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

Rong X, Wang B, Dunham MM, Hedde PN, Wong JS, Gratton E, Young SG, Ford DA, Tontonoz P - Elife (2015)

Bottom Line: Mice lacking Lpcat3 in the intestine fail to thrive during weaning and exhibit enterocyte lipid accumulation and reduced plasma TGs.Mice lacking Lpcat3 in the liver show reduced plasma TGs, hepatosteatosis, and secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl PLs.Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl PLs in lipidating lipoprotein particles.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States.

ABSTRACT
The role of specific phospholipids (PLs) 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 (TG) 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 TGs. Mice lacking Lpcat3 in the liver show reduced plasma TGs, hepatosteatosis, and secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl PLs. Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl PLs 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.

Show MeSH
Blood glucose levels and body weight in control and liver-specific Lpcat3 KO mice (LKO).DOI:http://dx.doi.org/10.7554/eLife.06557.006
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4400582&req=5

fig2s1: Blood glucose levels and body weight in control and liver-specific Lpcat3 KO mice (LKO).DOI:http://dx.doi.org/10.7554/eLife.06557.006

Mentions: Analysis of plasma lipid levels revealed lower plasma TG levels following an overnight fast in L-Lpcat3 KO mice compared to controls (Figure 2C). Levels of plasma total cholesterol and non-esterified free fatty acids (NEFA) were not different between groups. Body weight and fasting blood glucose levels were also not different between groups (Figure 2—figure supplement 1). Although total levels of plasma apolipoprotein B (apoB) were similar between groups (Figure 2D, Figure 2—figure supplement 2B), fractionation of plasma lipoproteins revealed lower levels of apoB in the VLDL fraction in L-Lpcat3 KO mice (Figure 2E, Figure 2—figure supplement 2A). Moreover, TG levels in the VLDL fraction were markedly reduced. We also observed a trend towards TG stores in the liver of L-Lpcat3 KO mice, along with histological evidence of increased lipid accumulation (Figure 2F,G).


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

Rong X, Wang B, Dunham MM, Hedde PN, Wong JS, Gratton E, Young SG, Ford DA, Tontonoz P - Elife (2015)

Blood glucose levels and body weight in control and liver-specific Lpcat3 KO mice (LKO).DOI:http://dx.doi.org/10.7554/eLife.06557.006
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400582&req=5

fig2s1: Blood glucose levels and body weight in control and liver-specific Lpcat3 KO mice (LKO).DOI:http://dx.doi.org/10.7554/eLife.06557.006
Mentions: Analysis of plasma lipid levels revealed lower plasma TG levels following an overnight fast in L-Lpcat3 KO mice compared to controls (Figure 2C). Levels of plasma total cholesterol and non-esterified free fatty acids (NEFA) were not different between groups. Body weight and fasting blood glucose levels were also not different between groups (Figure 2—figure supplement 1). Although total levels of plasma apolipoprotein B (apoB) were similar between groups (Figure 2D, Figure 2—figure supplement 2B), fractionation of plasma lipoproteins revealed lower levels of apoB in the VLDL fraction in L-Lpcat3 KO mice (Figure 2E, Figure 2—figure supplement 2A). Moreover, TG levels in the VLDL fraction were markedly reduced. We also observed a trend towards TG stores in the liver of L-Lpcat3 KO mice, along with histological evidence of increased lipid accumulation (Figure 2F,G).

Bottom Line: Mice lacking Lpcat3 in the intestine fail to thrive during weaning and exhibit enterocyte lipid accumulation and reduced plasma TGs.Mice lacking Lpcat3 in the liver show reduced plasma TGs, hepatosteatosis, and secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl PLs.Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl PLs in lipidating lipoprotein particles.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States.

ABSTRACT
The role of specific phospholipids (PLs) 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 (TG) 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 TGs. Mice lacking Lpcat3 in the liver show reduced plasma TGs, hepatosteatosis, and secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl PLs. Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl PLs 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.

Show MeSH