Journal
CELL DEATH & DISEASE
Volume 12, Issue 3, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-021-03536-8
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Funding
- Ministry of Science and Technology of China [2016YFA0101100]
- National Natural Science Foundation of China [91949201, 81830014, :81570348]
- Wuhan Science and Technology Plan Project [2018060401011328]
- Natural Science Foundation of Hubei Province [2020CFB429]
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Nonalcoholic fatty liver disease (NAFLD) is a common clinical disease without approved drugs due to unclear pathological mechanisms. The newly discovered oncogene WBP2 has been found to decrease in NAFLD and its overexpression can alleviate liver fat deposition and insulin resistance, while knockdown aggravates these symptoms. This suggests a potential new direction for future research on NAFLD.
Nonalcoholic fatty liver disease (NAFLD) is prevalent clinically and can lead to more serious chronic liver disease. However, the pathological mechanism is still unclear, and thus, there are no approved drugs on the market. Transcriptional coactivator WW domain-binding protein 2 (WBP2) is a newly discovered oncogene that has an important relationship with the occurrence and development of breast cancer and mediates the interaction between Wnt and various other signaling pathways. The expression level of WBP2 was decreased in NAFLD. Overexpression of WBP2 with AAV in vivo alleviated liver fat deposition and insulin resistance induced by a high-fat diet (HFD). Knockdown of WBP2 with AAV aggravated HFD-induced fatty liver and insulin resistance. In vitro experiments showed that in the human normal hepatocyte cell line LO2 and primary hepatocytes isolated from mice, overexpression of WBP2 reduced fat deposition, and knocking out or knocking down WBP2 aggravated PA-induced fat deposition. Through mass spectrometry, we found that WBP2 can bind to AMPK beta 1, and by mutating AMPK beta 1, we found that WBP2 can induce phosphorylation of AMPK beta 1 at S108 and then activate the AMPK pathway to affect lipid metabolism. The effect of WBP2 on NAFLD provides a possible new direction for future research on NAFLD.
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