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Diabetes 56:583-593, 2007
DOI: 10.2337/db06-1432
© 2007 by the American Diabetes Association
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Opposing Effects of Adiponectin Receptors 1 and 2 on Energy Metabolism

Mikael Bjursell1,2, Andrea Ahnmark1, Mohammad Bohlooly-Y1,2, Lena William-Olsson1, Magdalena Rhedin1, Xiao-Rong Peng1, Karolina Ploj1, Anna-Karin Gerdin1, Gunnel Arnerup3, Anders Elmgren1, Anna-Lena Berg3, Jan Oscarsson1,2,4, and Daniel Lindén1,4

1 AstraZeneca R&D, Mölndal, Sweden
2 Department of Physiology/Endocrinology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
3 Safety Assessment Sweden, AstraZeneca R&D, Södertälje, Sweden
4 Wallenberg Laboratory for Cardiovascular Research, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden

Address correspondence and reprint requests to Daniel Lindén, AstraZeneca R&D, Department of Integrative Pharmacology, SE-431 83 Mölndal, Sweden. E-mail: daniel.linden{at}astrazeneca.com

Abbreviations: ABCA1, ATP binding cassette transporter-1; AGRP, agouti-related peptide; AMPK, AMP-activated protein kinase; apoAI, apolipoprotein AI; BAT, brown adipose tissue; CPT-1, carnitine palmitoyl transferase-1; CRH, corticotrophin-releasing hormone; DEXA, dual-energy X-ray absorptiometry; HFD, high-fat diet; NPY, neuropeptide Y; PPAR{alpha}, peroxisome proliferator–activated receptor {alpha}; SNP, single nucleotide polymorphism; WAT, white adipose tissue

The adipocyte-derived hormone adiponectin regulates glucose and lipid metabolism and influences the risk for developing obesity, type 2 diabetes, and cardiovascular disease. Adiponectin binds to two different seven-transmembrane domain receptors termed AdipoR1 and AdipoR2. To study the physiological importance of these receptors, AdipoR1 gene knockout mice (AdipoR1–/–) and AdipoR2 gene knockout mice (AdipoR2–/–) were generated. AdipoR1–/– mice showed increased adiposity associated with decreased glucose tolerance, spontaneous locomotor activity, and energy expenditure. However, AdipoR2–/– mice were lean and resistant to high-fat diet–induced obesity associated with improved glucose tolerance and higher spontaneous locomotor activity and energy expenditure and reduced plasma cholesterol levels. Thus, AdipoR1 and AdipoR2 are clearly involved in energy metabolism but have opposing effects.


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[Abstract] [Full Text] [PDF]


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