Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle
Abstract
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.
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The effects of caloric restriction on intramyocellular lipids are mixed, with studies reporting increases, decreases and no change.
“the effects of CR have been shown to be mixed, with studies reporting increases, decreases and no change [124–127].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [127]
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- Authors
- Nadeau, K. J., Ehlers, L. B., Aguirre, L. E., Moore, R. L., Jew, K. N., Ortmeyer, H. K., Hansen, B. C., Reusch, J. E. B., & Draznin, B.
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2006-07
- Volume
- 291
- Issue
- 1
- Pages
- E90-E98
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2130101437
- Cited by
- 57
- References
- 76
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 2 · 2013: 4 · 2012: 3
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (R01-DIC06741, P0156481)
- National Heart, Lung, and Blood Institute (R01-HL-72790, R01HL072790)
- National Institute of Diabetes and Digestive and Kidney Diseases (5-P30-DK-48520-10, P30DK048520)
- National Center for Research Resources (K23RR020038)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- SREBP1, intramuscular triglycerides, skeletal muscle, exercise training, caloric restriction, fatty acid synthase, insulin resistance, ERK1/2 phosphorylation, SREBP-1c, type 2 diabetes, obesity, athletes, muscle lipid metabolism
- MeSH terms
- Animals, Female, Food Deprivation, Macaca mulatta, Male, Physical Conditioning, Animal, RNA, Messenger, Triglycerides, Blotting, Western, Rats, Sprague-Dawley, Muscle, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, Rats, Sterol Regulatory Element Binding Protein 1, Fatty Acid Synthases
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