Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice

• Published in: Diabetologia Vol. 57; no. 5; pp. 1027 - 1036
• Main Authors: Qiao, Liping, Yoo, Hyung sun, Bosco, Chris, Lee, Bonggi, Feng, Gen-Sheng, Schaack, Jerome, Chi, Nai-Wen, Shao, Jianhua
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2014; Springer; Springer Nature B.V
• Subjects: Adenoviruses; Adipocytes; Adipocytes - cytology; Adiponectin - metabolism; Adiponectin - physiology; Adipose Tissue, Brown - metabolism; Adrenergic receptors; Animals; Biological and medical sciences; Body fat; Body Temperature; Citrate (si)-Synthase - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy; Energy Metabolism; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gene expression; Gene Expression Regulation; Human Physiology; Internal Medicine; Ion Channels - metabolism; Kinases; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; Oxygen Consumption; Proteins; Temperature; Thermogenesis; Time Factors; Uncoupling Protein 1; La Jolla California; United States > US; Energy expenditure; Brown adipose tissue; Thermogenesis; Adiponectin; Endocrinopathy; Vertebrata; Mammalia; Mouse; Animal; Diabetes mellitus; Rodentia; Adipokine
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-014-3180-5

Aims/hypothesis Adiponectin is an adipocyte-derived hormone that plays an important role in energy homeostasis. The main objective of this study was to investigate whether or not adiponectin regulates brown adipose tissue (BAT) activation and thermogenesis. Methods Core body temperatures (CBTs) of genetic mouse models were monitored at room temperature and during cold exposure. Cultured brown adipocytes and viral vector-mediated gene transduction were used to study the regulatory effects of adiponectin on Ucp1 gene expression and the underlying mechanisms. Results The CBTs of adiponectin knockout mice ( Adipoq −/− ) were significantly higher than those of wild type (WT) mice both at room temperature and during the cold (4°C) challenge. Conversely, reconstitution of adiponectin in Adipoq −/− mice significantly blunted β adrenergic receptor agonist-induced thermogenesis of interscapular BAT. After 10 days of intermittent cold exposure, Adipoq −/− mice exhibited higher UCP1 expression and more brown-like structure in inguinal fat than WT mice. Paradoxically, we found that the anti-thermogenic effect of adiponectin requires neither AdipoR1 nor AdipoR2, two well-known adiponectin receptors. In sharp contrast to the anti-thermogenic effects of adiponectin, AdipoR1 and especially AdipoR2 promote BAT activation. Mechanistically, adiponectin was found to inhibit Ucp1 gene expression by suppressing β 3 -adrenergic receptor expression in brown adipocytes. Conclusions/interpretation This study demonstrates that adiponectin suppresses thermogenesis, which is likely to be a mechanism whereby adiponectin reduces energy expenditure.