S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
The orphan nuclear receptor small heterodimer partner is required for thiazolidinedione effects in leptin-deficient mice
- Tseng, Hsiu-Ting; Park, Young Joo; Lee, Yoon Kwang; Moore, David D
- Issue Date
- BioMed Central
- Journal of Biomedical Science, 22(1):30
Small heterodimer partner (SHP, NR0B2) is involved in diverse metabolic pathways, 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 leptin-deficient (ob/ob) and leptin-, SHP-deficient (ob/ob;Shp−/−) double mutant mice.
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.
Our results suggest that SHP is required for both antidiabetic and hypolipidemic effects of TZDs in ob/ob mice through regulation of PPARγ expression.