Journal
CELL REPORTS
Volume 18, Issue 3, Pages 636-646Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.12.070
Keywords
-
Categories
Funding
- O.E. och Edla Johanssons vetenskapliga stiftelse
- NovoNordisk Foundation
- Stockholm County Council [ALF]
- (Swedish Research Council)
- Strategic Diabetes Program at Karolinska Institutet [2009-1068]
- European Research Council Ideas Program
- Swedish Research Council [2011-3550, 2015-00165]
- Swedish Diabetes Foundation [DIA2012-082, DIA2015-032]
- Swedish Foundation for Strategic Research [SRL10-0027]
- Diabetes Wellness Network Sweden [783_2015PG]
- NovoNordisk Foundation [NNF14OC0009941]
- Stockholm County Council [20120086, 20150326]
- Swedish Society for Medical Research
- Novo Nordisk Fonden [NNF14OC0010883, NNF15OC0016536, NNF14OC0009941, NNF13OC0005961, NNF12OC1016062] Funding Source: researchfish
Ask authors/readers for more resources
Serine hydrolases are a large family of multifunctional enzymes known to influence obesity. Here, we performed activity-based protein profiling to assess the functional level of serine hydrolases in liver biopsies from lean and obese humans in order to gain mechanistic insight into the pathophysiology of metabolic disease. We identified reduced hepatic activity of carboxylesterase 2 (CES2) and arylacetamide deacetylase (AADAC) in human obesity. In primary human hepatocytes, CES2 knockdown impaired glucose storage and lipid oxidation. In mice, obesity reduced CES2, whereas adenoviral delivery of human CES2 reversed hepatic steatosis, improved glucose tolerance, and decreased inflammation. Lipidomic analysis identified a network of CES2-regulated lipids altered in human and mouse obesity. CES2 possesses triglyceride and diacylglycerol lipase activities and displayed an inverse correlation with HOMA-IR and hepatic diacylglycerol concentrations in humans. Thus, decreased CES2 is a conserved feature of obesity and plays a causative role in the pathogenesis of obesity-related metabolic disturbances.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available