Opposing effects of adiponectin receptors 1 and 2 on energy metabolism.
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.
Bjursell
Mikael
M
AstraZeneca R&D, Department of Integrative Pharmacology, SE-431 83 Mölndal, Sweden.
Ahnmark
Andrea
A
Bohlooly-Y
Mohammad
M
William-Olsson
Lena
L
Rhedin
Magdalena
M
Peng
Xiao-Rong
XR
Ploj
Karolina
K
Gerdin
Anna-Karin
AK
Arnerup
Gunnel
G
Elmgren
Anders
A
Berg
Anna-Lena
AL
Oscarsson
Jan
J
Lindén
Daniel
D
D055372:AMP-Activated Protein Kinases; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005247:Feeding Behavior; D005260:Female; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009097:Multienzyme Complexes / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013737:Testis / Q000166:cytology; D013997:Time Factors
D009097:Multienzyme Complexes; D047493:PPAR alpha; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose