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Am J Physiol Regul Integr Comp Physiol 287: R218-R227, 2004. First published March 4, 2004; doi:10.1152/ajpregu.00377.2003
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APPETITE, OBESITY AND METABOLISM

In vivo regulation of SREBP-1c in skeletal muscle: effects of nutritional status, glucose, insulin, and leptin

S. Renee Commerford, Li Peng, John J. Dubé, and Robert M. O'Doherty

Department of Medicine, Division of Endocrinology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261

Submitted 9 July 2003 ; accepted in final form 16 February 2004

Sterol regulatory element binding protein-1c (SREBP-1c), a transcription factor that is important for mediating insulin effects on metabolic gene expression in liver during the fasted-to-fed transition, is also expressed in skeletal muscle. However, the regulation and role of SREBP-1c in skeletal muscle are poorly understood. The present study compared the effects of nutritional status, physiological hyperinsulinemic clamps, and adenovirus-mediated hyperleptinemia (HLEP) in rats on expression of SREBP-1c and other metabolic genes in skeletal muscle. Three- and 6-h refeeding of 18-h-fasted animals increased levels of SREBP-1c mRNA and the SREBP-1 protein (full length and mature) in gastrocnemius muscle (P < 0.05). Fatty acid synthase (FAS) and hexokinase II (HKII) mRNA levels were also increased by refeeding, and uncoupling protein 3 (UCP3) mRNA level was decreased (all P < 0.05). Surprisingly, 3-h hyperinsulinemic clamps did not increase gastrocnemius muscle SREBP-1c and FAS mRNA levels or SREBP-1 protein levels but did increase HKII mRNA levels and decrease UCP3 mRNA levels (P < 0.05). HLEP reduced refeeding-induced increases of SREBP-1c and FAS mRNA levels but did not reduce the level of SREBP-1 protein. We conclude that 1) skeletal muscle SREBP-1c gene expression is regulated by nutritional status in a fashion similar to that observed in liver and adipose tissue, 2) physiological hyperinsulinemia is not sufficient to imitate the effects of refeeding on SREBP-1c gene expression, and 3) leptin suppresses refeeding effects on SREBP-1c mRNA levels.

nutrient partitioning; lipids; gene expression



Address for reprint requests and other correspondence: R. M. O'Doherty, 200 Lothrop St., BST-E1140, Pittsburgh, PA 15261 (Odohertyr{at}msx.dept-med.pitt.edu).




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