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).

Pages

1854–1865

Issue

6

Volume

66

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 January 20, 2021, https://neomed.omeka.net/items/show/3020.

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