Hepatocyte-specific expression of human carboxylesterase 2 attenuates nonalcoholic steatohepatitis in mice

Abstract

Human CES2 attenuates high-fat/cholesterol/fructose diet-induced steatohepatitis and reverses steatohepatitis in db/db mice. Mechanistically, human CES2 induces lipolysis, fatty acid and glucose oxidation, and inhibits hepatic glucose production, inflammation, lipid oxidation, and apoptosis. Our data suggest that human CES2 may be targeted for treatment of non-alcoholic steatohepatitis (NASH).

Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease

“…Recently, bicyclol was reported to alleviate HFD-induced NAFLD through its anti-inflammatory mechanism ( Zhao et al, 2021 ). Our results showed that the expression of lipolysis-related protein CES2 was decreased in WD or WD/CCl 4 -induced mice, and bicyclol reversed CES2 expression to improve NAFLD, which is consistent with the fact that CES2 is reduced in high fat diet-induced obese mice, diabetic db/db mice, and NASH patients, while the liver disease was alleviated after CES2 was restored ( Li et al, 2016 ; Xu et al, 2021 ). Therefore, bicyclol might be contributory to its protective roles in NAFLD via restoring CES2.…”

Lipolysis: cellular mechanisms for lipid mobilization from fat stores

“…Adenoviral overexpression of human CES2 in the liver of mice prevents genetic-and diet-induced steatohepatitis by increasing TG hydrolase activity and FA oxidation and reduces SREBP1c mediated lipogenesis, inflammation, apoptosis and fibrosis. 259,260 .…”

CES2 sustains HNF4α expression to promote pancreatic adenocarcinoma progression through an epoxide hydrolase-dependent regulatory loop

“…Serine hydrolase carboxylesterase 2 (CES2) is a member of the alpha/beta fold hydrolase family [ 1 ] that is commonly overexpressed in various malignances [ [2] , [3] , [4] , [5] ] and plays a crucial role in the metabolism of endogenous esters, ester-containing drugs, and environmental toxicants [ 6 ]. The intrinsic role of CES2 in regulating lipid metabolism has been investigated in diabetes, liver steatosis, and nonalcoholic fatty liver disease [ [7] , [8] , [9] , [10] ]. To date, the relevance of CES2 in cancer has primarily been considered with respect to its functional role in mediating the activation of pro-drugs irinotecan and LY2334737 into their respective active forms [ 4 , 5 , [11] , [12] , [13] , [14] ], thereby providing a potential marker for predicting patient response to irinotecan- or LY2334737-containing regimens [ 2 , 5 , 15 , 16 ].…”