Identification of crucial genetic factors, such as PPARγ, that regulate the pathogenesis of fatty liver disease in dairy cows is imperative for the sustainable development of dairy industry

Abstract

Fatty liver disease frequently occurs in dairy cows, a typical type of non-alcoholic fatty liver disease (NAFLD), resulting in a high culling rate of dairy cows during the perinatal period because of limitations of lactation and reproduction performance of cows with subsequent complications. This has been developing into a worldwide crucial industrial problem. Studies about NAFLD have shown that PPARγ (peroxisome proliferator-activated receptor γ) participates or regulates the fat deposition in liver by affecting the biological processes of hepatic lipid metabolism, insulin resistance, gluconeogenesis, oxidative stress, and inflammation, which all contribute to fatty liver. This review mainly focuses on the understanding of molecular pathogenesis of fatty liver disease in dairy cows by taking PPARγ as an example, so as to provide important information for discovering critical therapeutic targets, such as PPARγ, for fatty liver disease, and contribute to breeding improvement of fatty liver disease-resistant dairy cattle and eventually sustainable development of dairy industry. Frequently occurring fatty liver disease in dairy cows during the perinatal period, a typical type of non-alcoholic fatty liver disease (NAFLD), results in worldwide high culling rates of dairy cows (averagely about 25%) after calving. This has been developing into a critical industrial problem throughout the world, because the metabolic disease severely affects the welfare and economic value of dairy cows. Findings about the molecular mechanisms how the fatty liver disease develops would help scientists to discover novel therapeutic targets for NAFLD. Studies have shown that PPARγ participates or regulates the fat deposition in liver by affecting the biological processes of hepatic lipid metabolism, insulin resistance, gluconeogenesis, oxidative stress, endoplasmic reticulum stress and inflammation, which all contribute to fatty liver. This review mainly focuses on crucial regulatory mechanisms of PPARγ regulating lipid deposition in the liver via direct and/or indirect pathways, suggesting that PPARγ might be a potential critical therapeutic target for fatty liver disease, however, it would be of our significant interest to reveal the pathology and pathogenesis of NAFLD by using dairy cows with fatty liver as an animal model. This review will provide a molecular mechanism basis for understanding the pathogenesis of NAFLD.