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Title: PPARš›¼ Is Required for PPARš›æ Action in Regulation of Body Weight and Hepatic Steatosis in Mice
Authors: Garbacz, Wojciech G.
Huang, Jeffrey T. J.
Higgins, Larry G.
Wahli, Walter
Palmer, Colin N. A.
Keywords: Medicine
Issue Date: 2015
Source: Garbacz, W. G., Huang, J. T. J., Higgins, L. G., Wahli, W., & Palmer, C. N. A. (2015). PPARĪ± Is Required for PPARĪ“ Action in Regulation of Body Weight and Hepatic Steatosis in Mice. PPAR Research, 2015, 927057-.
Series/Report no.: PPAR Research
Abstract: Peroxisome proliferator activated receptors alpha (PPARĪ±) and delta (PPARĪ“) belong to the nuclear receptor superfamily. PPARĪ± is a target of well established lipid-lowering drugs. PPARĪ“ (also known as PPARĪ²/Ī“) has been investigated as a promising antidiabetic drug target; however, the evidence in the literature on PPARĪ“ effect on hepatic lipid metabolism is inconsistent. Mice conditionally expressing human PPARĪ“ demonstrated pronounced weight loss and promoted hepatic steatosis when treated with GW501516 (PPARĪ“-agonist) when compared to wild type mice. This effect was completely absent in mice with either a dominant negative form of PPARĪ“ or deletion of the DNA binding domain of PPARĪ“. This confirmed the absolute requirement for PPARĪ“ in the physiological actions of GW501516 and confirmed the potential utility against the human form of this receptor. Surprisingly the genetic deletion of PPARĪ± also abrogated the effect of GW501516 in terms of both weight loss and hepatic lipid accumulation. Also the levels of the PPARĪ± endogenous agonist 16:0/18:1-GPC were shown to be modulated by PPARĪ“ in wild type mice. Our results show that both PPARĪ“ and PPARĪ± receptors are essential for GW501516-driven adipose tissue reduction and subsequently hepatic steatosis, with PPARĪ± working downstream of PPARĪ“.
ISSN: 1687-4757
DOI: 10.1155/2015/927057
Rights: Ā© 2015 Wojciech G. Garbacz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles


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