PMID- 28863368 OWN - NLM STAT- MEDLINE DCOM- 20180502 LR - 20190122 IS - 1873-4847 (Electronic) IS - 0955-2863 (Print) IS - 0955-2863 (Linking) VI - 49 DP - 2017 Nov TI - Postprandial effect to decrease soluble epoxide hydrolase activity: roles of insulin and gut microbiota. PG - 8-14 LID - S0955-2863(17)30340-6 [pii] LID - 10.1016/j.jnutbio.2017.07.006 [doi] AB - Epoxides of free fatty acids (FFAs), especially epoxyeicosatrienoic acids (EETs), are lipid mediators with beneficial effects in metabolic and cardiovascular (CV) health. FFA epoxides are quickly metabolized to biologically less active diols by soluble epoxide hydrolase (sEH). Inhibition of sEH, which increases EET levels, improves glucose homeostasis and CV health and is proposed as an effective strategy for the treatment of diabetes and CV diseases. Here, we show evidence that sEH activity is profoundly reduced in postprandial states in rats; plasma levels of 17 sEH products (i.e., FFA diols), detected by targeted oxylipin analysis, all decreased after a meal. In addition, the ratios of sEH product to substrate (sEH P/S ratios), which may reflect sEH activity, decreased ~70% on average 2.5 h after a meal in rats (P<.01). To examine whether this effect was mediated by insulin action, a hyperinsulinemic-euglycemic clamp was performed for 2.5 h, and sEH P/S ratios were assessed before and after the clamp. The clamp resulted in small increases rather than decreases in sEH P/S ratios (P<.05), indicating that insulin cannot account for the postprandial decrease in sEH P/S ratios. Interestingly, in rats treated with antibiotics to deplete gut bacteria, the postprandial effect to decrease sEH P/S ratios was completely abolished, suggesting that a gut bacteria-derived factor(s) may be responsible for the effect. Further studies are warranted to identify such a factor(s) and elucidate the mechanism by which sEH activity (or sEH P/S ratio) is reduced in postprandial states. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Yang, Jun AU - Yang J AD - Department of Entomology and Nematology, University of California, Davis, CA, USA. FAU - Oh, Young Taek AU - Oh YT AD - Department of Physiology and Biophysics, Keck School of Medicine of USC, Los Angeles, CA, USA. FAU - Wan, Debin AU - Wan D AD - Department of Entomology and Nematology, University of California, Davis, CA, USA. FAU - Watanabe, Richard M AU - Watanabe RM AD - Department of Physiology and Biophysics, Keck School of Medicine of USC, Los Angeles, CA, USA; Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA. FAU - Hammock, Bruce D AU - Hammock BD AD - Department of Entomology and Nematology, University of California, Davis, CA, USA. FAU - Youn, Jang H AU - Youn JH AD - Department of Physiology and Biophysics, Keck School of Medicine of USC, Los Angeles, CA, USA. Electronic address: youn@usc.edu. LA - eng GR - P42 ES004699/ES/NIEHS NIH HHS/United States GR - R01 ES002710/ES/NIEHS NIH HHS/United States GR - U24 DK097154/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20170721 PL - United States TA - J Nutr Biochem JT - The Journal of nutritional biochemistry JID - 9010081 RN - 0 (Anti-Bacterial Agents) RN - 0 (Biomarkers) RN - 0 (Eicosanoids) RN - 0 (Insulin) RN - 0 (Oxylipins) RN - 0 (Potassium, Dietary) RN - EC 3.3.2.- (Epoxide Hydrolases) RN - EC 3.3.2.10 (EPHX2 protein, rat) SB - IM MH - Algorithms MH - Animals MH - Anti-Bacterial Agents/pharmacology MH - Biomarkers/blood MH - Cardiovascular Diseases/blood/metabolism/prevention & control MH - Eicosanoids/blood/metabolism MH - Epoxide Hydrolases/*blood/chemistry/metabolism MH - Gastrointestinal Microbiome/drug effects/*physiology MH - Glucose Clamp Technique MH - Insulin/analysis/*metabolism MH - Insulin Secretion MH - Male MH - *Meals MH - *Models, Biological MH - *Oxidative Stress/drug effects MH - Oxylipins/blood MH - Postprandial Period MH - Potassium, Dietary/*administration & dosage/therapeutic use MH - Rats, Wistar MH - Reproducibility of Results MH - Solubility PMC - PMC5858941 MID - NIHMS944350 OTO - NOTNLM OT - Cardiovascular disease OT - Diabetes OT - Dietary potassium OT - FFA epoxides OT - Oxylipin analysis COIS- Disclosure statement: We have no conflicts of interest to disclose in connection with the manuscript. EDAT- 2017/09/02 06:00 MHDA- 2018/05/03 06:00 PMCR- 2018/11/01 CRDT- 2017/09/02 06:00 PHST- 2017/04/18 00:00 [received] PHST- 2017/06/20 00:00 [revised] PHST- 2017/07/18 00:00 [accepted] PHST- 2017/09/02 06:00 [pubmed] PHST- 2018/05/03 06:00 [medline] PHST- 2017/09/02 06:00 [entrez] PHST- 2018/11/01 00:00 [pmc-release] AID - S0955-2863(17)30340-6 [pii] AID - 10.1016/j.jnutbio.2017.07.006 [doi] PST - ppublish SO - J Nutr Biochem. 2017 Nov;49:8-14. doi: 10.1016/j.jnutbio.2017.07.006. Epub 2017 Jul 21.