PPARα is Required for PPARδ action in regulation of body weight and hepatic steatosis in mice.

Details

Serval ID
serval:BIB_F1FCCD788BB5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PPARα is Required for PPARδ action in regulation of body weight and hepatic steatosis in mice.
Journal
PPAR Research
Author(s)
Garbacz W.G., Huang J.T., Higgins L.G., Wahli W., Palmer C.N.
ISSN
1687-4765 (electronic)
Publication state
Published
Issued date
2015
Volume
2015
Pages
927057
Language
english
Abstract
Peroxisome proliferator activated receptors alpha (PPARα) and delta (PPARδ) belong to the nuclear receptor superfamily. PPARα is a target of well established lipid-lowering drugs. PPARδ (also known as PPARβ/δ) has been investigated as a promising antidiabetic drug target; however, the evidence in the literature on PPARδ effect on hepatic lipid metabolism is inconsistent. Mice conditionally expressing human PPARδ demonstrated pronounced weight loss and promoted hepatic steatosis when treated with GW501516 (PPARδ-agonist) when compared to wild type mice. This effect was completely absent in mice with either a dominant negative form of PPARδ or deletion of the DNA binding domain of PPARδ. This confirmed the absolute requirement for PPARδ in the physiological actions of GW501516 and confirmed the potential utility against the human form of this receptor. Surprisingly the genetic deletion of PPARα also abrogated the effect of GW501516 in terms of both weight loss and hepatic lipid accumulation. Also the levels of the PPARα endogenous agonist 16:0/18:1-GPC were shown to be modulated by PPARδ in wild type mice. Our results show that both PPARδ and PPARα receptors are essential for GW501516-driven adipose tissue reduction and subsequently hepatic steatosis, with PPARα working downstream of PPARδ.
Pubmed
Web of science
Open Access
Yes
Create date
07/12/2015 11:15
Last modification date
20/08/2019 17:19
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