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Proc Natl Acad Sci U S A. 2018 May 15;115(20):5283-5288. doi: 10.1073/pnas.1721711115. Epub 2018 May 1.

Lipidomic profiling reveals soluble epoxide hydrolase as a therapeutic target of obesity-induced colonic inflammation.

Author information

1
Department of Food Science, University of Massachusetts, Amherst, MA 01003.
2
Department of Entomology and Nematology, University of California, Davis, CA 95616.
3
Comprehensive Cancer Center, University of California, Davis, CA 95616.
4
College of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China.
5
Department of Mathematics and Statistics, University of Massachusetts, Amherst, MA 01003.
6
State Forestry Administration Key Open Laboratory, International Center for Bamboo and Rattan, Beijing 100102, China.
7
Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA 01003.
8
Center for Nephrology and Metabolomics and Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 210072, China.
9
Nutrition and Cancer Prevention Laboratory, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003.
10
Department of Entomology and Nematology, University of California, Davis, CA 95616; bdhammock@ucdavis.edu guodongzhang@umass.edu.
11
Department of Food Science, University of Massachusetts, Amherst, MA 01003; bdhammock@ucdavis.edu guodongzhang@umass.edu.

Abstract

Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. Considering the obesity epidemic in Western countries, it is important to identify novel therapeutic targets for obesity-induced colonic inflammation, to develop targeted strategies for prevention. Eicosanoids are endogenous lipid signaling molecules involved in regulating inflammation and immune responses. Using an LC-MS/MS-based lipidomics approach, we find that obesity-induced colonic inflammation is associated with increased expression of soluble epoxide hydrolase (sEH) and its eicosanoid metabolites, termed fatty acid diols, in colon tissue. Furthermore, we find that pharmacological inhibition or genetic ablation of sEH reduces colonic concentrations of fatty acid diols, attenuates obesity-induced colonic inflammation, and decreases obesity-induced activation of Wnt signaling in mice. Together, these results support that sEH could be a novel therapeutic target for obesity-induced colonic inflammation and associated diseases.

KEYWORDS:

colonic inflammation; obesity; soluble epoxide hydrolase

PMID:
29717038
PMCID:
PMC5960306
DOI:
10.1073/pnas.1721711115
[Indexed for MEDLINE]
Free PMC Article

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