Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion

Xin Rong, Bo Wang, Merlow M. Dunham, Per Niklas Hedde, Jinny S. Wong, Enrico Gratton, Stephen G. Young, David A. Ford, Peter Tontonoz

Research output: Contribution to journalArticlepeer-review

Abstract

The role of specific phospholipids in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of triglyceride secretion due to its unique ability to catalyze the incorporation of arachidonate into membranes. Mice lacking Lpcat3 in the intestine fail to thrive during weaning and exhibit enterocyte lipid accumulation and reduced plasma triglycerides. Mice lacking Lpcat3 in the liver show reduced plasma triglycerides, hepatosteatosis, and secrete lipid-poor VLDL lacking arachidonoyl phospholipids. Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl phospholipids in lipidating lipoprotein particles. These data identify Lpcat3 as a key factor in lipoprotein production and illustrate how manipulation of membrane composition can be used as a regulatory mechanism to control metabolic pathways.

Original languageEnglish (US)
JournaleLife
Volume2015
Issue number4
DOIs
StatePublished - Mar 25 2015
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion'. Together they form a unique fingerprint.

Cite this