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Nutrient-Gene Interactions

Skeletal Muscle Sterol Regulatory Element Binding Protein-1c Decreases with Food Deprivation and Increases with Feeding in Rats

Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Health Science Center, Denver, CO 80262

²To whom correspondence should be addressed. E-mail: Michael.Bizeau{at}uchsc.edu.

Sterol regulatory element binding protein-1c (SREBP-1c) is a transcription factor that responds to nutritional status and regulates metabolic gene expression in liver and adipose tissue. Although SREBP-1c RNA is expressed in skeletal muscle, little is known about its regulation in this tissue. To determine whether SREBP-1c is regulated by nutritional status in muscle, rats were food deprived for 48 h and then given access to a semipurified high cornstarch diet for 0, 6, 12 or 24 h. At each time point, blood was drawn for measurement of glucose and insulin concentrations, and the soleus, gastrocnemius and the white portion of the quadriceps muscle were removed for measurement of SREBP-1c RNA and protein. SREBP-1c RNA was increased (P < 0.05) by 6 h of refeeding and peaked at 12 h (fivefold in soleus and gastrocnemius, fourfold in white vastus) in all muscles studied. SREBP-1a RNA was not altered by refeeding. In accordance with the RNA data, the 125-kDa SREBP-1 protein increased with refeeding. To determine whether food deprivation decreased SREBP-1c RNA, rats were fed a high cornstarch diet during their normal diurnal cycle. Food was withdrawn at the beginning of the light cycle and muscles collected at 0, 6, 12 and 24 h after food was removed. SREBP-1c RNA decreased at all time points and was 60% lower in the soleus and gastrocnemius and 75% lower in the white quadriceps after 24 h. Additional refeeding experiments were conducted using a high fat diet in place of a high cornstarch diet. This diet diminished the increase in SREBP-1c RNA at all time points and in all muscles. This effect could not be explained by plasma glucose or insulin concentration. In conclusion, SREBP-1c RNA and SREBP-1 protein levels respond to nutritional status in skeletal muscle.

KEY WORDS: • skeletal muscle • transcription factor • insulin • glucose • rats

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