Effects of benzbromarone and allopurinol on adiponectin in vivo and in vitro.
When treating gout patients, we have incidentally found elevated serum levels of adiponectin in some after administration of benzbromarone. In the present study, we determined whether benzbromarone increases the serum level of adiponectin in gout patients and investigated the mechanism involved. Sixty-nine patients with gout were separated into two groups, and then treated for 1 year with uric acid-lowering therapy using benzbromarone or allopurinol. After overnight fasting, blood samples were drawn before and at 1 year after beginning of treatment. In an in vitro study, 3T3L1 cells were incubated in medium containing benzbromarone, allopurinol, pioglitazone, or uric acid, after which real time PCR assays were performed for messenger RNA of adiponectin, aP2, and CD36. Furthermore, 3T3L1 cells were incubated in medium containing GW9662 (PPARgamma antagonist) together with benzbromarone or pioglitazone, after which real-time PCR assays were performed for messenger RNA of adiponectin. In the in vivo study, benzbromarone increased the serum concentration of adiponectin in the subjects, whereas allopurinol did not. In vitro, benzbromarone and pioglitazone each increased the levels of messenger RNA of adiponectin, aP2, and CD36 in 3T3 cells, whereas allopurinol and uric acid did not. Also, GW9662 suppressed the increase in adiponectin mRNA induced by benzbromarone as well as that by pioglitazone. Together, our results suggest that benzbromarone enhances the production of adiponectin via activation of PPARgamma, which is a weak agonist for PPARgamma.
Inokuchi
T
T
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Tsutsumi
Z
Z
Takahashi
S
S
Ka
T
T
Yamamoto
A
A
Moriwaki
Y
Y
Masuzaki
H
H
Yamamoto
T
T
D041721:3T3-L1 Cells; D052242:Adiponectin / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000493:Allopurinol / Q000008:administration & dosage*; D000818:Animals; D001553:Benzbromarone / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects*; D006073:Gout / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism
D052242:Adiponectin; D047495:PPAR gamma; D001553:Benzbromarone; D000493:Allopurinol