Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise

Abstract

. Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise.

Carnitine and Fat Oxidation

“…Thus, van Loon et al [2] demonstrated that a 35% decrease in the rate of fat oxidation that occurred at 72% VO 2 max, was paralleled by a 65% decline in skeletal muscle free carnitine content. Furthermore, the 2.5-fold decrease in the rate of fat oxidation during exercise at 65% VO 2 max compared to control in the afore mentioned study of Roepstorff et al [17] coincided with a 50% reduction in free carnitine availability.…”

“…Malonyl-CoA is a potent inhibitor of CPT1 activity in vitro and is a likely candidate as the intracellular regulator of the rate of long-chain fatty acid oxidation in human skeletal muscle, particularly as changes in muscle malonyl-CoA content have occurred with opposite changes in fat oxidation at rest [16]. However, despite a 122% increase in fat oxidation rates (due to depleted pre-exercise muscle glycogen content) during exercise at 65% VO 2 peak, there were no differences in muscle malonyl-CoA content compared to control [17], suggesting that malonyl-CoA does not regulate CPT1 activity during exercise. Interestingly, a reduction in intracellular pH (from 7.1 to 6.8) in vitro reduces CPT1 activity by 34-40%, independent of any physiological change in malonyl-CoA concentration [18].…”

“…Open circles are a review of results taken from [17,19,20,21,22,24] under standard conditions. Closed circles are results from [17,24] after the muscle free carnitine pool has been manipulated by 6 months of L-carnitine and carbohydrate feeding [24] or at 65% VO 2 max by reducing glycolytic flux [17] -these interventions shift the rate of fat oxidation curve up, rather than to the right. Below: Schematic diagram of the dual metabolic role of free carnitine within skeletal muscle fat (red arrows) and carbohydrate (blue arrows) oxidation.…”

Role of Adiponectin in Development and Progression of Diabetic Complications

“…Moreover, activation of AMPK has been shown to be necessary for adiponectin effects on fatty acid oxidation in skeletal muscle cells [49, 50, and 55] . AMPK activation triggers many metabolic changes that act to restore energy balance in muscle cells, such as increased glucose uptake and metabolism,and increased oxidation of fatty acids [56] . Regulation of fatty acid oxidation pathway by AMPK involves phosphorylation of acetyl-CoA carboxylase (ACC),which leads to the inhibition of ACC activity followed by a decrease in malonyl-CoA levels [56] .…”

“…AMPK activation triggers many metabolic changes that act to restore energy balance in muscle cells, such as increased glucose uptake and metabolism,and increased oxidation of fatty acids [56] . Regulation of fatty acid oxidation pathway by AMPK involves phosphorylation of acetyl-CoA carboxylase (ACC),which leads to the inhibition of ACC activity followed by a decrease in malonyl-CoA levels [56] . Adiponectin-dependent AMPK activation in skeletal musclewas associated with an increase in ACC phosphorylation and a decrease in the concentration of malonyl-CoA [52,50] .…”