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KMID : 0620920230550081720
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Experimental & Molecular Medicine
2023 Volume.55 No. 8 p.1720 ~ p.1733
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Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy
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Chung Eu-Jin
Lee Yo-Han
Tam Dao
Jo Yun-Ju
Khim Keon-Woo
Eom Hye-Jin
Lee Ju-Eun
Song Yi-Jin
Choi Sun-Sil
Park Ki-Eun
Ji Ha-Neul
Chae Young-Chan
Myung Kyung-Jae
Kim Hong-Tae
Ryu Dong-Ryeol
Park Neung-Hwa
Park Sung-Ho
Choi Jang-Hyun
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Abstract
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Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment.
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KEYWORD
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Autophagy, Metabolic disorders
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