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

• Published in: American journal of physiology: endocrinology and metabolism Vol. 291; no. 1; pp. E90 - E98
• Main Authors: Nadeau, Kristen J, Ehlers, Lindsay B, Aguirre, Lina E, Moore, Russell L, Jew, Korinne N, Ortmeyer, Heidi K, Hansen, Barbara C, Reusch, Jane E. B, Draznin, Boris
• Format: Journal Article
• Language: English
• Published: United States 01.07.2006
• Subjects: Animals; Blotting, Western; Fatty Acid Synthases - metabolism; Female; Food Deprivation - physiology; Macaca mulatta; Male; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Physical Conditioning, Animal - physiology; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Sterol Regulatory Element Binding Protein 1 - biosynthesis; Sterol Regulatory Element Binding Protein 1 - genetics; Triglycerides - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00543.2005

1 Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Health Sciences Center; 2 Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Health Sciences Center, Denver; 3 Department of Integrative Physiology, University of Colorado, Boulder, Colorado; 4 Geriatric Research, Education and Clinical Center, Baltimore Veterans Affairs Health Care Center; 5 Departments of Medicine and Physiology, University of Maryland School of Medicine, Baltimore, Maryland; 6 Departments of Internal Medicine and Pediatrics, University of South Florida, College of Medicine, Tampa, Florida; and 7 Veterans 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 Address for reprint requests and other correspondence: K. Nadeau, The Children's Hospital, Dept. of Pediatric Endocrinology, Box 265, 1056 East 19th Ave, Denver, CO 80218. (email: nadeaukj{at}hotmail.com )