Contrasting metabolic effects of medium- versus long-chain fatty acids in skeletal muscle

Abstract

This article is available online at http://www.jlr.org arisen to a great extent from excess nutrient intake, especially in the form of fat. Intake of diets rich in long-chain fatty acids (LCFAs) (>C16 ), the most common fatty acid (FA) type in Western diets, is associated with disturbances in glucose homeostasis and insulin action ( 1, 2 ). Many mechanisms have been proposed to underpin the deleterious effects of LCFAs on metabolic health, including increased infl ammation, overactivation of stress-related pathways, and inappropriate lipid accumulation in nonadipose tissues ( 1, 3 ).Interestingly, not all dietary fats induce the same degree of metabolic dysfunction. Our group and others have shown that intake of equal-caloric diets rich in mediumchain fatty acids (MCFAs) (C8-C12) decreases adiposity ( 4-6 ), increases energy expenditure ( 7,8 ), and avoids many of the detrimental effects associated with LCFA intake. The increased energy expenditure suggests that FAs are funneled into oxidative versus storage pathways, and this has previously been suggested to be due to enhanced cellular uptake and entry of MCFAs into mitochondria (especially in the liver) for oxidation. In a recent study we showed that high-fat diets enriched with MCFAs caused a marked induction in mitochondrial oxidative capacity in muscle, over and above that induced by a LCFA high-fat diet, suggesting that enhanced myocellular oxidation of MCFAs might also be a key pathway for oxidative disposal of this class of FAs ( 8 ) Press, September 27, 2013 DOI 10.1194 Contrasting metabolic effects of medium-versus long-chain fatty acids in skeletal muscle Abbreviations: ASM, acid-soluble metabolite; CPT1, carnitine palmitoyl transferase 1; DAG, diacylglycerol; DHE, dihydroethidium; ETC, electron transport chain; FRL, free radical leak; GPx, glutathione peroxidase; GSK3 ␤ , glycogen synthase kinase 3 ␤ ; IRS1, insulin receptor substrate 1; LCFA, long-chain fatty acid; LOOH, lipid hydroperoxide; MCFA, medium-chain fatty acid; RER, respiratory exchange ratio; ROS, reactive oxygen species; SDH, succinate dehydrogenase; SOD2, superoxide dismutase 2; TAG, triacylglycerol; TBARS, thiobarbituric acid reactive substances; UCP3, uncoupling protein 3. Published, JLR Papers in

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Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

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