ArticleThe Journal of cell biology2024
Tip60-mediated Rheb acetylation links palmitic acid with mTORC1 activation and insulin resistance.
Article in The Journal of cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- SRM-Mediated Spermidine Synthesis Links Lipid Overload With AMPK Pathway to Regulate Hepatic Insulin Signaling and Gluconeogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The Interaction Between Insulin Resistance and Neuroinflammation in the Brain and Its Impact on Diabetic Encephalopathy.Biology · 2026Review
- Hyperlipidemia Aggravates Alveolar Bone Loss via Periodontal Ligament Stem Cell Ferroptosis Through GSK3β Dependent Ubiquitin-Mediated NRF2 Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fetuin-b Mediates Lipid Overload-Induced Hepatic Lipid Accumulation in Large Yellow Croaker (Larimichthys crocea).FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- High Ratio of Dietary Palmitic Acid to DHA + EPA Induces Glucose Metabolic Disorder Through Endocrine and Transcriptional Regulation in Large Yellow Croaker (Metabolites · 2026Article
- Molecular and cellular mechanisms of pentadecanoic acid.World journal of biological chemistry · 2025Review
- Role of saturated fatty acid metabolism in posttranslational modifications of the Tau protein.Molecular and cellular biochemistry · 2025Review
- Acetyltransferase in cardiovascular disease and aging.The journal of cardiovascular aging · 2024Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Excess dietary intake of saturated fatty acids (SFAs) induces glucose intolerance and metabolic disorders. In contrast, unsaturated fatty acids (UFAs) elicit beneficial effects on insulin sensitivity. However, it remains elusive how SFAs and UFAs signal differentially toward insulin signaling to influence glucose homeostasis. Here, using a croaker model, we report that dietary palmitic acid (PA), but not oleic acid or linoleic acid, leads to dysregulation of mTORC1, which provokes systemic insulin resistance. Mechanistically, we show that PA profoundly elevates acetyl-CoA derived from mitochondrial fatty acid β oxidation to intensify Tip60-mediated Rheb acetylation, which triggers mTORC1 activation by promoting the interaction between Rheb and FKBPs. Subsequently, hyperactivation of mTORC1 enhances IRS1 serine phosphorylation and inhibits TFEB-mediated IRS1 transcription, inducing impairment of insulin signaling. Collectively, our results reveal a conserved molecular insight into the mechanism by which Tip60-mediated Rheb acetylation induces mTORC1 activation and insulin resistance under the PA condition, which may provide therapeutic avenues to intervene in the development of T2D.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.