Association of Muscle Lipidomic Profile with High-fat Diet-induced Insulin Resistance Across Five Mouse Strains

Different mouse strains exhibit variation in their inherent propensities to develop metabolic disease. We recently showed that C57BL6, 129X1, DBA/2 and FVB/N mice are all susceptible to high-fat diet-induced glucose intolerance, while BALB/c mice are relatively protected, despite changes in many factors linked with insulin resistance. One parameter strongly linked with insulin resistance is ectopic lipid accumulation, especially metabolically active ceramides and diacylglycerols (DAG). This study examined diet-induced changes in the skeletal muscle lipidome across these five mouse strains. High-fat feeding increased total muscle triacylglycerol (TAG) content, with elevations in similar triacylglycerol species observed for all strains. There were also generally consistent changes across strains in the abundance of different phospholipid (PL) classes and the fatty acid profile of phospholipid molecular species, with the exception being a strain-specific difference in phospholipid species containing two polyunsaturated fatty acyl chains in BALB/c mice (i.e. a diet-induced decrease in the other four strains, but no change in BALB/c mice). In contrast to TAG and PL, the high-fat diet had a minor influence on DAG and ceramide species across all strains. These results suggest that widespread alterations in muscle lipids are unlikely a major contributors to the favourable metabolic profile of BALB/c mice and rather there is a relatively conserved high-fat diet response in muscle of most mouse strains.