Mantha L, Deshaies Y
Department of Physiology, School of Medicine, Laval University, Quebec, Quebec, Canada G1K 7P4.
Am J Physiol. 1998 Jun;274(6):R1769-76. doi: 10.1152/ajpregu.1998.274.6.R1769.
This study aimed to identify the metabolic steps involved in the acute hypotriglyceridemia brought about by increased energy expenditure (cold exposure) and to assess the causative involvement of some determinants of triglyceride (TG) metabolism as well as that of the beta-adrenergic pathway. Rats were kept at 24 degreesC or exposed to 10 degreesC for 3 h after acute administration of the beta-adrenergic antagonist propranolol (Prop) or vehicle. Cold exposure increased the rate of TG secretion (Triton WR1339 method) into the circulation by 50% (P < 0.0005), an effect that was blunted by Prop. The cold-induced increase in TG secretion was closely related to changes in circulating nonesterified fatty acid levels, but not with serum insulin concentrations. Despite an increase in TG secretion, serum TG levels after acute cold exposure fell to 50% (P < 0.002) of those measured at 24 degreesC, indicating that the lowering of serum TG was entirely due to an increase in their rate of intravascular hydrolysis. This was confirmed by observing a 70% increase (P < 0.002) in the rate of clearance of an exogenous TG emulsion in cold-exposed rats compared with those kept in the warm. Prop treatment before cold exposure decreased (approximately 30%, P < 0.005) the cold-induced stimulation of TG hydrolysis. The increased TG clearance rate in cold-exposed animals occurred in the absence of any change in the intravascular availability of lipoprotein lipase (LPL). In contrast, the activity of LPL displayed a tissue-specific response to cold exposure, being reduced by one-half in white adipose tissue (P < 0.0005) and increased in brown adipose tissue (130%, P < 0.0001) and the heart (50%, P < 0.001). These findings show that, in the postprandial state, an acute increase in energy expenditure induced by cold exposure results in a lowering of serum TG entirely due to an increase in their rate of intravascular hydrolysis and that serum TGs are lowered despite an increase in the rate of TG secretion into the circulation. More efficient TG hydrolysis occurs independently of the intravascular availability of LPL. The study further shows that the effects of cold exposure on serum TG concentration and their rates of secretion and clearance are in large part mediated by the beta-adrenergic pathway.
本研究旨在确定由能量消耗增加(冷暴露)引起的急性低甘油三酯血症所涉及的代谢步骤,并评估甘油三酯(TG)代谢的一些决定因素以及β-肾上腺素能途径的因果关系。大鼠在急性给予β-肾上腺素能拮抗剂普萘洛尔(Prop)或赋形剂后,分别置于24℃或暴露于10℃ 3小时。冷暴露使TG分泌入循环的速率(Triton WR1339法)增加了50%(P<0.0005),这一效应被Prop减弱。冷诱导的TG分泌增加与循环中非酯化脂肪酸水平的变化密切相关,但与血清胰岛素浓度无关。尽管TG分泌增加,但急性冷暴露后的血清TG水平降至24℃时测量值的50%(P<0.002),这表明血清TG的降低完全是由于其血管内水解速率增加。与置于温暖环境中的大鼠相比,冷暴露大鼠中外源性TG乳剂清除率增加70%(P<0.002),证实了这一点。冷暴露前的Prop处理降低了(约30%,P<0.005)冷诱导的TG水解刺激。冷暴露动物中TG清除率的增加发生在脂蛋白脂肪酶(LPL)血管内可用性无任何变化的情况下。相反,LPL的活性对冷暴露表现出组织特异性反应,在白色脂肪组织中降低了一半(P<0.0005),在棕色脂肪组织中增加(130%,P<0.0001),在心脏中增加(50%,P<0.001)。这些发现表明,在餐后状态下,冷暴露引起的能量消耗急性增加导致血清TG降低完全是由于其血管内水解速率增加,并且尽管TG分泌入循环的速率增加,但血清TG仍降低。更有效的TG水解独立于LPL的血管内可用性而发生。该研究进一步表明,冷暴露对血清TG浓度及其分泌和清除速率的影响在很大程度上由β-肾上腺素能途径介导。