ArticlePloS one2018
Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Role and mechanism of palmitic acid-regulated palmitoylation modification of SEC63 protein during endoplasmic reticulum stress in human ovarian granulosa tumor cells (KGN).Journal of ovarian research · 2026Article
- Muscle Insulin Resistance Elicits Muscle Atrophy in Obesity.Current obesity reports · 2025Review
- The multifaceted roles of fatty acids and their dysregulation in obese mothers: potential implications for infant development.Nutrition & metabolism · 2025Review
- IPMK modulates FFA-induced insulin resistance in primary mouse hepatocytes.bioRxiv : the preprint server for biology · 2023Article
- Article
- Palmitic Acid Inhibits Myogenic Activity and Expression of Myosin Heavy Chain MHC IIb in Muscle Cells through Phosphorylation-Dependent MyoD Inactivation.International journal of molecular sciences · 2023Article
- Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress.Journal of ginseng research · 2022Article
- Pathophysiological mechanisms leading to muscle loss in chronic kidney disease.Nature reviews. Nephrology · 2022Review
- An Overview of Methods for Detecting eIF2α Phosphorylation and the Integrated Stress Response.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Increased Expression of Syncytin-1 in Skeletal Muscle of Humans With Increased Body Mass Index.Frontiers in physiology · 2022Article
- Saturated Fatty Acid-Induced Endoplasmic Reticulum Stress and Insulin Resistance Are Prevented by Imoxin in C2C12 Myotubes.Frontiers in physiology · 2022Article
- Nicotinamide N-methyltransferase upregulation via the mTORC1-ATF4 pathway activation contributes to palmitate-induced lipotoxicity in hepatocytes.American journal of physiology. Cell physiology · 2021Article
- Protection of palmitic acid treatment in RAW264.7 cells and BALB/c mice duringJournal of veterinary science · 2021Article
- Minocycline Treatment Reduces Mass and Force Output From Fast-Twitch Mouse Muscles and Inhibits Myosin Production in C2C12 Myotubes.Frontiers in physiology · 2021Article
- Article
- Omega-3 Polyunsaturated Fatty Acids Mitigate Palmitate-Induced Impairments in Skeletal Muscle Cell Viability and Differentiation.Frontiers in physiology · 2020Article
- The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- Phlorotannins fromMarine drugs · 2019Article
- Metabolites as regulators of insulin sensitivity and metabolism.Nature reviews. Molecular cell biology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4). Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory indicators of TLR4 activation (IL-6 and TNFα) and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.
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Registered trials
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