Coen 2013 Obesity (Silver Spring)
|Coen PM, Hames KC, Leachman EM, Delany JP, Ritov VB, Menshikova EV, Dubé JJ, Stefanovic-Racic M, Toledo FG, Goodpaster BH (2013) Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity. Obesity (Silver Spring) 21:2362-71.|
Abstract: OBJECTIVE: The link between a reduced capacity for skeletal muscle mitochondrial fatty acid oxidation (FAO) and lipotoxicity in human insulin resistance has been the subject of intense debate. The objective of this study was to investigate whether reduced FAO is associated with elevated acyl CoA, ceramide, and diacylglycerol (DAG) in severely obese insulin resistant subjects.
DESIGN AND METHODS: Muscle biopsies were conducted in lean (L, 22.6 ± 0.5 kg/m2, n = 8), Class I (CI, 32.1 ± 0.4 kg/m2, n = 7) and Class II&III obese (CII&III, 45.6 ± 1.1 kg/m2, n = 15) women for acyl CoA, sphingolipid and DAG profiling. Intramyocellular triglyceride (IMTG) content was determined by histology. FAO was assessed by incubating muscle homogenates with [1-C]palmitate and measuring CO2 production. Cardiolipin content was quantified as an index of mitochondrial content. Lipid metabolism proteins, DGAT1, PLIN5, and PNPLA2 were quantified in biopsy samples by western blot.
RESULTS: CII&III were more insulin resistant (HOMA-IR: 4.5 ± 0.5 vs. 1.1 ± 0.1, P < 0.001), and had lower FAO (∼58%, P = 0.007) and cardiolipin content (∼31%, P = 0.013) compared to L. IMTG was elevated in CI (P = 0.04) and CII&III (P = 0.04) compared to L. Sphingolipid content was higher in CII&III compared to L (13.6 ± 1.1 vs. 10.3 ± 0.5 pmol/mg, P = 0.031) whereas DAG content was not different among groups. DGAT1 was elevated in CII&III, and PLIN5 was elevated in CI compared to L.
CONCLUSION: Severe obesity is associated with reduced muscle oxidative capacity and occurs concomitantly with elevated IMTG, ceramide and insulin resistance. • Keywords: Insulin resistance
• O2k-Network Lab: US FL Orlando Goodpaster BH
Organism: Human Tissue;cell: Skeletal muscle Preparation: Homogenate
Regulation: Fatty acid