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.