Liver-specific loss of lipin-1-mediated phosphatidic acid phosphatase activity does not mitigate intrahepatic TG accumulation in mice.

Details

Serval ID
serval:BIB_0019909F9C49
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Liver-specific loss of lipin-1-mediated phosphatidic acid phosphatase activity does not mitigate intrahepatic TG accumulation in mice.
Journal
Journal of Lipid Research
Author(s)
Schweitzer G.G., Chen Z., Gan C., McCommis K.S., Soufi N., Chrast R., Mitra M.S., Yang K., Gross R.W., Finck B.N.
ISSN
0022-2275 (Print)
ISSN-L
0022-2275
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
56
Number
4
Pages
848-858
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
Lipin proteins (lipin 1, 2, and 3) regulate glycerolipid homeostasis by acting as phosphatidic acid phosphohydrolase (PAP) enzymes in the TG synthesis pathway and by regulating DNA-bound transcription factors to control gene transcription. Hepatic PAP activity could contribute to hepatic fat accumulation in response to physiological and pathophysiological stimuli. To examine the role of lipin 1 in regulating hepatic lipid metabolism, we generated mice that are deficient in lipin-1-encoded PAP activity in a liver-specific manner (Alb-Lpin1(-/-) mice). This allele of lipin 1 was still able to transcriptionally regulate the expression of its target genes encoding fatty acid oxidation enzymes, and the expression of these genes was not affected in Alb-Lpin1(-/-) mouse liver. Hepatic PAP activity was significantly reduced in mice with liver-specific lipin 1 deficiency. However, hepatocytes from Alb-Lpin1(-/-) mice had normal rates of TG synthesis, and steady-state hepatic TG levels were unaffected under fed and fasted conditions. Furthermore, Alb-Lpin1(-/-) mice were not protected from intrahepatic accumulation of diacylglyerol and TG after chronic feeding of a diet rich in fat and fructose. Collectively, these data demonstrate that marked deficits in hepatic PAP activity do not impair TG synthesis and accumulation under acute or chronic conditions of lipid overload.
Pubmed
Web of science
Open Access
Yes
Create date
28/04/2015 17:01
Last modification date
20/08/2019 12:22
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