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J Appl Physiol (October 13, 2005). doi:10.1152/japplphysiol.00781.2005
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Submitted on July 1, 2005
Accepted on October 11, 2005

INVERSE RELATIONSHIP BETWEEN PGC-1{alpha} PROTEIN EXPRESSION AND TRIACYLGLYCEROL ACCUMULATION IN RODENT SKELETAL MUSCLE

Carley R. Benton1, Xiao-Xia Han2, Maria Febbraio3, Terry E. Graham2, and Arend Bonen2*

1 Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada
2 Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada
3 Department of Cell Biology, Lerner Research Institute, Cleveland, Ohio, USA

* To whom correspondence should be addressed. E-mail: abonen{at}uoguelph.ca.

PGC-1{alpha} is a key regulator of tissue metabolism, including skeletal muscle. Since it has been shown that PGC-1{alpha} alters the capacity for lipid metabolism, it is possible that PGC-1{alpha} expression is regulated by the intramuscular lipid milieu. Therefore, we have examined the relationship between PGC-1{alpha} 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 (obese Zucker rat) or reduced (FAT/CD36 null 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 null mice (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 null mice the rates of palmitate incorporation into triacylglycerol depots were lower in RG (-50%) and WG muscle (-24%) compared to the respective muscles in WT mice (P<0.05). In the obese animals PGC-1{alpha} protein content was reduced in both RG (-13%) and WG muscles (-15%) (P < 0.05). In FAT/CD36 null mice,PGC-1{alpha} 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-1{alpha} protein expression is inversely related to components of intramuscular lipid metabolism, as a) PGC-1{alpha} protein expression is down-regulated when triacylglycerol synthesis rates, an index of intramuscular lipid accumulation, are increased, and b) PGC-1{alpha} protein expression is up-regulated when triacylglycerol synthesis rates are reduced. Therefore, we speculate that intramuscular lipid sensing is involved in regulating the protein expression of PGC-1{alpha} .




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