Fatty liver is a common metabolic disorder in dairy cows during the transition period.
Perilipin 5 (PLIN5), a lipid droplet coat
protein, plays important roles in the development of hepatic steatosis in mice and humans. Whether PLIN5 plays a role in the development of
fatty liver in dairy cows is unknown. An in vivo study consisting of 10 healthy and 10 cows with
fatty liver was performed to harvest liver tissue and blood samples. In addition, hepatocytes isolated from calves were infected with PLIN5 overexpression adenovirus for 48 h; treated with 0, 0.6, 1.2, or 2.4 mM
nonesterified fatty acids (
NEFA) for 24 h; or infected with PLIN5 silencing adenovirus for 48 h and then treated with 1.2 mM
NEFA for 24 h. Serum concentrations of
NEFA and β-hydroxybutyrate were greater in cows with
fatty liver. Milk production and plasma
glucose concentrations were lower in cows with
fatty liver. The results revealed that PLIN5 is highly expressed in steatotic liver and localized to lipid droplets. The abundance of
fatty acid and
triacylglycerol (TAG) synthesis-related
proteins including
sterol regulatory
element binding protein-1c,
fatty acid synthase,
acetyl-coA carboxylase 1,
diacylglycerol acyltransferase 1, and
diacylglycerol acyltransferase 2 was greater in the liver of cows with
fatty liver. In contrast, the abundance of
microsomal triglyceride transfer protein (MTP),
apolipoprotein B100, and
apolipoprotein E was lower in the liver of cows with
fatty liver. Consequently, cows with
fatty liver exhibited severe hepatic TAG accumulation and lower blood concentration of
very low density lipoprotein apolipoprotein B (VLDL-
ApoB). Overexpression of PLIN5 and exogenous
NEFA in cultured hepatocytes increased the abundance of
sterol regulatory
element binding protein-1,
fatty acid synthase,
acetyl-coA carboxylase 1,
diacylglycerol acyltransferase 1, and
diacylglycerol acyltransferase 2 but decreased the abundance of
microsomal triglyceride transfer protein,
apolipoprotein B100, and
apolipoprotein E, which promoted TAG synthesis and inhibited VLDL-
ApoB assembly, inducing
lipid accumulation. Importantly, knockdown of PLIN5 attenuated the upregulation of TAG synthesis and downregulation of VLDL-
ApoB assembly induced by
NEFA. Overall, these data suggest that
NEFA activate PLIN5, leading to TAG accumulation and inhibition of VLDL assembly. As such, these mechanisms explain in part the development of hepatic steatosis in dairy cows.