Inverse relationship between PGC-1α protein expression and triacylglycerol accumulation in rodent skeletal muscle

Abstract

PGC-1α is a key regulator of tissue metabolism, including skeletal muscle. Because it has been shown that PGC-1α alters the capacity for lipid metabolism, it is possible that PGC-1α expression is regulated by the intramuscular lipid milieu. Therefore, we have examined the relationship between PGC-1α 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-1α protein content was reduced in both RG (−13%) and WG muscles (−15%) ( P < 0.05). In FAT/CD36 KO mice, PGC-1α 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-1α protein expression is inversely related to components of intramuscular lipid metabolism, because 1) PGC-1α protein expression is downregulated when triacylglycerol synthesis rates, an index of intramuscular lipid metabolism, are increased, and 2) PGC-1α 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-1α in skeletal muscle.