Impaired hepatic autophagic activity in dairy cows with severe fatty liver is associated with inflammation and reduced liver function

Xiliang Du, Guowen Liu, Juan J. Loor, Zhiyuan Fang, Ryan Bucktrout, Yuchen Yang, Qianqian Ye, Zhen Shi, Taiyu Shen, Xinghui Wang, Zhicheng Peng, Chenxu Zhao, Bin Lv, Dongmei Xing, Yiwei Zhu, Xiaobing Li, Xinwei Li

Research output: Contribution to journalArticle

Abstract

The ability of liver to respond to changes in nutrient availability is essential for the maintenance of metabolic homeostasis. Autophagy encompasses mechanisms of cell survival, including capturing, degrading, and recycling of intracellular proteins and organelles in lysosomes. During negative nutrient status, autophagy provides substrates to sustain cellular metabolism and hence, tissue function. Severe negative energy balance in dairy cows is associated with fatty liver. The aim of this study was to investigate the hepatic autophagy status in dairy cows with severe fatty liver and to determine associations with biomarkers of liver function and inflammation. Liver and blood samples were collected from multiparous cows diagnosed as clinically healthy (n = 15) or with severe fatty liver (n = 15) at 3 to 9 d in milk. Liver tissue was biopsied by needle puncture, and serum samples were collected on 3 consecutive days via jugular venipuncture. Concentrations of free fatty acids and β-hydroxybutyrate were greater in cows with severe fatty liver. Milk production, dry matter intake, and concentration of glucose were all lower in cows with severe fatty liver. Activities of serum aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, and γ-glutamyl transferase were all greater in cows with severe fatty liver. Serum concentrations of haptoglobin and serum amyloid A were also markedly greater in cows with severe fatty liver. The mRNA expression of autophagosome formation-related gene ULK1 was lower in the liver of dairy cows with severe fatty liver. However, the expression of other autophagosome formation-related genes, beclin 1 (BECN1), phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), autophagy-related gene (ATG) 3, ATG5, and ATG12, did not differ. More important, ubiquitinated proteins, protein expression of sequestosome-1 (SQSTM1, also called p62), and microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3)-II was greater in cows with severe fatty liver. Transmission electron microscopy revealed an increased number of autophagosomes in the liver of dairy cows with severe fatty liver. Taken together, these results indicate that excessive lipid infiltration of the liver impairs autophagic activity that may lead to cellular damage and inflammation.

Original languageEnglish (US)
Pages (from-to)11175-11185
Number of pages11
JournalJournal of Dairy Science
Volume101
Issue number12
DOIs
StatePublished - Dec 2018

Keywords

  • autophagy
  • inflammation
  • lactation
  • liver lipidosis

ASJC Scopus subject areas

  • Food Science
  • Animal Science and Zoology
  • Genetics

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  • Cite this

    Du, X., Liu, G., Loor, J. J., Fang, Z., Bucktrout, R., Yang, Y., Ye, Q., Shi, Z., Shen, T., Wang, X., Peng, Z., Zhao, C., Lv, B., Xing, D., Zhu, Y., Li, X., & Li, X. (2018). Impaired hepatic autophagic activity in dairy cows with severe fatty liver is associated with inflammation and reduced liver function. Journal of Dairy Science, 101(12), 11175-11185. https://doi.org/10.3168/jds.2018-15120