PMID- 34975481
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220225
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Soluble Epoxide Hydrolase Deletion Limits High-Fat Diet-Induced Inflammation.
PG  - 778470
LID - 10.3389/fphar.2021.778470 [doi]
LID - 778470
AB  - The soluble epoxide hydrolase (sEH) enzyme is a major regulator of bioactive 
      lipids. The enzyme is highly expressed in liver and kidney and modulates levels 
      of endogenous epoxy-fatty acids, which have pleiotropic biological effects 
      including limiting inflammation, neuroinflammation, and hypertension. It has been 
      hypothesized that inhibiting sEH has beneficial effects on limiting obesity and 
      metabolic disease as well. There is a body of literature published on these 
      effects, but typically only male subjects have been included. Here, we 
      investigate the role of sEH in both male and female mice and use a global sEH 
      knockout mouse model to compare the effects of diet and diet-induced obesity. The 
      results demonstrate that sEH activity in the liver is modulated by high-fat diets 
      more in male than in female mice. In addition, we characterized the sEH activity 
      in high fat content tissues and demonstrated the influence of diet on levels of 
      bioactive epoxy-fatty acids. The sEH KO animals had generally increased 
      epoxy-fatty acids compared to wild-type mice but gained less body weight on 
      higher-fat diets. Generally, proinflammatory prostaglandins and triglycerides 
      were also lower in livers of sEH KO mice fed HFD. Thus, sEH activity, 
      prostaglandins, and triglycerides increase in male mice on high-fat diet but are 
      all limited by sEH ablation. Additionally, these changes also occur in female 
      mice though at a different magnitude and are also improved by knockout of the sEH 
      enzyme.
CI  - Copyright (c) 2021 Wagner, Yang, Morisseau and Hammock.
FAU - Wagner, Karen M
AU  - Wagner KM
AD  - Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, 
      University of California Davis, Davis, CA, United States.
FAU - Yang, Jun
AU  - Yang J
AD  - Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, 
      University of California Davis, Davis, CA, United States.
FAU - Morisseau, Christophe
AU  - Morisseau C
AD  - Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, 
      University of California Davis, Davis, CA, United States.
FAU - Hammock, Bruce D
AU  - Hammock BD
AD  - Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, 
      University of California Davis, Davis, CA, United States.
LA  - eng
SI  - Dryad/10.5061/dryad.34tmpg4m4
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - R35 ES030443/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20211217
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8719166
OTO - NOTNLM
OT  - brown adipose tissue
OT  - eicosanoids
OT  - epoxy-fatty acids (EpFA)
OT  - omega-3
OT  - soluble epoxide hydrolase
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/01/04 06:00
MHDA- 2022/01/04 06:01
PMCR- 2021/12/17
CRDT- 2022/01/03 05:36
PHST- 2021/09/16 00:00 [received]
PHST- 2021/11/08 00:00 [accepted]
PHST- 2022/01/03 05:36 [entrez]
PHST- 2022/01/04 06:00 [pubmed]
PHST- 2022/01/04 06:01 [medline]
PHST- 2021/12/17 00:00 [pmc-release]
AID - 778470 [pii]
AID - 10.3389/fphar.2021.778470 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Dec 17;12:778470. doi: 10.3389/fphar.2021.778470. 
      eCollection 2021.