Comprehensive Physiology Wiley Online Library

Lipid Metabolism in Muscle

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Supply and Cellular Uptake of Upids in Skeletal Muscles
1.1 Albumin‐Bound Fatty Acids
1.2 Fatty Acids in Circulating Lipoproteins
1.3 Skeletal Muscle Fatty Acid Uptake
2 Fatty Acid Metabolism in the Skeletal Muscle Cell
2.1 Activation and Oxidation of Fatty Acids
2.2 Intramuscular Triacylglycerols
3 Supply and Utilization of Upids During Exercise
3.1 Albumin‐Bound Fatty Acids in Plasma during Exercise
3.2 Circulating Lipoprotein‐Triacylglycerols as a Potential Source of Fatty Acids during Exercise
3.3 Contribution of Intramuscular Triacylglycerols to Fatty Acid Oxidation during Exercise
3.4 Relative Contribution of Various Sources of Lipids to Overall Fatty Acid Utilization during Exercise
3.5 Gender Differences in Lipid Utilization during Exercise
4 Effect of Training on Skeletal Muscle Lipid Utilization
4.1 Advantages of Enhanced Lipid Utilization by Trained Muscles during Exercise
4.2 Possible Causes of Increased Lipid Consumption by Trained Muscles during Exercise
4.3 Utilization of Plasma‐Borne Fatty Acids by Trained Muscles
4.4 Circulating Lipoproteins as an Additional Source of Lipids for Trained Muscles
4.5 Utilization of Intramuscular Triacylglycerols in Endurance‐Trained Muscles
4.6 Regulation of Fatty Acid Release from Intramuscular Triacylglycerols in Trained Muscles
5 Effect of Diet on Muscle Lipid Metabolism
5.1 High‐Carbohydrate vs. High‐Fat Diets in Relation to Physical Performance
5.2 Shift from Carbohydrate to Lipid Utilization by High‐Fat Diet
5.3 Source of Lipid for Muscles during High‐Fat Diet Feeding
5.4 Possible Mechanisms Underlying Increased Muscular Lipid Utilization during High‐Fat Feeding
6 Interrelationship Between Muscular Carbohydrate and Lipid Metabolism
6.1 The Glucose–Fatty Acid, or Randle, Cycle
6.2 The Existence of the Randle Cycle in Skeletal Muscle
6.3 Possible Mechanisms Underlying the Glucose‐Fatty Acid Cycle in Skeletal Muscle
6.4 A Role for Malonyl CoA in Fuel Selection in Skeletal Muscle Cells
7 Defects in the Skeletal Muscle Fatty Acid Oxidative Pathway
8 Concluding Remarks
Figure 1. Figure 1.

Schematic representation of fatty acid uptake by skeletal muscle cells. TG, triacylglycerols (very‐low‐density lipoprotein and chylomicrons); LPL, lipoprotein lipase; FA, fatty acids; Alb, albumin; ABP, albumin‐binding protein; FAT, fatty acid–transporter; FABP, fatty acid–binding protein; ?, route or mechanism of uptake incompletely understood.

Figure 2. Figure 2.

Mitochondrial activation, transport and oxidation of fatty acids. FABP, fatty acid–binding protein; FA, fatty acyl moieties; CoA, coenzyme A; ATP, adenosine triphosphate; AMP, adenosine monophosphate; R.C., respiratory chain; O, oxygen; fp, flavoprotein; K.C., Krebs cycle; GTP, guanosine triphosphate; GDP, guanosine diphosphate; numbers in brackets, number of ADP converted to ATP; 1, fatty acyl CoA synthetase; 2, carnitine acyl transferase I; 3, carnitine‐acyl carnitine translocase; 4, carnitine acyl transferase II; 5, fatty acyl CoA dehydrogenase; 6, enoyl CoA hydratase; 7, 3‐hydroxyacyl CoA dehydrogenase; 8, 3‐ketothiolase.

Figure 3. Figure 3.

Triacylglycerol–fatty acid cycle in skeletal muscle cells. FA, fatty acyl moieties; CoA, coenzyme A; Pi, inorganic phosphate; 1, glycerol 3‐phosphate dehydrogenase; 2, glycerol 3‐phosphate acyltransferase; 3, 1‐acylglycerol‐3‐phosphate acyl‐transferase; 4, phosphatidic acid phosphatase; 5, diacylglycerol acyltransferase; 6, triacylglycerol lipase; 7, diacylglycerol lipase; 8, monoacylglycerol lipase; 9, glycerol kinase; ?, indicates most likely insignificant in skeletal muscle.

