The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and Epoxyeicosatrienoic Acids in Metabolic Diseases

Abstract

Metabolic diseases are associated with an increased risk of developing cardiovascular disease. The features comprising metabolic diseases include obesity, insulin resistance, hyperglycemia, hyperlipidemia, and hypertension. Recent evidence has emerged showcasing a role for cytochrome P450 epoxygenases, soluble epoxide hydrolase, and epoxyeicosatrienoic acids (EETs) in the development and progression of metabolic diseases. This review discusses the current knowledge related to the modulation of cytochrome P450 epoxygenases and soluble epoxide hydrolase to alter concentrations of biologically active EETs, resulting in effects on insulin resistance, lipid metabolism, obesity, and diabetes. Future areas of research to address current deficiencies in the understanding of these enzymes and their eicosanoid metabolites in various aspects of metabolic diseases are also discussed. Adv Nutr 2016;7:1122-8.

Blueberry and/or Banana Consumption Mitigate Arachidonic, Cytochrome P450 Oxylipin Generation During Recovery From 75-Km Cycling: A Randomized Trial

“…At least 57 human genes code for CYP enzymes, and expression is regulated by multiple factors including miRNAs, cytokines, hormones, and xenobiotics (35)(36)(37)(38). We are unaware of published data supporting a negative relationship between blood glucose and ARA-CYP oxylipin generation in response to carbohydrate feeding during intensive exercise.…”

Impact of a weight loss and fitness intervention on exercise‐associated plasma oxylipin patterns in obese, insulin‐resistant, sedentary women

“…Most convincingly, concentrations of 9,10‐DiHODE, 12,13‐DiHODE, and 9,10‐DiHOME were lower postintervention and displayed a statistically significant intervention effect. One hypothesis is that plasma diols reflect changes in sEH activities that associate with shifts in insulin sensitivity and metabolic health (see Xu et al, 2016). While a complete understanding of the role that sEH plays in glucose homeostasis has yet to emerge, sEH ablation increases pancreatic islet size and insulin signaling in high fat fed mice (Luria et al, 2011).…”

Soluble epoxide hydrolase as a therapeutic target for pain, inflammatory and neurodegenerative diseases

“…These fatty acid metabolites are implicated in critical biological processes throughout the body in most cells, tissues and organs (Funk, 2001; X. Xu, et al, 2016).…”