Metabolic impact of sEH uncovered
In a recent study, directed by Pr Jeremy Bellien, the physiological role of the phosphatase domain of the bi-valent enzyme soluble epoxide hydrolase (sEH) was investigated. See M. Leuillier et al . Journal of Advanced Research 2022 https://doi.org/10.1016/j.jare.2022.03.004
Briefly, selective inactivation of the phosphatase domain of sEH was produced using a cre-lox KI strategy in rats,. This led to metabolic alterations, including decreased lysophosphatidic acid metabolism. In the setting of a high fat diet, lack of the phosphatase domain of sEH impacted both body weight gain and insulin sensitivity, which was improved as compared to wildtype animals that developed obesity and insulin resistance. The underlying mechanism involved increased energy expenditure by stimulation of brown adipose tissue thermogenesis. Further, KI rats exhibited enhanced basal cardiac mitochondrial activity and left ventricular contractility, and animals were protected against cardiac ischemia –reperfusion injury.
This new study reveals that the phosphatase domain of sEH is a key player in energy and fat metabolism, which together with the hydrolase domain of sEH contributes to the regulation of cardiometabolic homeostasis.