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Mol Endocrinol. 2015 Oct;29(10):1414-25. doi: 10.1210/me.2015-1069. Epub 2015 Aug 21.

Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance in High Fat-Fed Mice.

Author information

1
Department of Internal Medicine (M.B.T., D.M.-H., Y.M., T.K., J.N., Y.I.), Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, Virginia 23507; Department of Microbiology and Molecular Cell Biology (E.V.G.), Eastern Virginia Medical School, Norfolk, Virginia 23507; Department of Mathematics and Statistics (A.P.), Old Dominion University, Norfolk, Virginia 23529; and Leroy T. Canoles Cancer Research Center (S.D.), Eastern Virginia Medical School, Norfolk, Virginia 23507.

Abstract

Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, compared with Ad-GFP liver. Lipids commonly associated with hepatic lipotoxicity, diacylglycerol, and ceramides, were also increased in Ad-PLIN5 liver. The expression of genes in lipid metabolism regulated by peroxisome proliferator-activated receptor-α was reduced suggestive of slower mobilization of stored lipids in Ad-PLIN5 mice. However, the increase of hepatosteatosis by PLIN5 overexpression did not worsen glucose homeostasis. Rather, serum insulin levels were decreased, indicating better insulin sensitivity in Ad-PLIN5 mice. Moreover, genes associated with liver injury were unaltered in Ad-PLIN5 steatotic liver compared with Ad-GFP control. Phosphorylation of protein kinase B was increased in Ad-PLIN5-transduced AML12 hepatocyte despite of the promotion of fatty acid incorporation to triacylglycerol as well. Collectively, our data indicates that the increase in liver PLIN5 during hepatosteatosis drives further lipid accumulation but does not adversely affect hepatic health or insulin sensitivity.

PMID:
26296152
PMCID:
PMC4588733
DOI:
10.1210/me.2015-1069
[Indexed for MEDLINE]
Free PMC Article

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