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1 Department of Medicine, Division of Endocrinology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: odohertyr{at}msx.dept-med.pitt.edu.
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 is 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. 3h and 6h refeeding of 18hr fasted animals increased levels of SREBP-1c mRNA and the SREBP-1 protein (full length and mature) in gastrocnemius muscle (GAS, 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, 3h hyperinsulinemic clamps did not increase GAS 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.
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