Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase.
In adipocytes, hydrolysis of triglycerides results in the release of free fatty acids and glycerol. Aquaporin 7 (AQP7), a member of aquaglyceroporins, is known to permeabilize glycerol and water. We recently generated Aqp7-knockout (KO) mice and demonstrated that such mice have low plasma glycerol levels and impaired glycerol release in response to beta3-adrenergic agonist, suggesting that AQP7 acts as a glycerol gateway molecule in adipocytes for the efficient release of glycerol in vivo. Although there was no difference in body weight between WT and KO mice until 10 weeks of age, here we found that KO mice developed adult-onset obesity. The body weight and fat mass increased significantly in KO mice compared with WT mice after 12 weeks of age. Adipocytes of KO mice were large and exhibited accumulation of triglycerides compared with WT mice. The KO mice developed obesity and insulin resistance even at a young age after consumption of high-fat/high-sucrose diet. We demonstrated the enhanced glycerol kinase enzymatic activity in Aqp7-KO and -knockdown adipocytes. A series of our results indicate that AQP7 disruption elevates adipose glycerol kinase activity, accelerates triglycerides synthesis in adipocytes, and, finally, develops obesity.
Hibuse
Toshiyuki
T
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2-B5 Yamada-oka, Suita, Osaka 565-0871, Japan.
Maeda
Norikazu
N
Funahashi
Tohru
T
Yamamoto
Kaori
K
Nagasawa
Azumi
A
Mizunoya
Wataru
W
Kishida
Ken
K
Inoue
Kazuo
K
Kuriyama
Hiroshi
H
Nakamura
Tadashi
T
Fushiki
Tohru
T
Kihara
Shinji
S
Shimomura
Iichiro
I
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000367:Age Factors; D000818:Animals; D020346:Aquaporins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D005991:Glycerol Kinase / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009765:Obesity / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014280:Triglycerides / Q000096:biosynthesis
C491927:Aqp7 protein, mouse; D020346:Aquaporins; D014280:Triglycerides; D005991:Glycerol Kinase