Adiponectin and Adiponectin Receptors
Abstract
Metabolic syndrome is thought to result from obesity and obesity-linked insulin resistance. Obesity in adulthood is characterized by adipocyte hypertrophy. Adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active "adipokines."Heterozygous peroxisome proliferator-activated receptor-gamma knockout mice were protected from high-fat diet induced obesity, adipocyte hypertrophy, and insulin resistance. Systematic gene profiling analysis of these mice revealed that adiponectin/Acrp30 was overexpressed. Functional analyses including generation of adiponectin transgenic or knockout mice have revealed that adiponectin serves as an insulin-sensitizing adipokine. In fact, obesity-linked down-regulation of adiponectin was a mechanism whereby obesity could cause insulin resistance and diabetes. Recently, we have cloned adiponectin receptors in the skeletal muscle (AdipoR1) and liver (AdipoR2), which appear to comprise a novel cell-surface receptor family. We showed that AdipoR1 and AdipoR2 serve as receptors for globular and full-length adiponectin and mediate increased AMP-activated protein kinase, peroxisome proliferator-activated receptor-alpha ligand activities, and glucose uptake and fatty-acid oxidation by adiponectin. Obesity decreased expression levels of AdipoR1/R2, thereby reducing adiponectin sensitivity, which finally leads to insulin resistance, the so-called "vicious cycle." Most recently, we showed that osmotin, which is a ligand for the yeast homolog of AdipoR (PHO36), activated AMPK via AdipoR in C2C12 myocytes. This may facilitate efficient development of adiponectin receptor agonists. Adiponectin receptor agonists and adiponectin sensitizers should serve as versatile treatment strategies for obesity-linked diseases such as diabetes and metabolic syndrome.
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Adiponectin reflects adipose tissue dysfunction and insulin sensitivity.
“Adiponectin reflects adipose tissue dysfunction and insulin sensitivity [8]”
Low serum adiponectin levels may cause insulin resistance in women with PCOS.
“In particular, we need to consider the role of low serum adiponectin levels in causing IR in women with PCOS as adiponectin (i) decreases muscle triglyceride content, (ii) regulates the insulin receptor, (iii) activates peroxisome proliferator-activated receptor α (PPARα) to increase fatty acid oxidation, (iv) reduces hepatic glucose production by activating protein kinases, (v) increases fat ox”
From Circulating Adipokine Levels in Nonobese Women with Polycystic Ovary Syndrome and in Nonobese Control Women: A Systematic Review and Meta-Analysis (2021) · cites this paper as [35]
Levels of adiponectin are invariably reduced in animals and humans with obesity.
“The relevance of this model stems from the fact that levels of adiponectin are invariably reduced in animals and humans with obesity (161).”
From Cardiac remodeling in obesity (2008) · cites this paper as [161]
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- Authors
- Kadowaki, T., & Yamauchi, T.
- Affiliations
- Japan Science and Technology Agency (JP)
- Corresponding author
- Kadowaki, Takashi
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2005-05-01
- Volume
- 26
- Issue
- 3
- Pages
- 439-451
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W1971452427
- Cited by
- 2,634
- References
- 103
- Citations by year
- 2026: 51 · 2025: 67 · 2024: 65 · 2023: 61 · 2022: 62 · 2021: 86 · 2020: 84 · 2019: 90 · 2018: 96 · 2017: 107 · 2016: 127 · 2015: 138 · 2014: 181 · 2013: 204 · 2012: 188
- FWCI
- 19.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kyorin Pharmaceutical
- Imperial College London
- Keio University
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (10NP0201)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- adiponectin, adiponectin receptors, AdipoR1, AdipoR2, metabolic syndrome, obesity, insulin resistance, adipokines, adipocyte hypertrophy, AMPK, PPARα, glucose uptake, fatty acid oxidation, osmotin, adiponectin receptor agonist
- MeSH terms
- Animals, Arteriosclerosis, Disease Models, Animal, Humans, Insulin Resistance, Liver, Models, Molecular, Receptors, Cell Surface, Muscle, Skeletal, Metabolic Syndrome, Intercellular Signaling Peptides and Proteins, Mice, Adiponectin, Receptors, Adiponectin
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