PPARalpha governs glycerol metabolism.

Patsouris, David; Mandard, Stéphane; Voshol, Peter J; Escher, Pascal; Tan, Nguan Soon; Havekes, Louis M; Koenig, Wolfgang; März, Winfried; Tafuri, Sherrie; Wahli, Walter; Müller, Michael; Kersten, Sander (2004). PPARalpha governs glycerol metabolism. Journal of clinical investigation, 114(1), pp. 94-103. American Society for Clinical Investigation 10.1172/JCI20468

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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 Wy14643, suggesting that the stimulatory effect of PPARalpha on gluconeogenic gene expression was translated at the functional level. Overall, these data indicate that PPARalpha directly governs glycerol metabolism in liver, whereas PPARgamma regulates glycerol metabolism in adipose tissue.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Escher, Pascal

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

PD Dr. Pascal Escher

Date Deposited:

11 Jul 2017 07:39

Last Modified:

31 Jul 2017 08:31

Publisher DOI:

10.1172/JCI20468

PubMed ID:

15232616

BORIS DOI:

10.7892/boris.101774

URI:

https://boris.unibe.ch/id/eprint/101774

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