Caloric Restriction Normalizes Obesity-Induced Alterations on Regulators of Skeletal Muscle Growth Signaling.
The objective of this study was to establish the impact of caloric restriction on high fat diet-induced alterations on regulators of skeletal muscle growth. We hypothesized that caloric restriction would reverse the negative effects of high fat diet-induced obesity on REDD1 and mTOR-related signaling. Following an initial 8 week period of HF diet-induced obesity, caloric restriction (CR ~30 %) was employed while mice continued to consume either a low (LF) or high fat (HF) diet for 8 weeks. Western analysis of skeletal muscle showed that CR reduced (p < 0.05) the obesity-related effects on the lipogenic protein, SREBP1. Likewise, CR reduced (p < 0.05) the obesity-related effects on the hyperactivation of mTORC1 and ERK1/2 signaling to levels comparable to the LF mice. CR also reduced (p < 0.05) obesity-induced expression of negative regulators of growth, REDD1 and cleaved caspase 3. These findings have implications for on the reversibility of dysregulated growth signaling in obese skeletal muscle, using short-term caloric restriction.
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, SUNY, 2 Sherman Hall (Office)/5 Sherman Hall, Buffalo, NY, 14214, USA.
Cory M
CM
Dungan
Department of Pharmacology and Toxicology, School of Medicine, University at Buffalo, Buffalo, NY, USA.
Ji
J
Li
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, SUNY, 2 Sherman Hall (Office)/5 Sherman Hall, Buffalo, NY, 14214, USA. davidwil@buffalo.edu.|Kinesiology Program, School of Behavioral Sciences and Education, Penn State Harrisburg, Middletown, PA, USA. davidwil@buffalo.edu.
David L
DL
Williamson
D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D059305:Diet, High-Fat / Q000009:adverse effects; D008297:Male; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
C469992:Ddit4 protein, mouse; D014157:Transcription Factors; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
Apoptosis; SREBP1; mTORC1