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Exercise counteracts lipotoxicity by improving lipid turnover and lipid droplet quality.

Exercise counteracts lipotoxicity by improving lipid turnover and lipid droplet quality.
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Zacharewicz E, Hesselink MKC, Schrauwen P,


Zacharewicz E, Hesselink MKC, Schrauwen P, (click to view)

Zacharewicz E, Hesselink MKC, Schrauwen P,

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Journal of internal medicine 2018 01 13() doi 10.1111/joim.12729
Abstract

The incidence of obesity and metabolic disease, such as type 2 diabetes mellitus (T2D), are rising globally. Dietary lipid over-supply leads to lipid accumulation at ectopic sites, such as skeletal muscle. Ectopic lipid storage is highly correlated with insulin resistance and T2D, likely due to a loss of metabolic flexibility – the capacity to switch between fat and glucose oxidation upon insulin stimulation – and cellular dysfunction because of lipotoxicity. However, muscle lipid levels are also elevated in endurance trained athletes, presenting a paradoxical phenotype of increased intramuscular lipids along with high insulin sensitivity – the "athletes’ paradox". This review focusses on recent human data to characterise intramuscular lipid species in order to elucidate some of the underlying mechanisms driving skeletal muscle lipotoxicity. There is evidence that lipotoxicity is characterised by an increase in bioactive lipid species, such as ceramide. The athletes’ paradox supports the notion that regular physical exercise has health benefits that might originate from the alleviation of lipotoxicity. Indeed, exercise training alleviates intramuscular ceramide content in obese individuals without a necessary decrease in ectopic lipid storage. Furthermore, evidence shows that exercise training elevates markers of lipid droplet dynamics such as the PLIN proteins, and triglyceride lipases ATGL and HSL, as well as mitochondrial efficiency, potentially explaining the improved lipid turnover and a reduction in the accumulation of lipotoxic intermediates observed with the athelets’ paradox. This article is protected by copyright. All rights reserved.

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