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PPARα‐dependent induction of the energy homeostasis‐regulating nuclear receptor NR1i3 (CAR) in rat hepatocytes: Potential role in starvation adaptation
Author(s) -
Wieneke Nadine,
Hirsch-Ernst Karen I.,
Kuna Manuela,
Kersten Sander,
Püschel Gerhard P.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.11.011
Subject(s) - nuclear receptor , energy homeostasis , transcription factor , homeostasis , medicine , endocrinology , agonist , hormone , receptor , constitutive androstane receptor , peroxisome proliferator activated receptor , chemistry , biology , microbiology and biotechnology , gene , biochemistry
A tight hormonal control of energy homeostasis is of pivotal relevance for animals. Recent evidence suggests an involvement of the nuclear receptor NR1i3 (CAR). Fasting induces CAR by largely unknown mechanisms and CAR‐deficient mice are defective in fasting adaptation. In rat hepatocytes CAR was induced by WY14643, a PPARα‐agonist. A DR1 motif in the CAR promoter was necessary and sufficient for this control. The PPARα‐dependent increase in CAR potentiated the phenobarbital‐induced transcription of the prototypical CAR‐dependent gene CYP2B1. Since free fatty acids are natural ligands for PPARα, a fasting‐induced increase in free fatty acids might induce CAR. In accordance with this hypothesis, CAR induction by fasting was abrogated in PPARα‐deficient mice.