Cited by 138Muscle Physiology and DisordersMuscle metabolism and nutritionNutrition and Health in Aging

Diminished anabolic signaling response to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity

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Rivas, Donato A., McDonald, Devin J., Rice, Nicholas P., Haran, Prashanth H., Dolnikowski, Gregory G., Fielding, Roger A.·2016·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

Abstract

The loss of skeletal muscle mass is observed in many pathophysiological conditions, including aging and obesity. The loss of muscle mass and function with aging is defined as sarcopenia and is characterized by a mismatch between skeletal muscle protein synthesis and breakdown. Characteristic metabolic features of both aging and obesity are increases in intramyocellular lipid (IMCL) content in muscle. IMCL accumulation may play a mechanistic role in the development of anabolic resistance and the progression of muscle atrophy in aging and obesity. In the present study, aged and high-fat fed mice were used to determine mechanisms leading to muscle loss. We hypothesized the accumulation of bioactive lipids in skeletal muscle, such as ceramide or diacylglycerols, leads to insulin resistance with aging and obesity and the inability to activate protein synthesis, contributing to skeletal muscle loss. We report a positive association between bioactive lipid accumulation and the loss of lean mass and muscle strength. Obese and aged animals had significantly higher storage of ceramide and diacylglycerol compared with young. Furthermore, there was an attenuated insulin response in components of the mTOR anabolic signaling pathway. We also observed differential increases in the expression of inflammatory cytokines and the phosphorylation of IκBα with aging and obesity. These data challenge the accepted role of increased inflammation in obesity-induced insulin resistance in skeletal muscle. Furthermore, we have now established IκBα with a novel function in aging-associated muscle loss that may be independent of its previously understood role as an NF-κB inhibitor.

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Authors
Rivas, D. A., McDonald, D. J., Rice, N. P., Haran, P. H., Dolnikowski, G. G., & Fielding, R. A.
Affiliations
Tufts University (US)
Corresponding author
Rivas, Donato A.
Venue
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Published
2016-04-01
Volume
310
Issue
7
Pages
R561-R569
ISSN
  • 0363-6119 (ISSN-L)
  • 1522-1490
OpenAlex
W2321444106
Cited by
132
References
53
Citations by year
2026: 9 · 2025: 8 · 2024: 19 · 2023: 10 · 2022: 21 · 2021: 15 · 2020: 13 · 2019: 7 · 2018: 16 · 2017: 11 · 2016: 3
FWCI
6.41
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Agriculture (USDA) (58-1950-4-003)
  • HHS | NIH | National Institute on Aging (U.S. National Institute on Aging) (1P30AG031679)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
sarcopenia, skeletal muscle atrophy, intramyocellular lipid, insulin resistance, anabolic signaling, mTOR signaling, ceramide, diacylglycerol, bioactive lipids, inflammation, IκBα phosphorylation, NF-κB, aging, obesity, muscle protein synthesis, muscle strength
MeSH terms
Aging, Animals, Insulin, Insulin Resistance, Lipids, Male, Metabolism, Mice, Inbred C57BL, Myositis, Obesity, Signal Transduction, Muscle, Skeletal, Lipid Metabolism, Mice, Sarcopenia

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