The orphan nuclear receptor small heterodimer partner is required for thiazolidinedione effects in leptin-deficient mice.

Title

The orphan nuclear receptor small heterodimer partner is required for thiazolidinedione effects in leptin-deficient mice.

Creator

Tseng Hsiu-Ting; Park Young Joo; Lee Yoon-Kwang; Moore David D

Publisher

Journal of biomedical science

Date

2015
2015-05

Description

BACKGROUND: 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 gamma (PPARgamma), 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. 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. PPARgamma2 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 PPARgamma2 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 PPARgamma expression.

Subject

Animals; Bile Acids and Salts/metabolism; Cytoplasmic and Nuclear/biosynthesis/*genetics/metabolism; Diabetes Mellitus/*drug therapy/genetics/metabolism; Gene Expression Regulation/drug effects; Glucose/metabolism; Hepatocytes/drug effects; Humans; Insulin Resistance/genetics; Insulin/*metabolism; Leptin/deficiency/genetics; Lipid Metabolism/drug effects; Messenger/genetics; Mice; Obese; PPAR gamma/*biosynthesis/genetics; Receptors; RNA; Thiazolidinediones/*administration & dosage

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

30–30

Volume

22

Citation

Tseng Hsiu-Ting; Park Young Joo; Lee Yoon-Kwang; Moore David D, “The orphan nuclear receptor small heterodimer partner is required for thiazolidinedione effects in leptin-deficient mice.,” NEOMED Bibliography Database, accessed October 27, 2021, https://neomed.omeka.net/items/show/4854.

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