Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle.
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.
Nadeau
Kristen J
KJ
The Children's Hospital, Dept. of Pediatric Endocrinology, Box 265, 1056 East 19th Ave, Denver, CO 80218, USA. nadeaukj@hotmail.com
Ehlers
Lindsay B
LB
Aguirre
Lina E
LE
Moore
Russell L
RL
Jew
Korinne N
KN
Ortmeyer
Heidi K
HK
Hansen
Barbara C
BC
Reusch
Jane E B
JE
Draznin
Boris
B
D000818:Animals; D015153:Blotting, Western; D064429:Fatty Acid Synthases / Q000378:metabolism; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism*
D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D064429:Fatty Acid Synthases