2. Academic Validation
  3. Lipid overload impairs hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in large yellow croaker (Larimichthys crocea)

Lipid overload impairs hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in large yellow croaker (Larimichthys crocea)

  • Free Radic Biol Med. 2021 Aug 20;172:213-225. doi: 10.1016/j.freeradbiomed.2021.06.001.
Wei Fang 1,  Qiuchi Chen 1,  Kun Cui 1,  Qiang Chen 1,  Xueshan Li 1,  Ning Xu 1,  Kangsen Mai 2,  Qinghui Ai 3
Affiliations

Affiliations

  • 1 Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China.
  • 2 Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, 266237, Qingdao, Shandong, People's Republic of China.
  • 3 Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, 266237, Qingdao, Shandong, People's Republic of China. Electronic address: qhai@ouc.edu.cn.
PMID: 34116177 DOI: 10.1016/j.freeradbiomed.2021.06.001
Abstract

Lipid overload-induced hepatic steatosis is a major public health problem worldwide. However, the potential molecular mechanism is not completely understood. Herein, we found that high-fat diet (HFD) or oleic acid (OA) treatment induced oxidative stress which prevented the entry of hepatocyte nuclear factor 4 alpha (HNF4α) into the nucleus by activating protein kinase C delta (PKCδ) in vivo and in vitro in large yellow croaker (Larimichthys crocea). This reduced the level of microsomal triglyceride transfer protein (MTP) transcription, resulting in the impaired secretion of very-low-density lipoprotein (VLDL) and the abnormal accumulation of triglyceride (TG) in hepatocytes. Meanwhile, the detrimental effects induced by lipid overload could be partly alleviated by pretreating hepatocytes with Go6983 (PKCδ Inhibitor) or N-acetylcysteine (NAC, Reactive Oxygen Species (ROS) scavenger). In conclusion, for the first time, we revealed that lipid overload impaired hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in fish. This study may provide critical insights into potential intervention strategies against lipid overload-induced hepatic steatosis of fish and human beings.

Keywords

Hepatic steatosis; High-fat diet; Lipoprotein; Reactive oxygen species.

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