Chien D, Dean D, Saha A K, Flatt J P, Ruderman N B
Diabetes Unit, Section of Endocrinology and Departments of Medicine and Physiology, Boston Medical Center, Boston, Massachusetts 02118, USA.
Am J Physiol Endocrinol Metab. 2000 Aug;279(2):E259-65. doi: 10.1152/ajpendo.2000.279.2.E259.
Malonyl-CoA acutely regulates fatty acid oxidation in liver in vivo by inhibiting carnitine palmitoyltransferase. Thus rapid increases in the concentration of malonyl-CoA, accompanied by decreases in long-chain fatty acyl carnitine (LCFA-carnitine) and fatty acid oxidation have been observed in liver of fasted-refed rats. It is less clear that it plays a similar role in skeletal muscle. To examine this question, whole body respiratory quotients (RQ) and the concentrations of malonyl-CoA and LCFA-carnitine in muscle were determined in 48-h-starved rats before and at various times after refeeding. RQ values were 0.82 at baseline and increased to 0.93, 1. 0, 1.05, and 1.09 after 1, 3, 12, and 18 h of refeeding, respectively, suggesting inhibition of fat oxidation in all tissues. The increases in RQ at each time point correlated closely (r = 0.98) with increases (50-250%) in the concentration of malonyl-CoA in soleus and gastrocnemius muscles and decreases in plasma FFA and muscle LCFA-carnitine levels. Similar changes in malonyl-CoA and LCFA-carnitine were observed in liver. The increases in malonyl-CoA in muscle during refeeding were not associated with increases in the assayable activity of acetyl-CoA carboxylase (ACC) or decreases in the activity of malonyl-CoA decarboxylase (MCD). The results suggest that, during refeeding after a fast, decreases in fatty acid oxidation occur rapidly in muscle and are attributable both to decreases in plasma FFA and increases in the concentration of malonyl-CoA. They also suggest that the increase in malonyl-CoA in this situation is not due to changes in the assayable activity of either ACC or MCD or an increase in the cytosolic concentration of citrate.
丙二酰辅酶A通过抑制肉碱棕榈酰转移酶在体内急性调节肝脏中的脂肪酸氧化。因此，在禁食-再喂养大鼠的肝脏中观察到丙二酰辅酶A浓度迅速增加，同时长链脂肪酰肉碱（LCFA-肉碱）和脂肪酸氧化减少。丙二酰辅酶A在骨骼肌中是否发挥类似作用尚不清楚。为了研究这个问题，测定了48小时饥饿大鼠在再喂养前和再喂养后不同时间的全身呼吸商（RQ）以及肌肉中丙二酰辅酶A和LCFA-肉碱的浓度。基线时RQ值为0.82，再喂养1、3、12和18小时后分别增加到0.93、1.0、1.05和1.09，表明所有组织中的脂肪氧化均受到抑制。每个时间点RQ的增加与比目鱼肌和腓肠肌中丙二酰辅酶A浓度的增加（50%-250%）以及血浆游离脂肪酸（FFA）和肌肉LCFA-肉碱水平的降低密切相关（r = 0.98）。在肝脏中也观察到丙二酰辅酶A和LCFA-肉碱的类似变化。再喂养期间肌肉中丙二酰辅酶A的增加与乙酰辅酶A羧化酶（ACC）的可检测活性增加或丙二酰辅酶A脱羧酶（MCD）的活性降低无关。结果表明，禁食后的再喂养期间，肌肉中脂肪酸氧化迅速减少，这既归因于血浆FFA的减少，也归因于丙二酰辅酶A浓度的增加。它们还表明，在这种情况下丙二酰辅酶A的增加不是由于ACC或MCD的可检测活性变化或柠檬酸胞质浓度的增加。
