Peroxisome proliferator-activated receptor γ (pparγ)- independent specific cytotoxicity against immature adipocytes induced by pparγ antagonist T0070907

12Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) plays indispensable roles in adipogenesis, which is frequently impaired under pathological conditions such as non-alcoholic steatohepatitis (NASH). Thus, a potent PPARγ antagonist, T0070907 is known as a useful tool for understanding such pathological conditions, while T007097 was also suggested to have PPARγ-independent actions. In the present study, we found that T0070907 inhibited adipogenesis concomitantly with the induction of rapid apoptosis of immature adipocytes within 2 h, whereas another PPARγ antagonist, SR-202 did not show such cytotoxicity. However, T0070907 did not affect the viabilities of pre-adipocytes, mature adipocytes, and NIH-3T3 fibroblasts. The cytotoxic effect of T0070907 was not inhibited by GW1929, a PPARγ agonist, but was inhibited by α-tocopherol, which was previously shown to provide clinical benefit to NASH patients. Interestingly, treatment with high amounts of α-tocopherol alone slightly increased the cellular lipid content in mature adipocytes, but did not affect PPARγ-dependent luciferase reporter expression in COS-7 cells. Moreover, other lipophilic antioxidants, such as tocotrienols, tert-butylhydroquinone, and butylated hydroxyanisole, also inhibited T0070907-induced apoptosis like α-tocopherol. Consequently, it is suggested that T0070907 efficiently inhibits adipogenesis, not only via PPARγ-dependent manner, but also through the induction of apoptosis specifically against immature adipocytes via oxidative stress in a PPARγ-independent manner. © 2013 The Pharmaceutical Society of Japan.

Cite

CITATION STYLE

APA

Kawahara, A., Haraguchi, N., Tsuchiya, H., Ikeda, Y., Hama, S., & Kogure, K. (2013). Peroxisome proliferator-activated receptor γ (pparγ)- independent specific cytotoxicity against immature adipocytes induced by pparγ antagonist T0070907. Biological and Pharmaceutical Bulletin, 36(9), 1428–1434. https://doi.org/10.1248/bpb.b13-00024

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free