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

  • Schweitzer GG Washington University School of Medicine, St. Louis, MO 63110.
  • Chen Z Washington University School of Medicine, St. Louis, MO 63110.
  • Gan C Washington University School of Medicine, St. Louis, MO 63110.
  • McCommis KS Washington University School of Medicine, St. Louis, MO 63110.
  • Soufi N Washington University School of Medicine, St. Louis, MO 63110.
  • Chrast R Department of Medical Genetics, University of Lausanne, 1005 Lausanne, Switzerland.
  • Mitra MS Washington University School of Medicine, St. Louis, MO 63110.
  • Yang K Washington University School of Medicine, St. Louis, MO 63110.
  • Gross RW Washington University School of Medicine, St. Louis, MO 63110.
  • Finck BN Washington University School of Medicine, St. Louis, MO 63110.
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  • 2015-02-28
Published in:
  • Journal of lipid research. - 2015
diacylglycerol
fatty acid metabolism
insulin signaling
lipid
phospholipids
triglyceride
Alleles
Animals
Fasting
Fatty Acids
Gene Expression Regulation, Enzymologic
Hepatocytes
Liver
Mice
Nuclear Proteins
Organ Specificity
Oxidation-Reduction
Phosphatidate Phosphatase
Transcription, Genetic
Triglycerides
English 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 diacylglycerol 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.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/265272
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