Adult type 3 adenylyl cyclase-deficient mice are obese.
BACKGROUND
A recent study of obesity in Swedish men found that polymorphisms in the type 3 adenylyl cyclase (AC3) are associated with obesity, suggesting the interesting possibility that AC3 may play a role in weight control. Therefore, we examined the weight of AC3 mice over an extended period of time.


RESULTS
We discovered that AC3(-/-) mice become obese as they age. Adult male AC3(-/-) mice are about 40% heavier than wild type male mice while female AC3(-/-) are 70% heavier. The additional weight of AC3(-/-) mice is due to increased fat mass and larger adipocytes. Before the onset of obesity, young AC3(-/-) mice exhibit reduced physical activity, increased food consumption, and leptin insensitivity. Surprisingly, the obesity of AC3(-/-) mice is not due to a loss of AC3 from white adipose and a decrease in lipolysis.


CONCLUSIONS
We conclude that mice lacking AC3 exhibit obesity that is apparently caused by low locomotor activity, hyperphagia, and leptin insensitivity. The presence of AC3 in primary cilia of neurons of the hypothalamus suggests that cAMP signals generated by AC3 in the hypothalamus may play a critical role in regulation of body weight.
Wang
Zhenshan
Z
Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.
Li
Vicky
V
Chan
Guy C K
GC
Phan
Trongha
T
Nudelman
Aaron S
AS
Xia
Zhengui
Z
Storm
Daniel R
DR
D000262:Adenylyl Cyclases / Q000235:genetics* / Q000502:physiology*; D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D012737:Sex Factors
D020738:Leptin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3