TY - JOUR
T1 - Molecular regulation of fatty acid oxidation in skeletal muscle during aerobic exercise
AU - Lundsgaard, Annemarie
AU - Fritzen, Andreas Mæchel
AU - Kiens, Bente
N1 - CURIS 2018 NEXS 010
PY - 2018/1
Y1 - 2018/1
N2 - This review summarizes how fatty acid (FA) oxidation is regulated in skeletal muscle during exercise. From the available evidence it seems that acetyl-CoA availability in the mitochondrial matrix adjusts FA oxidation to exercise intensity and duration. This is executed at the step of mitochondrial fatty acyl import, as the extent of acetyl group sequestration by carnitine determines the availability of carnitine for the carnitine palmitoyltransferase 1 (CPT1) reaction. The rate of glycolysis seems therefore to be central to the amount of β-oxidation-derived acetyl-CoA that is oxidized in the tricarboxylic acid (TCA) cycle. FA oxidation during exercise is also determined by FA availability to mitochondria, dependent on trans-sarcolemmal FA uptake via cluster of differentiation 36/SR-B2 (CD36) and FAs mobilized from myocellular lipid droplets. The regulation of fatty acid (FA) oxidation during exercise is subject to multisite control allowing flexible regulation of metabolism. FA uptake is facilitated via cluster of differentiation 36/SR-B2 (CD36), which translocates to the sarcolemma at the onset of muscle contractions, thereby increasing intracellular FA availability. Carnitine availability plays an essential role in the regulation of FA oxidation. Sequestering of acetyl-CoA to carnitine by carnitine acetyltransferase (CAT) alters the free carnitine content in muscle thereby influencing the carnitine palmitoyltransferase 1 (CPT1) reaction and in turn mitochondrial FA import and oxidation. This scenario may explain the lower FA oxidation at higher exercise intensities where a high glycolytic rate leads to acetyl-CoA excess, whereas the potential for FA import into the tricarboxylic acid cycle is enhanced when the glycolytic rate is low, as during prolonged low-intensity exercise.
AB - This review summarizes how fatty acid (FA) oxidation is regulated in skeletal muscle during exercise. From the available evidence it seems that acetyl-CoA availability in the mitochondrial matrix adjusts FA oxidation to exercise intensity and duration. This is executed at the step of mitochondrial fatty acyl import, as the extent of acetyl group sequestration by carnitine determines the availability of carnitine for the carnitine palmitoyltransferase 1 (CPT1) reaction. The rate of glycolysis seems therefore to be central to the amount of β-oxidation-derived acetyl-CoA that is oxidized in the tricarboxylic acid (TCA) cycle. FA oxidation during exercise is also determined by FA availability to mitochondria, dependent on trans-sarcolemmal FA uptake via cluster of differentiation 36/SR-B2 (CD36) and FAs mobilized from myocellular lipid droplets. The regulation of fatty acid (FA) oxidation during exercise is subject to multisite control allowing flexible regulation of metabolism. FA uptake is facilitated via cluster of differentiation 36/SR-B2 (CD36), which translocates to the sarcolemma at the onset of muscle contractions, thereby increasing intracellular FA availability. Carnitine availability plays an essential role in the regulation of FA oxidation. Sequestering of acetyl-CoA to carnitine by carnitine acetyltransferase (CAT) alters the free carnitine content in muscle thereby influencing the carnitine palmitoyltransferase 1 (CPT1) reaction and in turn mitochondrial FA import and oxidation. This scenario may explain the lower FA oxidation at higher exercise intensities where a high glycolytic rate leads to acetyl-CoA excess, whereas the potential for FA import into the tricarboxylic acid cycle is enhanced when the glycolytic rate is low, as during prolonged low-intensity exercise.
KW - Glycolysis
KW - Pyruvate dehydrogenase
KW - Acetyl-CoA
KW - Carnitine palmitoyltransferase 1
KW - Carnitine acyltransferase
U2 - 10.1016/j.tem.2017.10.011
DO - 10.1016/j.tem.2017.10.011
M3 - Review
C2 - 29221849
SN - 1043-2760
VL - 29
SP - 18
EP - 30
JO - Trends in Endocrinology and Metabolism
JF - Trends in Endocrinology and Metabolism
IS - 1
ER -