PPARalpha governs glycerol metabolism

The Journal of Clinical Investigation
David PatsourisSander Kersten

Abstract

Glycerol, a product of adipose tissue lipolysis, is an important substrate for hepatic glucose synthesis. However, little is known about the regulation of hepatic glycerol metabolism. Here we show that several genes involved in the hepatic metabolism of glycerol, i.e., cytosolic and mitochondrial glycerol 3-phosphate dehydrogenase (GPDH), glycerol kinase, and glycerol transporters aquaporin 3 and 9, are upregulated by fasting in wild-type mice but not in mice lacking PPARalpha. Furthermore, expression of these genes was induced by the PPARalpha agonist Wy14643 in wild-type but not PPARalpha-null mice. In adipocytes, which express high levels of PPARgamma, expression of cytosolic GPDH was enhanced by PPARgamma and beta/delta agonists, while expression was decreased in PPARgamma(+/-) and PPARbeta/delta(-/-) mice. Transactivation, gel shift, and chromatin immunoprecipitation experiments demonstrated that cytosolic GPDH is a direct PPAR target gene. In line with a stimulating role of PPARalpha in hepatic glycerol utilization, administration of synthetic PPARalpha agonists in mice and humans decreased plasma glycerol. Finally, hepatic glucose production was decreased in PPARalpha-null mice simultaneously fasted and exposed to Wy1464...Continue Reading

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Citations

Apr 18, 2007·Cellular and Molecular Life Sciences : CMLS·S MandardS Kersten
Oct 6, 2009·The Journal of Biological Chemistry·Maaike H OosterveerDirk-Jan Reijngoud
Nov 15, 2011·The Journal of Biological Chemistry·Sabina JelenMichael Rützler
Feb 1, 2005·Genes & Development·Hong-Ping GuanMitchell A Lazar
Feb 6, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Saskia KleyDarin E Olson
Mar 29, 2007·PPAR Research·Rinke StienstraSander Kersten
Oct 12, 2010·PPAR Research·Maryam RakhshandehrooSander Kersten
Jul 12, 2005·The Journal of Clinical Investigation·Patricia C ChuiMitchell A Lazar
Mar 3, 2006·The Journal of Clinical Investigation·Philippe LefebvreBart Staels
Sep 25, 2010·BMC Biochemistry·Carolina GustavssonPetra Tollet-Egnell
Dec 17, 2009·BMC Genomics·Duccio CavalieriMichael Müller
Jul 26, 2007·Genome Biology·Merja HeinäniemiCarsten Carlberg
Nov 11, 2010·Amino Acids·Najoua GuelzimDominique Hermier
Aug 18, 2005·Current Atherosclerosis Reports·Giulia Chinetti-GbaguidiBart Staels
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Apr 18, 2020·Scientific Reports·Marion RégnierAlexandra Montagner
Nov 18, 2020·JCI Insight·Pegah PoursharifiMarc Prentki

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Methods Mentioned

BETA
PCR
electrophoretic mobility shift assay
immunoprecipitation
ChIP
chips
transfections
FCS
SGBS
enzymatic assay
Protein Assay

Software Mentioned

Affymetrix GeneChip3

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