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This Article Full Text Full Text (PDF) All Versions of this Article: 291/1/E90    most recent 00543.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Nadeau, K. J. Articles by Draznin, B. Search for Related Content PubMed PubMed Citation Articles by Nadeau, K. J. Articles by Draznin, B.

Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle

¹Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Health Sciences Center; ²Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Health Sciences Center, Denver; ³Department of Integrative Physiology, University of Colorado, Boulder, Colorado; ⁴Geriatric Research, Education and Clinical Center, Baltimore Veterans Affairs Health Care Center; ⁵Departments of Medicine and Physiology, University of Maryland School of Medicine, Baltimore, Maryland; ⁶Departments of Internal Medicine and Pediatrics, University of South Florida, College of Medicine, Tampa, Florida; and ⁷Veterans Affairs Research Service, Denver Veterans Affairs Medical Center, Denver, Colorado

Submitted 9 November 2005 ; accepted in final form 26 January 2006

Intramuscular triglyceride (IMTG) deposition in skeletal muscle is associated with obesity and type 2 diabetes (T2DM) and is thought to be related to insulin resistance (IR). Curiously, despite enhanced skeletal muscle insulin sensitivity, highly trained athletes and calorie-restricted (CR) monkeys also have increased IMTG. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the biosynthesis of cholesterol and fatty acids. SREBP-1 is increased by insulin in skeletal muscle in vitro and in skeletal muscle of IR subjects, but SREBP-1 expression has not been examined in exercise training or calorie restriction. We examined the relationship between IMTG and SREBP-1 expression in animal models of exercise and calorie restriction. Gastrocnemius and soleus muscle biopsies were obtained from 38 Sprague-Dawley rats (18 control and 20 exercise trained). Triglyceride content was higher in the gastrocnemius and soleus muscles of the trained rats. SREBP-1c mRNA, SREBP-1 precursor and mature proteins, and fatty acid synthase (FAS) protein were increased with exercise training. Monkeys (Macaca mulatta) were CR for a mean of 10.4 years, preventing weight gain and IR. Vastus lateralis muscle was obtained from 12 monkeys (6 CR and 6 controls). SREBP-1 precursor and mature proteins and FAS protein were higher in the CR monkeys. In addition, phosphorylation of ERK1/ERK2 was increased in skeletal muscle of CR animals. In summary, SREBP-1 protein and SREBP-1c mRNA are increased in interventions that increase IMTG despite enhanced insulin sensitivity. CR and exercise-induced augmentation of SREBP-1 expression may be responsible for the increased IMTG seen in skeletal muscle of highly conditioned athletes.

muscle lipid; lipid metabolism; insulin signaling; insulin sensitivity; sterol regulatory element-binding protein-1