Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes

Mohammed Eslam, Alessandra Mangia, Thomas Berg, Henry Lik Yuen Chan, William L. Irving, Gregory J. Dore, Maria Lorena Abate, Elisabetta Bugianesi, Leon A. Adams, Mustafa A.M. Najim, Luca Miele, Martin Weltman, Lindsay Mollison, Wendy Cheng, Stephen Riordan, Janett Fischer, Manuel Romero‐Gomez, Ulrich Spengler, Jacob Nattermann, Antony Rahme, David Sheridan, David R. Booth, Duncan McLeod, Elizabeth Powell, Christopher Liddle, Mark W.

Carboxylesterase 2 prevents liver steatosis by modulating lipolysis, endoplasmic reticulum stress, and lipogenesis and is regulated by hepatocyte nuclear factor 4 alpha in mice

Yuanyuan Li, Munaf Zalzala, Kavita Jadhav, Yang Xu, Takhar Kasumov, Liya Yin, Yanqiao Zhang – 25 January 2016 – Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). So far, the underlying mechanism remains poorly understood. Here, we show that hepatic carboxylesterase 2 (CES2) is markedly reduced in NASH patients, diabetic db/db mice, and high‐fat diet (HFD)‐fed mice. Restoration of hepatic CES2 expression in db/db or HFD‐fed mice markedly ameliorates liver steatosis and insulin resistance.

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