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Adiponectin and adiponectin receptors.
Takashi Kadowaki1, Toshimasa Yamauchi
1Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. kadowaki-3im@h.u-tokyo.ac.jp
Endocrine Reviews
|May 18, 2005
Summary
Metabolic syndrome and diabetes are linked to obesity and insulin resistance. Adiponectin, an adipokine, and its receptors (AdipoR1/R2) play crucial roles in improving insulin sensitivity, offering potential therapeutic targets.
Area of Science:
- Endocrinology
- Metabolic Research
- Molecular Biology
Background:
- Metabolic syndrome is associated with obesity and insulin resistance.
- Adipose tissue functions as an endocrine organ, secreting adipokines that regulate energy homeostasis.
- Obesity in adults often involves adipocyte hypertrophy.
Purpose of the Study:
- To investigate the role of adiponectin and its receptors in obesity-linked insulin resistance.
- To explore potential therapeutic strategies for metabolic syndrome and diabetes.
Main Methods:
- Gene profiling in heterozygous peroxisome proliferator-activated receptor-gamma knockout mice.
- Generation and analysis of adiponectin transgenic and knockout mice.
- Cloning and functional characterization of adiponectin receptors (AdipoR1 and AdipoR2).
Main Results:
- Heterozygous peroxisome proliferator-activated receptor-gamma knockout mice showed protection against diet-induced obesity and insulin resistance, with overexpression of adiponectin.
- Adiponectin was identified as an insulin-sensitizing adipokine, with its down-regulation contributing to obesity-induced insulin resistance.
- AdipoR1 and AdipoR2 mediate adiponectin's effects on glucose uptake and fatty-acid oxidation; their decreased expression in obesity reduces adiponectin sensitivity, creating a vicious cycle.
- Osmotin was shown to activate AMPK via AdipoR, suggesting potential for receptor agonist development.
Conclusions:
- Adiponectin and its receptors are critical in maintaining insulin sensitivity and preventing metabolic dysfunction.
- Therapeutic strategies targeting adiponectin receptor agonists and adiponectin sensitizers hold promise for treating obesity-related diseases like diabetes and metabolic syndrome.