ArticleThe Journal of biological chemistry2013
Hypoxia-inducible factor 1α regulates a SOCS3-STAT3-adiponectin signal transduction pathway in adipocytes.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- Relationship Between Hypovitaminosis C, Obesity, and Features of Metabolic Syndrome-A Narrative Review.Nutrition reviews · 2026Review
- SOCS3 Stabilizes PARP1 to Suppress Adipogenic Transcription and Abdominal Adipogenesis in Avian.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Hypoxia-Inducible Factor 1α in Type 2 Diabetes Mellitus: Mechanisms and Therapeutic Perspectives.Biology · 2026Review
- Hypoxia signaling in the adipose tissue.Journal of molecular cell biology · 2025Review
- Therapeutic Potential of Targeting Prokineticin Receptors in Diseases.Pharmacological reviews · 2023Review
- Mechanobiology of cancer cell responsiveness to chemotherapy and immunotherapy: Mechanistic insights and biomaterial platforms.Advanced drug delivery reviews · 2023Review
- Anti-Inflammatory Effect of Ethanolic Extract fromMolecules (Basel, Switzerland) · 2023Article
- Therapeutic Role of Curcumin in Diabetes: An Analysis Based on Bioinformatic Findings.Nutrients · 2022Article
- CYP1A1, VEGFA and Adipokine Responses of Human Adipocytes Co-exposed to PCB126 and Hypoxia.Cells · 2022Article
- Metabolic reprogramming and crosstalk of cancer-related fibroblasts and immune cells in the tumor microenvironment.Frontiers in endocrinology · 2022Review
- An Explanation for the Adiponectin Paradox.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The balance of concentration between Prokineticin 2β and Prokineticin 2 modulates the food intake by STAT3 signaling.BBA advances · 2021Article
- The Key Genes Underlying Pathophysiology Association between Plaque Instability and Progression of Myocardial Infarction.Disease markers · 2021Article
- Mechanism and Basis of Traditional Chinese Medicine Against Obesity: Prevention and Treatment Strategies.Frontiers in pharmacology · 2021Review
- Review
- Homocysteine promotes hepatic steatosis by activating the adipocyte lipolysis in a HIF1α-ERO1α-dependent oxidative stress manner.Redox biology · 2020Article
- Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer's Disease.International journal of molecular sciences · 2020Review
- New role for ceramide in hypoxia and insulin resistance.World journal of gastroenterology · 2020Review
- Pathophysiological implications of hypoxia in human diseases.Journal of biomedical science · 2020Review
- Macrophage metabolic reprogramming aggravates aortic dissection through the HIF1α-ADAM17 pathwayEBioMedicine · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Obesity has been identified as a major risk factor for type 2 diabetes, characterized by insulin resistance in insulin target tissues. Hypoxia-inducible factor 1α (HIF1α) regulates pathways in energy metabolism that become dysregulated in obesity. Earlier studies revealed that HIF1α in adipose tissue is markedly elevated in high-fat diet-fed mice that are obese and insulin-resistant. Genetic ablation of HIF1α in adipose tissue decreased insulin resistance and obesity, accompanied by increased serum adiponectin levels. However, the exact mechanism whereby HIF1α regulates adiponectin remains unclear. Here, acriflavine (ACF), an inhibitor of HIF1α, induced the expression of adiponectin and reduced the expression of SOCS3 in cultured 3T3-L1 adipocytes. Mechanistic studies revealed that HIF1α suppressed the expression of adiponectin through a SOCS3-STAT3 pathway. Socs3 was identified as a novel HIF1α target gene based on chromatin immunoprecipitation and luciferase assays. STAT3 directly regulated adiponectin in vitro in cultured 3T3-L1 adipocytes. ACF was found to prevent diet-induced obesity and insulin resistance. In vivo, ACF also regulated the SOCS3-STAT3-adiponectin pathway, and inhibition of HIF1α in adipose tissue was essential for ACF to improve the SOCS3-STAT3-adiponectin pathway to counteract insulin resistance. This study provides evidence for a novel target gene and signal transduction pathway in adipocytes and indicates that inhibitors of HIF1α have potential utility for the treatment of obesity and type 2 diabetes.
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