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

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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

DOI 10.1152/ajpregu.00198.2015PMC PMC4867383

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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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Additional file 1 of Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice
Morgan, H. L., Eid, N. S., Holmes, N., Henson, S., Wright, V., Coveney, C., Winder, C. L., O’Neil, D. M., Dunn, W. B., Boocock, D. J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.27022750
Additional file 10 of Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice
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Additional file 2 of Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice
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Additional file 8 of Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice
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Additional file 9 of Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice
Morgan, H. L., Eid, N. S., Holmes, N., Henson, S., Wright, V., Coveney, C., Winder, C. L., O’Neil, D. M., Dunn, W. B., Boocock, D. J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.27022777
Additional file 6 of Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice
Morgan, H. L., Eid, N. S., Holmes, N., Henson, S., Wright, V., Coveney, C., Winder, C. L., O’Neil, D. M., Dunn, W. B., Boocock, D. J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.27022768
Additional file 7 of Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice
Morgan, H. L., Eid, N. S., Holmes, N., Henson, S., Wright, V., Coveney, C., Winder, C. L., O’Neil, D. M., Dunn, W. B., Boocock, D. J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.27022771
Additional file 5 of Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice
Morgan, H. L., Eid, N. S., Holmes, N., Henson, S., Wright, V., Coveney, C., Winder, C. L., O’Neil, D. M., Dunn, W. B., Boocock, D. J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.27022765
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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.
ORCID: Rivas, Donato A.
McDonald, Devin J.
Rice, Nicholas P.
Dolnikowski, Gregory G.
Fielding, Roger A.
Venue: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Publisher: American Physiological Society
Published: 2016-04-01
Volume: 310
Issue: 7
Pages: R561-R569
ISSN: 0363-6119 (ISSN-L)
1522-1490
DOI: 10.1152/ajpregu.00198.2015
PMC: PMC4867383
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: bronze
doi.org
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
Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Health Sciences › Medicine › Physiology (medical) › 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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Diminished anabolic signaling response to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity

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