Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice.
Title
Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice.
Creator
Akinrotimi Oludemilade; Riessen Ryan; VanDuyne Philip; Park Jung Eun; Lee Yoon-Kwang; Wong Lee-Jun; Zavacki Ann M; Schoonjans Kristina; Anakk Sayeepriyadarshini
Publisher
Hepatology (Baltimore, Md.)
Date
2017
2017-12
Description
Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are important regulators of bile acid, lipid, and glucose homeostasis. Here, we show that global Fxr (-/-) Shp(-/-) double knockout (DKO) mice are refractory to weight gain, glucose intolerance, and hepatic steatosis when challenged with high-fat diet. DKO mice display an inherently increased capacity to burn fat and suppress de novo hepatic lipid synthesis. Moreover, DKO mice were also very active and that correlated well with the observed increase in phosphoenolpyruvate carboxykinase expression, type IA fibers, and mitochondrial function in skeletal muscle. Mechanistically, we demonstrate that liver-specific Shp deletion protects against fatty liver development by suppressing expression of peroxisome proliferator-activated receptor gamma 2 and lipid-droplet protein fat-specific protein 27 beta. CONCLUSION: These data suggest that Fxr and Shp inactivation may be beneficial to combat diet-induced obesity and uncover that hepatic SHP is necessary to promote fatty liver disease. (Hepatology 2017;66:1854-1865).
Subject
Animals; Body Weight/genetics; Cytoplasmic and Nuclear/*physiology; Diabetes Mellitus; Fatty Liver/*genetics; Knockout; Lipid Metabolism/genetics; Mice; Receptors; Type 2/*genetics
Identifier
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).
Citation
Akinrotimi Oludemilade; Riessen Ryan; VanDuyne Philip; Park Jung Eun; Lee Yoon-Kwang; Wong Lee-Jun; Zavacki Ann M; Schoonjans Kristina; Anakk Sayeepriyadarshini, “Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice.,” NEOMED Bibliography Database, accessed March 19, 2024, https://neomed.omeka.net/items/show/3020.