ArticleNature communications2017
Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin signaling in obesity.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- The coordinated actions of metformin in the intestine and liver improves hyperglycemia.Cell reports · 2026Article
- Metabolic Endotoxemia Amplifies Estrogen Signaling Through Stromal Crosstalk in Obesity-Associated Breast Cancer.International journal of molecular sciences · 2026Article
- Novel multifunctional composite cryogel with high-performance and rapid fat-lowering efficacy via the synergy of fat digestion blockage and synthesis inhibition.Bioactive materials · 2026Article
- P300 in Inflammation: An Updated Perspective on Its Molecular Mechanisms and Therapeutic Potential.Inflammation · 2026Review
- A Global Perspective on Metabolic Dysfunction-Associated Steatotic Liver Disease: From Molecular Mechanisms to Therapeutic Strategy Innovation.Nutrients · 2026Review
- Ep300-mediated acetylation plasticity in the acetyl-CoA metabolic network drives the protective role of intensive lifestyle intervention in visceral white adipose tissue.Cell communication and signaling : CCS · 2026Article
- Christensenella tenuis alleviates endotoxemia and metabolic disorders via inhibition of intestinal lipopolysaccharide translocation.Science China. Life sciences · 2025Article
- The beneficial effect of hepatic ER stress-associated protein PDI on obesity-associated glucose dysregulation.Nutrition & metabolism · 2025Article
- Unraveling the Role of Metabolic Endotoxemia in Accelerating Breast Tumor Progression.Biomedicines · 2025Article
- Role of Protein Lysine Acetylation in the Pathogenesis and Treatment of Obesity and Metabolic Syndrome.Current obesity reports · 2025Review
- Neddylation of insulin receptor substrate acts as a bona fide regulator of insulin signaling and its implications for cancer cell migration.Cancer gene therapy · 2024Article
- Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.Cellular and molecular life sciences : CMLS · 2024Article
- The role of acetylation in obesity-induced cardiac metabolic alterations.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- Blocking AMPKαS496 phosphorylation improves mitochondrial dynamics and hyperglycemia in aging and obesity.Cell chemical biology · 2023Article
- Acetylation of p65Redox biology · 2023Article
- Review
- Far-western Blotting Detection of the Binding of Insulin Receptor Substrate to the Insulin Receptor.Bio-protocol · 2023Article
- Regulation of Liver Glucose and Lipid Metabolism by Transcriptional Factors and Coactivators.Life (Basel, Switzerland) · 2023Review
- SIRT3 alleviates imiquimod-induced psoriatic dermatitis through deacetylation of XBP1s and modulation of TLR7/8 inducing IL-23 production in macrophages.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Diabetes and obesity are characterized by insulin resistance and chronic low-grade inflammation. An elevated plasma concentration of lipopolysaccharide (LPS) caused by increased intestinal permeability during diet-induced obesity promotes insulin resistance in mice. Here, we show that LPS induces endoplasmic reticulum (ER) stress and protein levels of P300, an acetyltransferase involved in glucose production. In high-fat diet fed and genetically obese ob/ob mice, P300 translocates from the nucleus into the cytoplasm of hepatocytes. We also demonstrate that LPS activates the transcription factor XBP1 via the ER stress sensor IRE1, resulting in the induction of P300 which, in turn, acetylates IRS1/2, inhibits its association with the insulin receptor, and disrupts insulin signaling. Pharmacological inhibition of P300 acetyltransferase activity by a specific inhibitor improves insulin sensitivity and decreases hyperglycemia in obese mice. We suggest that P300 acetyltransferase activity may be a promising therapeutic target for the treatment of obese patients.Elevated plasma LPS levels have been associated with insulin resistance. Here Cao et al. show that LPS induces ER stress and P300 activity via the XBP1/IRE1 pathway. P300 acetylates IRS1/2 and inhibits its binding with the insulin receptor. The consequent impairment of insulin signaling can be rescued by pharmacological inhibition of P300.
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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.