Amyotrophy Induced by a High-Fat Diet Is Closely Related to Inflammation and Protein Degradation Determined by Quantitative Phosphoproteomic Analysis in Skeletal Muscle of C57BL/6 J Mice
Open accessAbstract
Background Ectopic fat accumulation in skeletal muscle results in dysfunction and atrophy, but the underlying molecular mechanisms remain unclear.Objective The aim of this study was to investigate the effects of a high-fat diet (HFD) in modulating the structure and energy metabolism of skeletal muscle and the underlying mechanisms in mice.Methods Four-week-old male C57BL/6 J mice (n = 30) were allowed 1 wk for acclimatization. After 6 mice with low body weight were removed from the study, the remaining 24 mice were fed with a normal-fat diet (NFD; 10% energy from fat, n = 12) or an HFD (60% energy from fat, n = 12) for 24 wk. At the end of the experiment, serum glucose and lipid concentrations were measured, and skeletal muscle was collected for atrophy analysis, inflammation measurements, and phosphoproteomic analysis.Results Compared with the NFD, the HFD increased (P < 0.05) body weight (35.8%), serum glucose (64.5%), and lipid (27.3%) concentrations, along with elevated (P < 0.05) expressions of the atrophy-related proteins muscle ring finger 1 (MURF1; 27.6%) and muscle atrophy F-box (MAFBX; 44.5%) in skeletal muscle. Phosphoproteomic analysis illustrated 64 proteins with differential degrees of phosphorylation between the HFD and NFD groups. These proteins were mainly involved in modulating cytoskeleton [adenylyl cyclase-associated protein 2 (CAP2) and actin-α skeletal muscle (ACTA1)], inflammation [NF-κB-activating protein (NKAP) and serine/threonine-protein kinase RIO3 (RIOK3)], glucose metabolism [Cdc42-interacting protein 4 (TRIP10); protein kinase C, and casein kinase II substrate protein 3 (PACSIN3)], and protein degradation [heat shock protein 90 kDa (HSP90AA1)]. The HFD-induced inhibitions of the insulin signaling pathway and activations of inflammation in skeletal muscle were verified by Western blot analysis.Conclusions Quantitative phosphoproteomic analysis in C57BL/6 J mice fed an NFD or HFD for 24 wk revealed that the phosphorylation of inflammatory proteins and proteins associated with glucose metabolism at specific serine residues may play critical roles in the regulation of skeletal muscle atrophy induced by an HFD. This work provides information regarding underlying molecular mechanisms for inflammation-induced dysfunction and atrophy in skeletal muscle.
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Mechanisms underlying HFD-induced atrophy are not fully understood, but recent experimental data suggest elevated toxic lipid metabolites and pro-inflammatory cytokines may contribute to decreased muscle mass and strength.
“For example, the mechanisms underlying HFD-induced atrophy are not fully understood, but recent experimental data suggest that multiple factors such as elevated levels of toxic lipid metabolites and pro-inflammatory cytokines may contribute to a decrease in muscle mass and strength [14].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [14]
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- Authors
- Sun, Y.-N., Huang, J.-Q., Chen, Z.-Z., Du, M., Ren, F.-Z., Luo, J., & Fang, B.
- Affiliations
- Washington State University (US)
- Beijing University of Agriculture (CN)
- Beijing Advanced Innovation Center for Food Nutrition and Human Health (CN)
- Corresponding author
- Luo, Jie
- Fang, Bing
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 150
- Issue
- 2
- Pages
- 294-302
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2980319946
- Cited by
- 22
- References
- 39
- Citations by year
- 2026: 7 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 3
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Beijing Municipal Science and Technology Commission (Z181100009318005, D171100008017003)
- National Key R&D Program of China (2017YFC1601800)
- 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
- skeletal muscle atrophy, high-fat diet, ectopic fat deposition, muscle inflammation, protein degradation, insulin signaling pathway, phosphoproteomics, MuRF1, atrogin-1, NF-κB signaling, glucose metabolism, HSP90AA1, C57BL/6J mice, energy metabolism, RIOK3
- MeSH terms
- Animals, Inflammation, Male, Mice, Inbred C57BL, Muscular Atrophy, Obesity, Phosphoproteins, Phosphorylation, Signal Transduction, Muscle, Skeletal, Proteomics, Mice, Diet, High-Fat, Proteolysis
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