Role of fatty acids in the transition from anaerobic to aerobic metabolism in skeletal muscle during exercise

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.

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Role of stearoyl-CoA desaturase-1 in skeletal muscle function and metabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00268.2013 ◽

2013 ◽

Vol 305 (7) ◽

pp. E767-E775 ◽

Cited By ~ 17

Author(s):

Alexis D. Stamatikos ◽

Chad M. Paton

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Lipid Metabolism ◽

Saturated Fatty Acids ◽

Monounsaturated Fatty Acids ◽

Skeletal Muscle Function ◽

Skeletal Muscle Lipid ◽

Stearoyl Coa Desaturase ◽

Scd1 Expression

Stearoyl-CoA desaturase-1 (SCD1) converts saturated fatty acids (SFA) into monounsaturated fatty acids and is necessary for proper liver, adipose tissue, and skeletal muscle lipid metabolism. While there is a wealth of information regarding SCD1 expression in the liver, research on its effect in skeletal muscle is scarce. Furthermore, the majority of information about its role is derived from global knockout mice, which are known to be hypermetabolic and fail to accumulate SCD1's substrate, SFA. We now know that SCD1 expression is important in regulating lipid bilayer fluidity, increasing triglyceride formation, and enabling lipogenesis and may protect against SFA-induced lipotoxicity. Exercise has been shown to increase SCD1 expression, which may contribute to an increase in intramyocellular triglyceride at the expense of free fatty acids and diacylglycerol. This review is intended to define the role of SCD1 in skeletal muscle and discuss the potential benefits of its activity in the context of lipid metabolism, insulin sensitivity, exercise training, and obesity.

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Elevated Free Fatty Acids Attenuate the Insulin-Induced Suppression of PDK4 Gene Expression in Human Skeletal Muscle: Potential Role of Intramuscular Long-Chain Acyl-Coenzyme A

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1104 ◽

2007 ◽

Vol 92 (10) ◽

pp. 3967-3972 ◽

Cited By ~ 53

Author(s):

Kostas Tsintzas ◽

Kamal Chokkalingam ◽

Kirsty Jewell ◽

Luke Norton ◽

Ian A. Macdonald ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Fatty Acids ◽

Human Skeletal Muscle ◽

Potential Role ◽

Chain Acyl ◽

Acyl Coenzyme A ◽

Long Chain ◽

Muscle Potential

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Metabolic cross talk between the colon and the periphery: implications for insulin sensitivity

Proceedings of The Nutrition Society ◽

10.1017/s0029665107005617 ◽

2007 ◽

Vol 66 (3) ◽

pp. 351-361 ◽

Cited By ~ 51

Author(s):

M. Denise Robertson

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Insulin Sensitivity ◽

Disease Risk ◽

Metabolic Adaptation ◽

Surgical Removal ◽

Colonic Tissue ◽

Peripheral Tissues

Until recently, a glance at a standard undergraduate textbook would have given the impression that the colon was merely a storage organ for faeces and maybe something about the absorption of electrolytes and water. In reality, the colon is a highly-metabolically-active organ, the function of which has implications not only for the remainder of the digestive tract, but also for peripheral organs such as adipose tissue (AT), liver and skeletal muscle. The present review focuses on two distinct but complementary areas: (1) the metabolic adaptation that occurs following surgical removal of colonic tissue; (2) the effect of modulating the colonin situin terms of postprandial metabolism, insulin sensitivity and disease risk. Work in these two areas points to the colon being important in modulating normal tissue insulin sensitivity. The role of fatty acids is central to the insulin sensitivity hypothesis. AT acts as a daily ‘buffer’ for fatty acids. However, following colonic resection there is an apparent change in AT function. There is an increase in the AT lipolysis rate, resulting in the release of excess fatty acids into the circulation and consequently the take up of excess fatty acids into skeletal muscle. This resultant increase in either storage of lipid or its oxidation would result in a reduction in insulin sensitivity. The insulin-sensitising effects of high-fibre diets are also related to changes in AT function and fatty acid metabolism, but manipulating colonic tissuein situallows the mechanisms to be elucidated. This research area is an exciting one, involving the potential role of SCFA (the absorbed by-products of colonic bacterial fermentation) acting directly on peripheral tissues, following the recent identification of G-protein-coupled receptors specific for these ligands.

