Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2025 Jul 1.
Published in final edited form as: Trends Endocrinol Metab. 2024 Jun 26;35(7):674–675. doi: 10.1016/j.tem.2024.05.004

Adiponectin

Yan LI 1, Toshiharu Onodera 1,2, Philipp E Scherer 1
PMCID: PMC11374108  NIHMSID: NIHMS1995028  PMID: 38981443

graphic file with name nihms-1995028-f0001.jpg

Adiponectin (APN), also referred to as ACRP30, AdipoQ, GBP28 and APM1, is one of the most important adipokines. It is secreted from adipocytes in multimeric forms and binds to its receptors, which are widely expressed in many tissues. Cellular APN expression can be regulated by PPARγ activity and insulin levels, while its circulating level is affected by sex, BMI, age and many other factors.

graphic file with name nihms-1995028-f0002.jpg

Adiponectin is a multifaceted protein fundamentally enhancing insulin sensitivity, fatty acid oxidation, and lowering glucose and ceramide levels in an endocrine and paracrine manner, dependent on the cell type targeted and the local microenvironment within the organs. In addition, intracellular adiponectin alters lipid metabolism. AdipoR agonists improve diabetic symptoms and muscle dysfunction, suggesting the adiponectin pathway may serve as a potential therapeutic target for obesity, diabetes, and vascular dysfunction.

SIGNALING FACTS:

  • APN forms three oligomeric complexes, trimers, hexamers, and high-molecular weight (HMW) multimers. Some forms may exert functions intracellularly.

  • Adiponectin receptors (AdipoR1 and AdipoR2) exert metabolic effects through the activation of downstream PPARα,γ and AMPK pathways.

  • Adiponectin and its receptors exert potent anti-lipotoxic effects through a receptor-inherent ceramidase activity.

  • T-cadherin also binds to hexamers and HMW forms of adiponectin, but does not exert any signaling function.

  • Adiponectin is rapidly cleared by hepatocytes and other cell types, with a short half-life of around 75 minutes.

PHYSIOLOGICAL ROLE:

  • Mainly produced in adipocytes. It remains the most adipocytespecific marker.

  • However, recent reports indicate that adiponectin may also be expressed in the kidney, in hepatic stellate cells and in cardiomyocytes under specific conditions.

  • Anti-diabetic by enhancing insulin production, secretion and sensitization, promoting glucose uptake and fatty acid oxidation.

  • Alleviating apoptosis by reducing oxidative stress and attenuating inflammatory responses.

  • Anti-fibrotic through PPARγ, such as the inhibition of stellate cell activation in the liver.

  • Cardiovascular and pancreatic β-cell protective effects mediated through multiple pathways.

  • Plasma adiponectin levels decreased with obesity and diabetes.

  • Controlling brain function including food intake, energy homeostasis, neurogenesis and synaptic plasticity.

Acknowledgment

The figures were created with BioRender.com.

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Literature

  • 1.Scherer PE et al. “A novel serum protein similar to C1q, produced exclusively in adipocytes.” The Journal of biological chemistry vol. 270,45 (1995): 26746–9. doi: 10.1074/jbc.270.45.26746 [DOI] [PubMed] [Google Scholar]
  • 2.Maeda K et al. “cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1).” Biochemical and biophysical research communications vol. 221,2 (1996): 286–9. doi: 10.1006/bbrc.1996.0587 [DOI] [PubMed] [Google Scholar]
  • 3.Nakano Y et al. “Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma.” Journal of biochemistry vol. 120,4 (1996): 803–12. doi: 10.1093/oxfordjournals.jbchem.a021483 [DOI] [PubMed] [Google Scholar]
  • 4.Berg AH et al. “The adipocyte-secreted protein Acrp30 enhances hepatic insulin action.” Nature medicine vol. 7,8 (2001): 947–53. doi: 10.1038/90992 [DOI] [PubMed] [Google Scholar]
  • 5.Yamauchi T et al. “The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.” Nature medicine vol. 7,8 (2001): 941–6. doi: 10.1038/90984 [DOI] [PubMed] [Google Scholar]
  • 6.Pajvani Utpal B et al. “Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity.” The Journal of biological chemistry vol. 278,11 (2003): 9073–85. doi: 10.1074/jbc.M207198200 [DOI] [PubMed] [Google Scholar]
  • 7.Tanabe Hiroaki et al. “Crystal structures of the human adiponectin receptors.” Nature vol. 520,7547 (2015): 312–316. doi: 10.1038/nature14301 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Okada-Iwabu Miki et al. “A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity.” Nature vol. 503,7477 (2013): 493–9. doi: 10.1038/nature12656 [DOI] [PubMed] [Google Scholar]
  • 9.Achari AE, Jain SK. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int J Mol Sci. 2017. Jun 21;18(6):1321. doi: 10.3390/ijms18061321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Straub Leon G, and Scherer Philipp E. “Metabolic Messengers: Adiponectin.” Nature metabolism vol. 1,3 (2019): 334–339. doi: 10.1038/s42255-019-0041-z [DOI] [PMC free article] [PubMed] [Google Scholar]

RESOURCES