Linoleic and α‐Linolenic Acid Prevent Insulin Resistance in Obese Zucker Rats but have Different Impacts on Skeletal Muscle Metabolism

Abstract

The use of long‐chain polyunsaturated fatty acids (LC‐PUFAs) to prevent the development of insulin resistance (IR) has recently gained considerable interest. However, the roles of essential PUFAs (i.e., linoleic acid, LA; α‐linolenic acid, ALA) remain poorly understood. We investigated the efficacy of diets enriched with either LA or ALA on preventing IR in obese Zucker rats. After the 12‐wk intervention, both LA‐ and ALA‐enriched diets protected against IR compared to obese control animals. The maintenance of whole‐body glucose homeostasis was linked to the preservation of muscle‐specific insulin sensitivity. LA and ALA differentially regulated markers of skeletal muscle mitochondrial content, respiratory function and H2O2 emission. However, both LA and ALA prevented increases in 4‐HNE content (i.e., a marker of oxidative stress) compared to obese control animals. Collectively, the protective effects of LA and ALA appear independent of mitochondrial bioenergetics, but may involve improvements in oxidative stress. Subsequent lipid profiling in skeletal muscle by gas chromatography revealed that LA and ALA increased omega‐6 and omega‐3 PUFA content, as expected. However, diacylglycerol (DAG) and ceramide accumulation was similar between obese control, LA and ALA groups; suggesting that preservation of skeletal muscle insulin sensitivity occurred independent of changes in reactive lipid content. Overall, LA and ALA are efficacious in preventing obesity‐related IR, but further work is necessary to elucidate the mechanism(s) of action.Grant Funding Source: Supported by OMAFRA