ArticleJCI insight2021
Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol/PKCε/insulin receptor Thr1160 phosphorylation.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 29 citations in OpenAlex.
- ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis.The Journal of clinical investigation · 2025Trial
- Insulin receptorNature communications · 2026Article
- Hypothesis: Nutrient Off-Loading and Ectopic Fat Reduction Reverse Insulin Resistance and Improve Cardiovascular Outcomes in Type 2 Diabetes-A Narrative Review.International journal of molecular sciences · 2026Review
- Insulin resistance: mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Altered Molecular Regulation of TUG Is a Central Feature of Insulin-Resistant Human Adipose Tissue.Diabetes · 2026Article
- Article
- RNF186 controls glucose metabolism in metabolic dysfunction-associated fatty liver disease.Cell & bioscience · 2025Article
- The Pivotal Role of the Western Diet, Hyperinsulinemia, Ectopic Fat, and Diacylglycerol-Mediated Insulin Resistance in Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Early prediction of postpartum dyslipidemia in gestational diabetes using machine learning models.Scientific reports · 2025Article
- Overnutrition causes insulin resistance and metabolic disorder through increased sympathetic nervous system activity.Cell metabolism · 2025Article
- Lipidomics and temporal-spatial distribution of organelle lipid.Journal of biological methods · 2025Review
- High-fat-diet-induced hepatic insulin resistanceiScience · 2024Article
- Addressing Post-Acute COVID-19 Syndrome in Cancer Patients, from Visceral Obesity and Myosteatosis to Systemic Inflammation: Implications in Cardio-Onco-Metabolism.Biomedicines · 2024Review
- Diabetes Mellitus, Energy Metabolism, and COVID-19.Endocrine reviews · 2024Review
- Inter-organ crosstalk during development and progression of type 2 diabetes mellitus.Nature reviews. Endocrinology · 2024Review
- Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies.Drug design, development and therapy · 2024Review
- Possible Mechanisms Linking Obesity, Steroidogenesis, and Skeletal Muscle Dysfunction.Life (Basel, Switzerland) · 2023Review
- Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice.Diabetologia · 2023Article
- Uncoupling hepatic insulin resistance - hepatic inflammation to improve insulin sensitivity and to prevent impaired metabolism-associated fatty liver disease in type 2 diabetes.Frontiers in endocrinology · 2023Review
- LDL Promotes Disorders in β-Cell Cholesterol Metabolism, Implications on Insulin Cellular Communication Mediated by EVs.Metabolites · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
White adipose tissue (WAT) insulin action has critical anabolic function and is dysregulated in overnutrition. However, the mechanism of short-term high-fat diet-induced (HFD-induced) WAT insulin resistance (IR) is poorly understood. Based on recent evidences, we hypothesize that a short-term HFD causes WAT IR through plasma membrane (PM) sn-1,2-diacylglycerol (sn-1,2-DAG) accumulation, which promotes protein kinase C-ε (PKCε) activation to impair insulin signaling by phosphorylating insulin receptor (Insr) Thr1160. To test this hypothesis, we assessed WAT insulin action in 7-day HFD-fed versus regular chow diet-fed rats during a hyperinsulinemic-euglycemic clamp. HFD feeding caused WAT IR, reflected by impaired insulin-mediated WAT glucose uptake and lipolysis suppression. These changes were specifically associated with PM sn-1,2-DAG accumulation, higher PKCε activation, and impaired insulin-stimulated Insr Tyr1162 phosphorylation. In order to examine the role of Insr Thr1160 phosphorylation in mediating lipid-induced WAT IR, we examined these same parameters in InsrT1150A mice (mouse homolog for human Thr1160) and found that HFD feeding induced WAT IR in WT control mice but not in InsrT1150A mice. Taken together, these data demonstrate the importance of the PM sn-1,2-DAG/PKCε/Insr Thr1160 phosphorylation pathway in mediating lipid-induced WAT IR and represent a potential therapeutic target to improve WAT insulin sensitivity.
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