- 作者: Hsiu-Ting Tseng, Young Joo Park, Yoon Kwang Lee, David D Moore
- 作者服務機構: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
- 中文摘要: --
- 英文摘要:
Background:
Small heterodimer partner (SHP, NR0B2) is involved in diverse metabolic pathwa ys, including hepatic bile acid, lipid and glucose homeostasis, and has been implicated in effects on the peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and the receptor for antidiabetic drugs thiazolidinediones (TZDs). In this study, we aim to investigate the role of SHP in TZD response by comparing TZD-treated leptindeficient (ob/ob) and leptin-, SHP-deficient (ob/ob;Shp−/−) double mutant mice.
Results:
Both ob/ob and double mutant ob/ob;Shp−/− mice developed hyperglycemia, insulin resistance, and hyperlipidemia, but hepatic fat accumulation was decreased in the double mutant ob/ob;Shp−/− mice. PPARγ2 mRNA levels were markedly lower in ob/ob;Shp−/− liver and decreased to a lesser extent in adipose tissue. The TZD troglitazone did not reduce glucose or circulating triglyceride levels in ob/ob;Shp−/− mice. Expression of the adipocytokines, such as adiponectin and resistin, was not stimulated by troglitazone treatment. Expression of hepatic lipogenic genes was also reduced in ob/ob;Shp−/− mice.Moreover, overexpression of SHP by adenovirus infection increased PPARγ2 mRNA levels in mouse primary hepatocytes.
Conclusions:
Our results suggest that SHP is required for both antidiabetic and hypolipidemic effects of TZDs in ob/ob mice through regulation of PPARγ expression. - 中文關鍵字: --
- 英文關鍵字: SHP, Troglitazone, PPARγ, Thiazolidinedione