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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-2-25
pubmed:abstractText
Seasonal obesity and fasting-associated hibernation are the two major metabolic events governing hepatic lipid metabolism in hibernating mammals. In this process, however, the role of the nuclear receptor known as peroxisome proliferator-activated receptor (PPAR)-alpha has not been elucidated yet. Here we show, as in human, that jerboa (Jaculus orientalis) liver expresses both active wild-type PPARalpha (PPARalpha1wt) and truncated PPARalpha forms and that the PPARalpha1wt to truncated PPARalpha2 ratio, which indicates the availability of active PPARalpha1wt, is differentially regulated during fasting-associated hibernation. Functional activation of hepatic jerboa PPARalpha, during prehibernating and hibernating states, was demonstrated by the induction of its target genes, which encode peroxisomal proteins such as acyl-CoA oxidase 1, peroxisomal membrane protein 70, and catalase, accompanied by a concomitant induction of PPARalpha thermogenic coactivator PPARgamma coactivator-1alpha. Interestingly, sustained activation of PPARalpha by its hypolipidemic ligand, ciprofibrate, abrogates the adaptive fasting response of PPARalpha during prehibernation and overinduces its target genes, disrupting the prehibernation fattening process. In striking contrast, during fasting-associated hibernation, jerboas exhibit preferential up-regulation of hepatic peroxisomal fatty acid oxidation instead of the mitochondrial pathway, which is down-regulated. Taken together, our results strongly suggest that PPARalpha is subject to a hibernation-dependent splicing regulation in response to feeding-fasting conditions, which defines the activity of PPARalpha and the activation of its target genes during hibernation bouts of jerboas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1945-7170
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
150
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1192-201
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Differential regulation of peroxisome proliferator-activated receptor (PPAR)-alpha1 and truncated PPARalpha2 as an adaptive response to fasting in the control of hepatic peroxisomal fatty acid beta-oxidation in the hibernating mammal.
pubmed:affiliation
Faculté des Sciences Gabriel, Unité Mixté de Recherche 866, Institut National de la Santé et de la Recherche Médicale, Centre de Recherche-Biochimie Métabolique et Nutritionnelle, Université de Bourgogne, Dijon, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't