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Role of Exercise-Induced Calmodulin Protein Kinase (CaMK)II Activation in the Regulation of Omega-6 Fatty Acids and Lipid Metabolism Genes in Rat Skeletal Muscle

Physiological Research ◽

10.33549/physiolres.933509 ◽

2017 ◽

pp. 969-977 ◽

Cited By ~ 1

Author(s):

J. S. JOSEPH ◽

A. O. AYELESO ◽

E. MUKWEVHO

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Fatty Acids ◽

Lipid Metabolism ◽

Rat Skeletal Muscle ◽

Exercise Induced ◽

Diabetes And Obesity ◽

Camkii Activation

Activation of calmodulin dependent protein kinase (CaMK)II by exercise is beneficial in controlling membrane lipids associated with type 2 diabetes and obesity. Regulation of lipid metabolism is crucial in the improvement of type 2 diabetes and obesity associated symptoms. The role of CaMKII in membrane associated lipid metabolism was the focus of this study. Five to six weeks old male Wistar rats were used in this study. GC×GC-TOFMS technique was used to determine the levels of polyunsaturated fatty acids (linoleic acid, arachidonic acid and 11,14-eicosadienoic acid). Carnitine palmitoyltransferase (Cpt-1) and acetyl-CoA carboxylase (Acc-1) genes expression were assessed using quantitative real time PCR (qPCR). From the results, CaMKII activation by exercise increased the levels of arachidonic acid and 11,14-eicosadienoic acid while a decrease in the level of linolenic acid was observed in the skeletal muscle. The results indicated that exercise-induced CaMKII activation increased CPT-1 expression and decreased ACC-1 expression in rat skeletal muscle. All the observed increases with activation of CaMKII by exercise were aborted when KN93, an inhibitor of CaMKII was injected in exercising rats. This study demonstrated that CaMKII activation by exercise regulated lipid metabolism. This study suggests that CaMKII can be a vital target of therapeutic approach in the management of diseases such as type 2 diabetes and obesity that have increased to epidemic proportions recently.

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The role of monounsaturated fatty acids in regulation of insulin signaling in skeletal muscle

Chemistry and Physics of Lipids ◽

10.1016/j.chemphyslip.2011.05.089 ◽

2011 ◽

Vol 164 ◽

pp. S26-S27

Author(s):

Anna Dziewulska ◽

Pawel Dobrzyn ◽

Agnieszka Dobrzyn

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Insulin Signaling ◽

Monounsaturated Fatty Acids

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The role of adipose tissue and excess of fatty acids in the induction of insulin resistance in skeletal muscle

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/17322693.1224257 ◽

2016 ◽

Vol 70 ◽

pp. 1142-1149 ◽

Cited By ~ 3

Author(s):

Agnieszka Błachnio-Zabielska ◽

Sławomir Grycel ◽

Marta Chacińska ◽

Piotr Zabielski

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acids ◽

Adipose Tissue

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Skeletal Muscle Lipid Metabolism in Exercise and Insulin Resistance

Physiological Reviews ◽

10.1152/physrev.00023.2004 ◽

2006 ◽

Vol 86 (1) ◽

pp. 205-243 ◽

Cited By ~ 294

Author(s):

Bente Kiens

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acids ◽

Molecular Mechanisms ◽

Lipid Binding ◽

Point Of View ◽

Hormone Sensitive Lipase ◽

Very Low Density Lipoproteins ◽

Skeletal Muscle Lipid

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 ∼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.

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