ArticleMolecular metabolism2015
A major role of insulin in promoting obesity-associated adipose tissue inflammation.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 141 citations in OpenAlex.
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- Hyperinsulinaemia as a cause of obesity and cardiometabolic diseases.Nature reviews. Endocrinology · 2026Review
- How Adipocytes Orchestrate Inflammation Within Adipose Tissue?Biomolecules · 2025Review
- 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
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- Dietary and lifestyle insulinemic potentials, plasma metabolome, and risk of diverticulitis: a prospective cohort study.The American journal of clinical nutrition · 2024Article
- Therapeutic Insulin Analogue Concentrations at Infusion Sites Enhanced the Pro-Inflammatory Response and Apoptosis in an In Vitro Macrophage-Material Interaction Model.ACS pharmacology & translational science · 2024Article
- Aging and "Age-Related" Diseases - What Is the Relation?Aging and disease · 2024Review
- The predictive value of lesion-specific pericoronary fat attenuation index for major adverse cardiovascular events in patients with type 2 diabetes.Cardiovascular diabetology · 2024Article
- Research advances in the anti-inflammatory effects of SGLT inhibitors in type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2024Review
- Unraveling the complex roles of macrophages in obese adipose tissue: an overview.Frontiers of medicine · 2024Review
- The Metabolic Syndrome, a Human Disease.International journal of molecular sciences · 2024Review
- Wnt/β-Catenin Signaling Activation Induces Differentiation in Human Limbal Epithelial Stem Cells Cultured Ex Vivo.Biomedicines · 2023Article
- Serendipitous Discovery of T Cell-Produced KLK1b22 as a Regulator of Systemic Metabolism.ImmunoHorizons · 2023Article
- Article
- De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics.Nature communications · 2023Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
objectiveAdipose tissue (AT) inflammation is associated with systemic insulin resistance and hyperinsulinemia in obese rodents and humans. A longstanding concept is that hyperinsulinemia may promote systemic insulin resistance through downregulation of its receptor on target tissues. Here we tested the novel hypothesis that insulin also impairs systemic insulin sensitivity by specifically enhancing adipose inflammation.
methodsCirculating insulin levels were reduced by about 50% in diet-induced and genetically obese mice by treatments with diazoxide or streptozotocin, respectively. We then examined AT crown-like structures, macrophage markers and pro-inflammatory cytokine expression in AT. AT lipogenesis and systemic insulin sensitivity was also monitored. Conversely, insulin was infused into lean mice to determine its affects on the above parameters.
resultsLowering circulating insulin levels in obese mice by streptozotocin treatment decreased macrophage content in AT, enhancing insulin stimulated Akt phosphorylation and de novo lipogenesis (DNL). Moreover, responsiveness of blood glucose levels to injected insulin was improved by streptozotocin and diazoxide treatments of obese mice without changes in body weight. Remarkably, even in lean mice, infusion of insulin under constant euglycemic conditions stimulated expression of cytokines in AT. Consistent with these findings, insulin treatment of 3T3-L1 adipocytes caused a 10-fold increase in CCL2 mRNA levels within 6 h, which was blocked by the ERK inhibitor PD98059.
conclusionTaken together, these results indicate that obesity-associated hyperinsulinemia unexpectedly drives AT inflammation in obese mice, which in turn contributes to factors that suppress insulin-stimulated adipocyte DNL and systemic insulin sensitivity.
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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.