Figure 4. Figure 4.

Putative hormonal regulation of skeletal muscle lipase 201. Raised intracellular cAMP levels by hormone (H) is assumed to activate hormone‐sensitive neutral triacylglycerol lipase (HSL). Triacylglycerol is hydrolyzed and fatty acids are utilized for oxidative energy conversion (β‐oxidation). cAMP is also thought to activate the synthesis and transport of lipoprotein lipase (LPL) to the luminal surface of the endothelium, making more fatty acids available from circulatory triacylglycerols (TG) for replenishment of the depleted intramuscular triacylglycerol pool after exercise.

Figure 5. Figure 5.

Schematic description of the glucose–fatty acid cycle and malonyl CoA inhibition of fatty acid oxidation. Solid and broken lines/arrows refer to metabolic conversions and modes of action, respectively. ⊖ and ⊕ refer to inhibition and stimulation, respectively. 1, citrate synthase; 2, ATP, citrate lyase; 3, acetyl CoA carboxylase; 4, carnitine acyltransferase I; 5, phosphofructokinase; 6, pyruvate dehydrogenase; 7, hexokinase.



Figure 1.

Schematic representation of fatty acid uptake by skeletal muscle cells. TG, triacylglycerols (very‐low‐density lipoprotein and chylomicrons); LPL, lipoprotein lipase; FA, fatty acids; Alb, albumin; ABP, albumin‐binding protein; FAT, fatty acid–transporter; FABP, fatty acid–binding protein; ?, route or mechanism of uptake incompletely understood.



Figure 2.

Mitochondrial activation, transport and oxidation of fatty acids. FABP, fatty acid–binding protein; FA, fatty acyl moieties; CoA, coenzyme A; ATP, adenosine triphosphate; AMP, adenosine monophosphate; R.C., respiratory chain; O, oxygen; fp, flavoprotein; K.C., Krebs cycle; GTP, guanosine triphosphate; GDP, guanosine diphosphate; numbers in brackets, number of ADP converted to ATP; 1, fatty acyl CoA synthetase; 2, carnitine acyl transferase I; 3, carnitine‐acyl carnitine translocase; 4, carnitine acyl transferase II; 5, fatty acyl CoA dehydrogenase; 6, enoyl CoA hydratase; 7, 3‐hydroxyacyl CoA dehydrogenase; 8, 3‐ketothiolase.



Figure 3.

Triacylglycerol–fatty acid cycle in skeletal muscle cells. FA, fatty acyl moieties; CoA, coenzyme A; Pi, inorganic phosphate; 1, glycerol 3‐phosphate dehydrogenase; 2, glycerol 3‐phosphate acyltransferase; 3, 1‐acylglycerol‐3‐phosphate acyl‐transferase; 4, phosphatidic acid phosphatase; 5, diacylglycerol acyltransferase; 6, triacylglycerol lipase; 7, diacylglycerol lipase; 8, monoacylglycerol lipase; 9, glycerol kinase; ?, indicates most likely insignificant in skeletal muscle.



Figure 4.

Putative hormonal regulation of skeletal muscle lipase 201. Raised intracellular cAMP levels by hormone (H) is assumed to activate hormone‐sensitive neutral triacylglycerol lipase (HSL). Triacylglycerol is hydrolyzed and fatty acids are utilized for oxidative energy conversion (β‐oxidation). cAMP is also thought to activate the synthesis and transport of lipoprotein lipase (LPL) to the luminal surface of the endothelium, making more fatty acids available from circulatory triacylglycerols (TG) for replenishment of the depleted intramuscular triacylglycerol pool after exercise.



Figure 5.

Schematic description of the glucose–fatty acid cycle and malonyl CoA inhibition of fatty acid oxidation. Solid and broken lines/arrows refer to metabolic conversions and modes of action, respectively. ⊖ and ⊕ refer to inhibition and stimulation, respectively. 1, citrate synthase; 2, ATP, citrate lyase; 3, acetyl CoA carboxylase; 4, carnitine acyltransferase I; 5, phosphofructokinase; 6, pyruvate dehydrogenase; 7, hexokinase.

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Ger J. Van Der Vusse, Robert S. Reneman. Lipid Metabolism in Muscle. Compr Physiol 2011, Supplement 29: Handbook of Physiology, Exercise: Regulation and Integration of Multiple Systems: 952-994. First published in print 1996. doi: 10.1002/cphy.cp120121