Adiponectin Signaling in Metabolic Regulation and Health
Summary
Adiponectin is an adipocyte-derived hormone with pleiotropic effects on energy balance, glucose homeostasis and vascular integrity. Circulating levels of adiponectin correlate inversely with insulin resistance, type 2 diabetes and cardiovascular disease, reflecting its role as both a biomarker and a bioactive regulator. Engagement of its receptors on liver, muscle and endothelial cells triggers activation of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor pathways and anti-inflammatory cascades. These pathways enhance fatty acid oxidation, suppress gluconeogenesis and attenuate inflammatory signalling, thereby improving systemic insulin sensitivity and protecting against vascular remodelling. The receptor repertoire, signalling intermediates and the balance between globular and multimeric forms of adiponectin collectively determine tissue-specific outcomes. Emerging evidence highlights crosstalk with insulin, nutrient-sensing and stress-response networks, underscoring adiponectin’s integrative role in maintaining metabolic health. Translational efforts aim to harness receptor agonists and lifestyle interventions to restore adiponectin signalling in metabolic disorders, with potential benefits spanning glycaemic control, retinopathy prevention and atheroprotection.
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Adiponectin Signaling in Metabolic Regulation and Health publication trend
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Technical terms
AdipoR1/AdipoR2: Cell-surface receptors for adiponectin that initiate distinct intracellular signalling cascades.
AMP-activated protein kinase (AMPK): A central metabolic sensor that responds to energy stress by promoting catabolic pathways and inhibiting anabolic processes.
Early growth response factor 4 (EGR4): A transcription factor upregulated downstream of AMPK activation and implicated in cellular stress responses.
Globular vs multimeric adiponectin: Structural isoforms of adiponectin differing in molecular weight and bioactivity, with high-molecular-weight forms often exhibiting enhanced insulin-sensitising effects.
Insulin sensitivity: The capacity of tissues to respond to insulin, promoting glucose uptake and suppressing hepatic glucose production.
References
- Small-molecule agonist AdipoRon alleviates diabetic retinopathy through the AdipoR1/AMPK/EGR4 pathway. Journal of Translational Medicine (2024).
- Adiponectin signaling and function in insulin target tissues. Journal of Molecular Cell Biology (2016).
- Adiponectin: Structure, Physiological Functions, Role in Diseases, and Effects of Nutrition. Nutrients (2021).
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