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

Détails

ID Serval
serval:BIB_0019909F9C49
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Liver-specific loss of lipin-1-mediated phosphatidic acid phosphatase activity does not mitigate intrahepatic TG accumulation in mice.
Périodique
Journal of Lipid Research
Auteur(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
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
56
Numéro
4
Pages
848-858
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
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
Oui
Création de la notice
28/04/2015 18:01
Dernière modification de la notice
08/05/2019 13:37
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