Benton Carley R, Han Xiao-Xia, Febbraio Maria, Graham Terry E, Bonen Arend
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
J Appl Physiol (1985). 2006 Feb;100(2):377-83. doi: 10.1152/japplphysiol.00781.2005. Epub 2005 Oct 13.
PGC-1alpha is a key regulator of tissue metabolism, including skeletal muscle. Because it has been shown that PGC-1alpha alters the capacity for lipid metabolism, it is possible that PGC-1alpha expression is regulated by the intramuscular lipid milieu. Therefore, we have examined the relationship between PGC-1alpha protein expression and the intramuscular fatty acid accumulation in hindlimb muscles of animals in which the capacity for fatty acid accumulation in muscle is increased (Zucker obese rat) or reduced [FAT/CD36 null (KO) mice]. Rates of palmitate incorporation into triacylglycerols were determined in perfused red (RG) and white gastrocnemius (WG) muscles of lean and obese Zucker rats and in perfused RG and WG muscles of FAT/CD36 KO and wild-type (WT) mice. In obese Zucker rats, the rate of palmitate incorporation into triacylglycerol depots in RG and WG muscles were 28 and 24% greater than in lean rats (P < 0.05). In FAT/CD36 KO mice, the rates of palmitate incorporation into triacylglycerol depots were lower in RG (-50%) and WG muscle (-24%) compared with the respective muscles in WT mice (P < 0.05). In the obese animals, PGC-1alpha protein content was reduced in both RG (-13%) and WG muscles (-15%) (P < 0.05). In FAT/CD36 KO mice, PGC-1alpha protein content was upregulated in both RG (+32%, P < 0.05) and WG muscles (+50%, P < 0.05). In conclusion, from studies in these two animal models, it appears that PGC-1alpha protein expression is inversely related to components of intramuscular lipid metabolism, because 1) PGC-1alpha protein expression is downregulated when triacylglycerol synthesis rates, an index of intramuscular lipid metabolism, are increased, and 2) PGC-1alpha protein expression is upregulated when triacylglycerol synthesis rates are reduced. Therefore, we speculate that the intramuscular lipid sensing may be involved in regulating the protein expression of PGC-1alpha in skeletal muscle.
PGC-1α是包括骨骼肌在内的组织代谢的关键调节因子。由于已有研究表明PGC-1α会改变脂质代谢能力，因此PGC-1α的表达可能受肌肉内脂质环境的调节。因此，我们研究了肌肉脂肪酸蓄积能力增强的动物（ Zucker肥胖大鼠）或降低的动物[FAT/CD36基因敲除（KO）小鼠]后肢肌肉中PGC-1α蛋白表达与肌肉内脂肪酸蓄积之间的关系。测定了瘦型和肥胖型Zucker大鼠灌注的红色（RG）和白色腓肠肌（WG）以及FAT/CD36基因敲除小鼠和野生型（WT）小鼠灌注的RG和WG肌肉中棕榈酸酯掺入三酰甘油的速率。在肥胖的Zucker大鼠中，RG和WG肌肉中棕榈酸酯掺入三酰甘油储存库的速率分别比瘦型大鼠高28%和24%（P<0.05）。与WT小鼠相应肌肉相比，FAT/CD36基因敲除小鼠中，RG（-50%）和WG肌肉（-24%）中棕榈酸酯掺入三酰甘油储存库的速率较低（P<0.05）。在肥胖动物中，RG（-13%）和WG肌肉（-15%）中的PGC-1α蛋白含量均降低（P<0.05）。在FAT/CD36基因敲除小鼠中，RG（+32%，P<0.05）和WG肌肉（+50%，P<0.05）中的PGC-1α蛋白含量均上调。总之，从这两种动物模型的研究来看，PGC-1α蛋白表达似乎与肌肉内脂质代谢成分呈负相关，因为1）当作为肌肉内脂质代谢指标的三酰甘油合成速率增加时，PGC-1α蛋白表达下调；2）当三酰甘油合成速率降低时，PGC-1α蛋白表达上调。因此，我们推测肌肉内脂质感应可能参与调节骨骼肌中PGC-1α的蛋白表达。
