Article
PNPLA3-I148M genetic variant rewires lipid metabolism to drive programmed cell death in human hepatocytes.
JCI insight - 8 Dec 2025
Florentino Rodrigo M, Animasahun Olamide, Haep Nils, Nenwani Minal, Omoloja Kehinde, Altay Leyla Nurcihan, Achreja Abhinav, Morita Kazutoyo, Motomura Takashi, Diaz-Aragon Ricardo, Faccioli Lanuza Ap, Sun Yiyue, Liu Zhenghao, Hu Zhiping, Yang Bo, Wuchu Fulei, Shankaran Ajay, Paserba Miya, Baratta Annalisa M, Arazov Shohrat, Kocas-Kilicarslan Zehra N, Meurs Noah, Behari Jaideep, Tafaleng Edgar N, Franks Jonathan, Ostrowska Alina, Tomiyama Takahiro, Yugawa Kyohei, Morinaga Akinari, Wang Zi, Takeishi Kazuki, Gavlock Dillon C, Miedel Mark, Taylor D Lansing, Fox Ira J, Yoshizumi Tomoharu, Nagrath Deepak, Soto-Gutierrez Alejandro
Abstract excerpt
Genetic variants in lipid metabolism influence the risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, and end-stage liver disease (ESLD). The mechanisms by which these variants drive disease are poorly understood. Because of the PNPLA3-I148M variant's strong correlation with all stages of the MASLD spectrum and the lack of tractable therapeutic targets, we sought to...
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