This Article Full Text Full Text (PDF) All Versions of this Article: 147/8/3835    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chihara, Y. Articles by Ogihara, T. Search for Related Content PubMed PubMed Citation Articles by Chihara, Y. Articles by Ogihara, T.

Klotho Protein Promotes Adipocyte Differentiation

Department of Geriatric Medicine (Y.C., H.R., K.I., M.I., Y.M., J.O., I.K., T.O.), Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and Department of General Medicine (K.I.), Osaka University Hospital, Osaka 565-0871, Japan

Address all correspondence and requests for reprints to: Hiromi Rakugi, M.D., Ph.D., Department of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Number B6, Suita, Osaka 565-0871, Japan. E-mail: rakugi{at}geriat.med.osaka-u.ac.jp.

Mice with homozygous disruption of the klotho exhibit multiple age-related disorders and have barely detectable amounts of white adipose tissue. Although klotho expression in cultured adipocytes has been reported, little is known about its function in adipocytes. In the present study, we investigated the role of klotho on adipocyte differentiation. Adipocyte differentiation was induced by incubation of confluent 3T3-L1 cells with insulin, dexamethasone, and 1-methyl-3-isobutyl-xanthin. Klotho-siRNA and expression vector were produced for klotho suppression and overexpression, respectively. Klotho protein was purified for determination of the hormonal effect of klotho. Klotho mRNA and protein expression increased up to the 3rd d of differentiation. A peroxisome proliferator-activated receptor- agonist increased klotho expression during the early period of adipocyte differentiation. The mRNA expression of adipocyte differentiation markers, such as CCAAT/enhancer-binding protein (C/EBP), C/EBPß, C/EBP, peroxisome proliferator-activated receptor-, and fatty acid binding protein 4, was decreased by klotho suppression, and increased 1.9- to 3.8-fold by klotho overexpression. The results of Oil Red O staining also suggested that klotho overexpression promoted adipocyte differentiation. Klotho protein stimulation resulted in a 2.4- to 4.6-fold increase in mRNA expression of differentiation markers compared with control, and the time course depended on adipocyte induction status. Western blot analysis showed that protein levels of C/EBP and C/EBP were increased by Klotho protein stimulation. These results suggest that klotho works as a hormonal factor to promote adipocyte differentiation in the early days, during the period of transient proliferation in the differentiation process, and that klotho may play an essential role in adipocyte differentiation.

This article has been cited by other articles:

				T. Bonome, D. A. Levine, J. Shih, M. Randonovich, C. A. Pise-Masison, F. Bogomolniy, L. Ozbun, J. Brady, J. C. Barrett, J. Boyd, et al. A Gene Signature Predicting for Survival in Suboptimally Debulked Patients with Ovarian Cancer Cancer Res., July 1, 2008; 68(13): 5478 - 5486. [Abstract] [Full Text] [PDF]