Lipid Accumulation and Injury in Primary Calf Hepatocytes Challenged With Different Long-Chain Fatty Acids

Bingbing Zhang,Wei Yang,Zhihao Dong,Yingying Zhao,Chuang Xu,Xinru Ma,Cheng Xia,Runqi Liu,Shuang Wang,Juan J Loor

doi:10.3389/fvets.2020.547047

Abstract

Fatty liver disease is one of the most common disorders afflicting dairy cows during the postpartum period, and is associated with increased blood non-esterified fatty acid (NEFA) uptake by the liver. Major long-chain fatty acids (LCFA) in NEFA are palmitic (PA), palmitoleic (POA), stearic (SA), oleic (OA), and linoleic (LA) acid. In order to investigate the characteristics of lipid accumulation and injury caused by these NEFA, primary calf hepatocytes were isolated and challenged for 12 h with 1.2 mmol/L PA, POA, SA, OA, LA, or a mixture of these LCFA (NEFA). Compared with POA, OA, and LA, culture with PA and SA led to greater abundance of CCAAT-enhancer binding protein, glucose-regulated protein 78 mRNA, and stearoyl-CoA desaturase 1 mRNA along with greater concentrations of H2O2, malondialdehyde and reactive oxygen species (ROS). Although culture with POA, OA, and LA led to lower very low density lipoprotein (VLDL) concentration in cell culture medium, POA and OA led to greater concentrations of triacylglycerol, protein abundance of sterol regulatory element-binding protein 1c, fatty acid synthase, acetyl coenzyme A carboxylase 1, ApoB100, and sortilin 1 (SORT1). Compared with individual fatty acids, culture with NEFA led to an intermediate degree of lipid accumulation and hepatocytes damage. Overall, the data suggest that saturated fatty acids cause more severe oxidative and ER stress. However, unsaturated fatty acids cause serious lipid accumulation. Furthermore, a fatty acid balanced nutrient regulation was suggested useful improve liver health of transition period dairy cows.

Highlights

Negative energy balance (NEB) is a subhealthy state commonly experienced by transition period cows as a consequence of insufficient dry matter intake to sustain the high energy requirements for maintenance of body functions and milk production
Fatty liver is characterized by high plasma nonesterified fatty acid (NEFA) concentrations and occurs most frequently during periods of NEB
In vitro studies with HepG2, HuH7, and WRL68 hepatocytes indicated that elevated supply of exogenous oleic acid and palmitic acid caused hepatic steatosis and hepatocyte damage [24]

Summary

Introduction

Negative energy balance (NEB) is a subhealthy state commonly experienced by transition period cows as a consequence of insufficient dry matter intake to sustain the high energy requirements for maintenance of body functions and milk production. Fatty liver is the most-important metabolic disease afflicting dairy cows early postpartum [2] It is usually characterized by increased plasma NEFA concentrations, accumulation of lipid. The high concentration of plasma NEFA in transition period cows contains a variety of fatty acids, with palmitic (PA), palmitoleic (POA), stearic (SA), oleic (OA), and linoleic (LA) acid being the most abundant [7,8,9]. These represent major fatty acid classes, saturated (SFA, PA, SA), monounsaturated (MUFA, POA, OA), and polyunsaturated (PUFA, LA). Some data from human studies indicate alterations in plasma long-chain fatty acid profiles among the healthy, non-alcoholic fatty liver and NASH [10], but it is unclear if the major fatty acids in the NEFA fraction of dairy cows have equal potency to induce hepatocytes lipid accumulation and injury

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