glucose infusion rate required to maintain euglycemia during the clamp increased in the DIWL and WLEX groups compared to the control group (DIWL: 1.0, WLEX: 2.7, CON: 0.6 mg/FFMkg/min, P<0.05). Total phosphatidylethanolamine (PE), phosphatidylcholine (PC), diacylglycerols (DAG) did not significantly change following intervention (P>0.05). However, there were trends for unsaturated PE and PC species to increase in the WLEX only and saturated DAG and ceramide species to be reduced in both the DIWL and WLEX group. The increase in unsaturation of PE and PC were associated with improvements in IS (PE: P=0.047, r=0.35; PC: P=0.072, r=0.32) and the decrease in saturation of DAG was associated with improvements in IS (P=0.044, r=-0.36).
In conclusion, weight-loss and exercise increase unsaturated PE and PC species, and reduce saturated DAG species, which are related to improved IS within skeletal muscle.
R. Standley: None. P.M. Coen: None. B.H. Goodpaster: None.