Jakus Peter B, Sandor Attila, Janaky Tamas, Farkas Viktoria
Medical Faculty, Department of Biochemistry and Medical Chemistry, University of Pecs, H-7624 Pecs, Hungary.
J Lipid Res. 2008 Feb;49(2):332-9. doi: 10.1194/jlr.M700316-JLR200. Epub 2007 Nov 5.
Rats were exposed to cold and then reacclimated at neutral temperature. Changes related to fatty acid and glucose metabolism in brown and white adipose tissues (BAT and WAT) and in muscle were then examined. Of the many proteins involved in the metabolic response, two lipogenic enzymes, acetyl-coenzyme A carboxylase (ACC) and ATP-citrate lyase, were found to play a pervasive role and studied in detail. Expression of the total and phosphorylated forms of both lipogenic enzymes in response to cold increased in BAT but decreased in WAT. Importantly, in BAT, only the phosphorylation of the ACC1 isoenzyme was enhanced, whereas that of ACC2 remained unchanged. The activities of these enzymes and the in vivo rate of FFA synthesis together suggested that WAT supplies BAT with FFA and glucose by decreasing its own synthetic activity. Furthermore, cold increased the glucose uptake of BAT by stimulating the expression of components of the insulin signaling cascade, as observed by the enhanced expression and phosphorylation of Akt and GSK-3. In muscle, these changes were observed only during reacclimation, when serum insulin also increased. Such changes may be responsible for the extreme glycogen accumulation in the BAT of rats reacclimated from cold.
将大鼠暴露于寒冷环境,然后在中性温度下重新适应。随后检测了棕色和白色脂肪组织(BAT和WAT)以及肌肉中与脂肪酸和葡萄糖代谢相关的变化。在参与代谢反应的众多蛋白质中,发现两种生脂酶,即乙酰辅酶A羧化酶(ACC)和ATP-柠檬酸裂解酶发挥着普遍作用,并对其进行了详细研究。两种生脂酶的总形式和磷酸化形式在BAT中对寒冷的反应中表达增加,而在WAT中则降低。重要的是,在BAT中,只有ACC1同工酶的磷酸化增强,而ACC2的磷酸化保持不变。这些酶的活性以及体内游离脂肪酸(FFA)合成速率共同表明,WAT通过降低自身的合成活性为BAT提供FFA和葡萄糖。此外,如通过Akt和GSK-3的表达增强和磷酸化所观察到的,寒冷通过刺激胰岛素信号级联反应成分的表达增加了BAT对葡萄糖的摄取。在肌肉中,这些变化仅在重新适应期间观察到,此时血清胰岛素也增加。这些变化可能是导致从寒冷环境重新适应的大鼠BAT中糖原极度积累的原因。