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• W1870693709 abstract "Peroxisome proliferator activated receptors alpha (PPAR α ) and delta (PPAR δ ) belong to the nuclear receptor superfamily. PPAR α is a target of well established lipid-lowering drugs. PPAR δ (also known as PPAR β / δ ) has been investigated as a promising antidiabetic drug target; however, the evidence in the literature on PPAR δ effect on hepatic lipid metabolism is inconsistent. Mice conditionally expressing human PPAR δ demonstrated pronounced weight loss and promoted hepatic steatosis when treated with GW501516 (PPAR δ -agonist) when compared to wild type mice. This effect was completely absent in mice with either a dominant negative form of PPAR δ or deletion of the DNA binding domain of PPAR δ . This confirmed the absolute requirement for PPAR δ in the physiological actions of GW501516 and confirmed the potential utility against the human form of this receptor. Surprisingly the genetic deletion of PPAR α also abrogated the effect of GW501516 in terms of both weight loss and hepatic lipid accumulation. Also the levels of the PPAR α endogenous agonist 16:0/18:1-GPC were shown to be modulated by PPAR δ in wild type mice. Our results show that both PPAR δ and PPAR α receptors are essential for GW501516-driven adipose tissue reduction and subsequently hepatic steatosis, with PPAR α working downstream of PPAR δ ." @default.
• W1870693709 created "2016-06-24" @default.
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• W1870693709 date "2015-01-01" @default.
• W1870693709 modified "2023-10-15" @default.
• W1870693709 title "PPAR<i>α</i>Is Required for PPAR<i>δ</i>Action in Regulation of Body Weight and Hepatic Steatosis in Mice" @default.
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• W1870693709 doi "https://doi.org/10.1155/2015/927057" @default.
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