Insulin‐resistant female rat skeletal muscles display diacylglycerol‐mediated protein kinase C activation and inflammation without ceramide accumulation

Abstract

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One size does not fit all: insight into skeletal muscle insulin resistance in female rats fed a high‐fat sucrose‐enriched diet

“…Surprisingly, Jani et al. (2023) discovered there was no significant difference in ceramide content with HFS feeding, as ceramide content was previously shown to be increased in insulin‐resistance models. Further, mRNA analysis showed a significant increase in Dgat2 gene expression in all muscle fibres, whereas no changes in Dgat1 gene expression were detected.…”

“…Therefore, it is plausible that fibre type distribution plays a key role in insulin responsiveness, and that the investigation by Jani et al. (2023) supplies new mechanistic insight to support this idea.…”

“…A recently published article in The Journal of Physiology by Jani et al. (2023) set out to understand potential mechanisms underlying higher peripheral insulin sensitivity in females.…”

“…In the study by Jani et al. (2023), female Wistar rats were fed ad libitum either a standard chow (SC) or a diet high in fat and sucrose (HFS) for a total of 8 weeks. A non‐fasting glucose tolerance test completed at the end of the dietary intervention showed HFS feeding caused significant hyperglycaemia and hyperinsulinaemia, suggestive of insulin resistance.…”

High‐fat high‐sucrose diet‐induced skeletal muscle insulin resistance in female rats: a new soprano in the DAG chorus

“…For decades, the role of lipid moietiesthe most discussed being diacylglycerols (DAGs) and ceramides -in causing diet-induced insulin resistance has been debated (Nicholson et al, 2022;Petersen & Shulman, 2018). In a recent edition of the Journal of Physiology, Jani et al (2023) add to this chorus by explaining that a high-fat sucrose-enriched (HFS) diet induces insulin resistance in female oxidative and glycolytic skeletal muscles, and results in an increase in the levels of triacylglycerol (TAG) and DAGs in the soleus and extensor digitorum longus muscles, and markers of inflammation and TAG in the epitrochlearis muscle. However, differences in skeletal muscle ceramide concentrations were not observed.…”