Hepatic autophagy and mitophagy status in dairy cows with subclinical and clinical ketosis.

Published on Feb 5, 2021in Journal of Dairy Science3.333
· DOI :10.3168/JDS.2020-19150
Taiyu Shen5
Estimated H-index: 5
(JLU: Jilin University),
Feng Xu1
Estimated H-index: 1
(JLU: Jilin University)
+ 14 AuthorsGuowen Liu27
Estimated H-index: 27
(JLU: Jilin University)
ABSTRACT Severe negative energy balance around parturition is an important contributor to ketosis, a metabolic disorder that occurs most frequently in the peripartal period. Autophagy and mitophagy are important processes responsible for breaking down useless or toxic cellular material, and in particular damaged mitochondria. However, the role of autophagy and mitophagy during the occurrence and development of ketosis is unclear. The objective of this study was to investigate autophagy and mitophagy in the livers of cows with subclinical ketosis (SCK) and clinical ketosis (CK). We assessed autophagy by measuring the protein abundance of microtubule-associated protein 1 light chain 3-II (LC3-II; encoded by MAP1LC3) and sequestosome-1 (p62, encoded by SQSTM1), as well as the mRNA abundance of autophagy-related genes 5 (ATG5), 7 (ATG7), and 12 (ATG12), beclin1 (BECN1), and phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3). Mitophagy was evaluated by measuring the protein abundance of the mitophagy upstream regulators PTEN-induced putative kinase 1 (PINK1) and Parkin. Liver and blood samples were collected from healthy cows [n = 15; blood β-hydroxybutyrate (BHB) concentration 3.0 mM with clinical signs) with similar lactation numbers (median = 3, range = 2 to 4) and days in milk (median = 6, range = 3 to 9). The serum activity of aspartate aminotransferase and alanine aminotransferase was greater in cows with CK than in healthy cows. Levels of oxidative stress biomarkers malondialdehyde and hydrogen peroxide were also higher in liver tissue from ketotic cows (SCK and CK) than from healthy cows. Compared with cows with CK and healthy cows, the hepatic mRNA abundance of MAP1LC3, SQSTM1, ATG5, ATG7, ATG12, and PIK3C3 was upregulated in cows with SCK. Compared with healthy cows, cows with SCK had a lower abundance of p62 and a greater abundance of LC3-II, but levels of both were higher in cows with CK. The mRNA abundance of ATG12 was lower in cows with CK than in healthy cows. Furthermore, the hepatic protein abundance of PINK1 and Parkin was greater in cows with SCK and slightly lower in cows with CK than in healthy cows. These data demonstrated differences in the hepatic activities of autophagy and mitophagy in cows with SCK compared with cows with CK. Although the precise mechanisms for these differences could not be discerned, autophagy and mitophagy seem to be involved in ketosis.
📖 Papers frequently viewed together
11 Citations
6 Citations
4 Citations
#1Xinwei Li (JLU: Jilin University)H-Index: 23
#2Zhen Shi (JLU: Jilin University)H-Index: 10
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 15 authors...
BACKGROUND AND PURPOSE: Identifying safe and effective compounds that target to mitophagy to eliminate impaired mitochondria may be an attractive therapeutic strategy for NAFLD. Here, we investigated the effects of cyanidin-3-O-glucoside (C3G) on NAFLD and the underlying mechanism. EXPERIMENTAL APPROACH: NAFLD was induced by a high-fat diet (HFD) for 16 weeks. C3G was administered during the last 4 weeks. In vivo, recombinant adenoviruses and AAV8 were used for overexpression and knockdown of PT...
6 CitationsSource
#1Hong Peng (SJTU: Shanghai Jiao Tong University)H-Index: 28
#2Fang Yang (SJTU: Shanghai Jiao Tong University)H-Index: 4
Last. Chuanxin Huang (SJTU: Shanghai Jiao Tong University)H-Index: 21
view all 7 authors...
ABSTRACTSQSTM1/p62 (sequestosome 1) is a critical macroautophagy/autophagy receptor that promotes the formation and degradation of ubiquitinated aggregates. SQSTM1 can be modified by ubiquitination...
12 CitationsSource
#1Hua Wang (Anhui Medical University)H-Index: 2
#1Hua Wang (Anhui Medical University)H-Index: 5
Last. Wen-Xing Ding (KU: University of Kansas)H-Index: 63
view all 12 authors...
Abstract Mitochondria damage plays a critical role in acetaminophen (APAP)-induced necrosis and liver injury. Cells can adapt and protect themselves by removing damaged mitochondria via mitophagy. PINK1-Parkin pathway is one of the major pathways that regulate mitophagy but its role in APAP-induced liver injury is still elusive. We investigated the role of PINK1-Parkin pathway in hepatocyte mitophagy in APAP-induced liver injury in mice. Wild-type (WT), PINK1 knockout (KO), Parkin KO, and PINK1 ...
