Increasing muscle carnitine content alters muscle fuel metabolism and improves exercise performance in humans

摘要

Insulin increases muscle total carnitine (TC) content during acute i. v. L-carnitine infusion (Stephens et al., 2006). Here we determined the effects of chronic ingestion of L-carnitine and carbohydrate (CHO) on muscle TC content and exercise metabolism and performance. On 2 occasions,14 healthy, moderately trained, male volunteers (age 25.9 (+-) 2.1yr， BMI 23.0 (+-) 0.8 kg/m ) performed an exercise test comprising 30 min cycling at 50% and 80% VO_2max, followed by a 30 min performance trial. Muscle biopsies were obtained at rest and after exercise at 50% and 80% VO_2max on each occasion. Following the first exercise visit volunteers ingested either 80 g of CHO (Control) or 2 g of L-carnitine L-tartrate (containing 1.32 g of L-carnitine) and 80 g of CHO (Carnitine) twice per day for 24 wk in a randomised, double blind manner. Muscle TC increased by 20% in Carnitine (22 (+-) 1.1to 26.7 (+-) 2.4，< 0.05)， whilst it was unchanged in Control At 50% VO_2max, the Carnitine group exhibited 55% less muscle glycogen utilisation ((DELTA) 26.9 (+-) 4.4 vs 60.3 (+-) 9.4 mmol-kg_1dry muscle (dm), P<0.05) and 30%less activation of the pyruvate dehydrogenase complex (PDC， (DELTA) 0.5 (+-) 0.1 vs 0.7 (+-) 0.1mmol acetyl Co А/min kg~(-1) wet muscle (wm), P< 0.05) compared to Control Conversely, at 80% V02max, muscle PDC activation status was 45% higher (2.3 (+-) 0.2 vs 1.6(+-) 0.1mmol acetyl CoA/min kg~(-1)wm,P<0.05)， acetylcarmtme content was 16% greater (18.4 (+-)1.7 vs 15,8 (+-) 1.4 mmol.kg~(-1)dm,P<0.10) and muscle lactate content was 44% lower (25.0 (+-) 4.1 vs 44.4 +- 6.9 mmol kg~（-1）dm, P < 0.05) in Carnitine compared to Control. The Carnitine group also demonstrated a 10% increase in output from baseline in the performance trial (343 (+-) 20 vs 310 (+-) 26 kJ， P < 0.01)， whilst work output was unchanged in Control. Here we show for the first time that combined CHO and L-carnitine ingestion increased muscle TC content Furthermore, increasing muscle TC dampened muscle PDC activation and CHO utilisation during low-intensity exercise, and lowered muscle lactate accumulation by increasing PDC activation status and flux during higher intensity exercise. These events were associated with improved exercise performance. Here we demonstrate a dual role of carnitine in muscle energy metabolism that is exercise intensity dependent. Thus, increasing muscle TC spares muscle glycogen during lower intensity exercise, possibly by increasing fat oxidation, but during higher intensity exercise results in a better matching of glycolytic and PDC flux, thereby lowering muscle lactate accumulation.