Oxylipin Data set

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 sEH
activity in the liver is modulated by high fat diets in male compared to
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 wildtype mice but gained less body weight on
higher fat diets. 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.