29 CitationsSource
#1Yiwei Zhu (JLU: Jilin University)H-Index: 9
#2Guowen Liu (JLU: Jilin University)H-Index: 27
Last. Xinwei Li (JLU: Jilin University)H-Index: 23
view all 9 authors...
ABSTRACT Dairy cows with ketosis are characterized by high blood concentrations of ketone bodies and hepatic lipid metabolism disorder. The discrepancies in the abundance of mRNA encoding a variety of hepatic candidate genes in varying degrees of ketotic cows represent specific responses of the liver to the challenge of fatty acids and ketone bodies. Importantly, the expression disorder of hepatic genes involved in lipid metabolism plays a promoting role in the onset and progression of ketosis. ...
27 CitationsSource
#1Ning-Ping Zhang (Fudan University)H-Index: 2
#2Xue-Jing Liu (Fudan University)H-Index: 3
Last. Jian Wu (Fudan University)
view all 5 authors...
Activation of inflammation is an important mechanism in the development of nonalcoholic steatohepatitis (NASH). This study aims to delineate how mitophagy affects NLRP3 inflammasome activation in hepatic lipotoxicity. Mice were fed a high fat/calorie diet (HFCD) for 24 weeks. Primary rat hepatocytes were treated with palmitic acid (PA) for various periods of time. Mitophagy was measured by protein levels of LC3II and P62. NLRP3, caspase-1, interleukin (IL)-18, and IL-1β at mRNA and protein level...
32 CitationsSource
#1Tao Zhou (SJTU: Shanghai Jiao Tong University)H-Index: 5
#2Ling Chang (SHU: Shanghai University)H-Index: 1
Last. Jianjun Zhang (SJTU: Shanghai Jiao Tong University)H-Index: 42
view all 5 authors...
Abstract Obesity-related non-alcoholic fatty liver disease (NAFLD) is connected with mitochondrial stress and hepatocyte apoptosis. Parkin-related mitophagy sustains mitochondrial homeostasis and hepatocyte viability. However, the contribution and regulatory mechanisms of Parkin-related mitophagy in NAFLD are incompletely understood. Macrophage stimulating 1 (Mst1) is a novel mitophagy upstream regulator which excerbates heart and cancer apoptosisn via repressing mitophagy activity. The aim of o...
18 CitationsSource
#1Wenjun Xiong (Southern Medical University)H-Index: 2
#2Jinghai Hua (Southern Medical University)H-Index: 2
Last. Dingli Xu (Southern Medical University)H-Index: 19
view all 10 authors...
Abstract Background Mitochondrial quality control is crucial to the development of angiotensin II (AngII)-induced cardiac hypertrophy. PTEN induced putative kinase 1 (PINK1) is rapidly degraded in normal mitochondria but accumulates in damaged mitochondria, triggering autophagy to protect cells. PINK1 mediates mitophagy in general, but whether PINK1 mediates AngII-induced mitophagy and the effects of PINK1 on AngII-induced injury are unknown. This study was designed to investigate the function o...
18 CitationsSource
#1Bilon Khambu (IU: Indiana University)H-Index: 15
#2Shengmin Yan (IU: Indiana University)H-Index: 13
Last. Xiao Ming Yin (IU: Indiana University)H-Index: 75
view all 5 authors...
Abstract Autophagy is an evolutionarily conserved intracellular degradative function that is important for liver homeostasis. Accumulating evidence suggests that autophagy is deregulated during the progression and development of alcoholic and non-alcoholic liver diseases. Impaired autophagy prevents the clearance of excessive lipid droplets (LDs), damaged mitochondria, and toxic protein aggregates, which can be generated during the progression of various liver diseases, thus contributing to the ...
22 CitationsSource
#1Tianyi Wang (JLU: Jilin University)H-Index: 1
#2Conghe Liu (JLU: Jilin University)H-Index: 1
Last. Lili Jia (JLU: Jilin University)H-Index: 1
view all 3 authors...
Purpose Autophagy, as a highly conserved cellular degradation and recycling process, plays an important part in maintaining cellular homeostasis. PKC signaling is involved in multiple pathways including cell cycle progression, tumorigenesis, migration and autophagy.
6 CitationsSource
#1Xiliang Du (JLU: Jilin University)H-Index: 12
#2Yiwei Zhu (JLU: Jilin University)H-Index: 9
Last. Guowen Liu (JLU: Jilin University)H-Index: 27
view all 14 authors...
ABSTRACT The hepatic growth hormone (GH)–insulin-like growth factor (IGF)-I axis is essential for regulating intrahepatic lipid metabolism. Ketotic cows are characterized by high blood concentrations of fatty acids and β-hydroxybutyrate (BHB), which display lipotoxicity. The aim of this study was to investigate changes in the hepatic GH–IGF-I axis in ketotic cows and to determine the effects of fatty acids and BHB on the GH–IGF-I axis in calf hepatocytes. Liver and blood samples were collected f...
49 CitationsSource
Cited By0