Watt Matthew J, Holmes Anna G, Steinberg Gregory R, Mesa Jose L, Kemp Bruce E, Febbraio Mark A
Skeletal Muscle Research Laboratory, School of Medical Sciences, RMIT Univ., PO Box 71, Bundoora 3083, Victoria, Australia.
Am J Physiol Endocrinol Metab. 2004 Jul;287(1):E120-7. doi: 10.1152/ajpendo.00542.2003. Epub 2004 Jan 28.
Intramuscular triacylglycerols (IMTG) are proposed to be an important metabolic substrate for contracting muscle, although this remains controversial. To test the hypothesis that reduced plasma free fatty acid (FFA) availability would increase IMTG degradation during exercise, seven active men cycled for 180 min at 60% peak pulmonary O(2) uptake either without (CON) or with (NA) prior ingestion of nicotinic acid to suppress adipose tissue lipolysis. Skeletal muscle and adipose tissue biopsy samples were obtained before and at 90 and 180 min of exercise. NA ingestion decreased (P < 0.05) plasma FFA at rest and completely suppressed the exercise-induced increase in plasma FFA (180 min: CON, 1.42 +/- 0.07; NA, 0.10 +/- 0.01 mM). The decreased plasma FFA during NA was associated with decreased (P < 0.05) adipose tissue hormone-sensitive lipase (HSL) activity (CON: 13.9 +/- 2.5, NA: 9.1 +/- 3.0 nmol.min(-1).mg protein(-1)). NA ingestion resulted in decreased whole body fat oxidation and increased carbohydrate oxidation. Despite the decreased whole body fat oxidation, net IMTG degradation was greater in NA compared with CON (net change: CON, 2.3 +/- 0.8; NA, 6.3 +/- 1.2 mmol/kg dry mass). The increased IMTG degradation did not appear to be due to reduced fatty acid esterification, because glycerol 3-phosphate activity was not different between trials and was unaffected by exercise (rest: 0.21 +/- 0.07; 180 min: 0.17 +/- 0.04 nmol.min(-1).mg protein(-1)). HSL activity was not increased from resting rates during exercise in either trial despite elevated plasma epinephrine, decreased plasma insulin, and increased ERK1/2 phosphorylation. AMP-activated protein kinase (AMPK)alpha1 activity was not affected by exercise or NA, whereas AMPKalpha2 activity was increased (P < 0.05) from rest during exercise in NA and was greater (P < 0.05) than in CON at 180 min. These data suggest that plasma FFA availability is an important mediator of net IMTG degradation, and in the absence of plasma FFA, IMTG degradation cannot maintain total fat oxidation. These changes in IMTG degradation appear to disassociate, however, from the activity of the key enzymes responsible for synthesis and degradation of this substrate.
肌内三酰甘油（IMTG）被认为是收缩肌肉的一种重要代谢底物，尽管这一点仍存在争议。为了验证降低血浆游离脂肪酸（FFA）可用性会增加运动期间IMTG降解的假设，七名活跃男性以60%的峰值肺氧摄取量进行180分钟的骑行，一组在骑行前未服用（CON组）烟碱酸，另一组（NA组）在骑行前服用烟碱酸以抑制脂肪组织脂解。在运动前、运动90分钟和180分钟时采集骨骼肌和脂肪组织活检样本。服用烟碱酸降低了（P<0.05）静息时的血浆FFA，并完全抑制了运动诱导的血浆FFA升高（180分钟时：CON组，1.42±0.07；NA组，0.10±0.01 mM）。NA组运动期间血浆FFA降低与脂肪组织激素敏感性脂肪酶（HSL）活性降低（P<0.05）相关（CON组：13.9±2.5，NA组：9.1±3.0 nmol·min⁻¹·mg蛋白质⁻¹）。服用烟碱酸导致全身脂肪氧化减少和碳水化合物氧化增加。尽管全身脂肪氧化减少，但与CON组相比，NA组的IMTG净降解更大（净变化：CON组，2.3±0.8；NA组，6.3±1.2 mmol/kg干质量）。IMTG降解增加似乎不是由于脂肪酸酯化减少，因为甘油3-磷酸活性在各试验之间没有差异，且不受运动影响（静息时：0.21±0.07；180分钟时：0.17±0.04 nmol·min⁻¹·mg蛋白质⁻¹）。在任何一个试验中，尽管血浆肾上腺素升高、血浆胰岛素降低和ERK1/2磷酸化增加，但运动期间HSL活性均未高于静息水平。AMP激活的蛋白激酶（AMPK）α1活性不受运动或烟碱酸的影响，而AMPKα2活性在NA组运动期间较静息时增加（P<0.05），且在180分钟时高于CON组（P<0.05）。这些数据表明，血浆FFA可用性是IMTG净降解的重要调节因子，并且在没有血浆FFA的情况下，IMTG降解无法维持总脂肪氧化。然而，IMTG降解的这些变化似乎与负责该底物合成和降解的关键酶的活性无关。
