Abstract
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.
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Abbreviations
- CR:
-
Caloric restriction
- ERK:
-
Extracellular signal-regulated kinase
- HF:
-
High fat
- LF:
-
Low fat
- MEK:
-
MAPK/ERK kinase
- mTOR:
-
Mammalian target of rapamycin
- mTORC1:
-
mTOR complex 1
- REDD1:
-
Regulated in development and DNA damage responses 1
- rpS6:
-
Ribosomal protein S6, S6K1 p70 ribosomal protein S6 kinase-1
- SREBP1c:
-
Sterol regulatory element-binding protein 1c
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Acknowledgments
The authors would like to thank Mingxia Cui for excellent support throughout the project.
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Dungan, C.M., Li, J. & Williamson, D.L. Caloric Restriction Normalizes Obesity-Induced Alterations on Regulators of Skeletal Muscle Growth Signaling. Lipids 51, 905–912 (2016). https://doi.org/10.1007/s11745-016-4168-3
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DOI: https://doi.org/10.1007/s11745-016-4168-3