Skeletal Muscle Lipid Metabolism in Exercise and Insulin Resistance

Abstract

Lipids as fuel for energy provision originate from different sources: albumin-bound long-chain fatty acids (LCFA) in the blood plasma, circulating very-low-density lipoproteins-triacylglycerols (VLDL-TG), fatty acids from triacylglycerol located in the muscle cell (IMTG), and possibly fatty acids liberated from adipose tissue adhering to the muscle cells. The regulation of utilization of the different lipid sources in skeletal muscle during exercise is reviewed, and the influence of diet, training, and gender is discussed. Major points deliberated are the methods utilized to measure uptake and oxidation of LCFA during exercise in humans. The role of the various lipid-binding proteins in transmembrane and cytosolic transport of lipids is considered as well as regulation of lipid entry into the mitochondria, focusing on the putative role of AMP-activated protein kinase (AMPK), acetyl CoA carboxylase (ACC), and carnitine during exercise. The possible contribution to fuel provision during exercise of circulating VLDL-TG as well as the role of IMTG is discussed from a methodological point of view. The contribution of IMTG for energy provision may not be large, covering approximately 10% of total energy provision during fasting exercise in male subjects, whereas in females, IMTG may cover a larger proportion of energy delivery. Molecular mechanisms involved in breakdown of IMTG during exercise are also considered focusing on hormone-sensitive lipase (HSL). Finally, the role of lipids in development of insulin resistance in skeletal muscle, including possible molecular mechanisms involved, is discussed.

Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity

“…Since the present study included an endurancetrained group, this is consistent with data from Goodpaster and colleagues [31], and is in line with previous studies that did not find coupling when muscle triacylglycerol was measured biochemically in samples of muscle tissue [3,32]. It is generally thought that excess intramyocellular lipid storage results in decreased insulin sensitivity because an increased fatty acid precursor supply leads to increased concentrations of one or more of the lipid intermediates: diacylglycerol, long-chain fatty acyl-CoA or ceramide [9,33,34].…”

Intramyocellular triglyceride content in man, influence of sex, obesity and glycaemic control

“…Neutral fat in muscle plays an important role as oxidative substrate during and following physical activity (1). Athletes and well-trained individuals possess a high concentration of intramyocellular triglyceride (IMTG) (2), which after a training bout may be reduced by 20-30% during the recovery period where muscle glycogen depots build up (3).…”

Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

“…To meet these demands, acute exercise is associated with marked changes in skeletal muscle activity of key transporters and enzymes involved in glucose and fatty acid transport and oxidation (1). Much of the regulation occurs via allosteric regulation and covalent modification of rate-limiting enzymes.…”