Abstract
The soluble epoxide hydrolase (sEH) is a regulatory enzyme responsible for the metabolism of bioactive lipid epoxides of both omega-6 and omega-3 long chain polyunsaturated fatty acids. These natural epoxides mediate cell signaling in several physiological functions including blocking inflammation, high blood pressure and both inflammatory and neuropathic pain. Inhibition of the sEH maintains the level of endogenous bioactive epoxy-fatty acids (EpFA) and allows them to exert their generally beneficial effects. The Akita (Ins2Akita or Ins2C96Y) mice represent a maturity-onset of diabetes of the young (MODY) model in lean, functionally unimpaired animals, with a sexually dimorphic disease phenotype. This allowed for a test of male and female mice in a battery of functional and nociceptive assays to probe the role of sEH in this system. The results demonstrate that inhibiting the sEH is analgesic in diabetic neuropathy and this occurs in a sexually dimorphic manner. Interestingly, sEH activity is also sexually dimorphic in the Akita model, and moreover correlates with disease status particularly in the hearts of male mice. In addition, in vivo levels of oxidized lipid metabolites also correlate with increased sEH expression and the pathogenesis of disease in this model. Thus, sEH is a target to effectively block diabetic neuropathic pain but also demonstrates a potential role in mitigating the progression of this disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 69-76 |
| Number of pages | 8 |
| Journal | Behavioural Brain Research |
| Volume | 326 |
| DOIs | |
| State | Published - May 30 2017 |
Fingerprint
Keywords
- Anti-nociception
- Chronic pain
- Diabetic neuropathy
- Epoxy-fatty acid (EpFA)
- Soluble epoxide hydrolase (sEH)
ASJC Scopus subject areas
- Behavioral Neuroscience
Cite this
Soluble epoxide hydrolase inhibition alleviates neuropathy in Akita (Ins2 Akita) mice. / Wagner, Karen; Gilda, Jennifer; Yang, Jun; Wan, Debin; Morisseau, Christophe; Gomes, Aldrin V; Hammock, Bruce D.
In: Behavioural Brain Research, Vol. 326, 30.05.2017, p. 69-76.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Soluble epoxide hydrolase inhibition alleviates neuropathy in Akita (Ins2 Akita) mice
AU - Wagner, Karen
AU - Gilda, Jennifer
AU - Yang, Jun
AU - Wan, Debin
AU - Morisseau, Christophe
AU - Gomes, Aldrin V
AU - Hammock, Bruce D.
PY - 2017/5/30
Y1 - 2017/5/30
N2 - The soluble epoxide hydrolase (sEH) is a regulatory enzyme responsible for the metabolism of bioactive lipid epoxides of both omega-6 and omega-3 long chain polyunsaturated fatty acids. These natural epoxides mediate cell signaling in several physiological functions including blocking inflammation, high blood pressure and both inflammatory and neuropathic pain. Inhibition of the sEH maintains the level of endogenous bioactive epoxy-fatty acids (EpFA) and allows them to exert their generally beneficial effects. The Akita (Ins2Akita or Ins2C96Y) mice represent a maturity-onset of diabetes of the young (MODY) model in lean, functionally unimpaired animals, with a sexually dimorphic disease phenotype. This allowed for a test of male and female mice in a battery of functional and nociceptive assays to probe the role of sEH in this system. The results demonstrate that inhibiting the sEH is analgesic in diabetic neuropathy and this occurs in a sexually dimorphic manner. Interestingly, sEH activity is also sexually dimorphic in the Akita model, and moreover correlates with disease status particularly in the hearts of male mice. In addition, in vivo levels of oxidized lipid metabolites also correlate with increased sEH expression and the pathogenesis of disease in this model. Thus, sEH is a target to effectively block diabetic neuropathic pain but also demonstrates a potential role in mitigating the progression of this disease.
AB - The soluble epoxide hydrolase (sEH) is a regulatory enzyme responsible for the metabolism of bioactive lipid epoxides of both omega-6 and omega-3 long chain polyunsaturated fatty acids. These natural epoxides mediate cell signaling in several physiological functions including blocking inflammation, high blood pressure and both inflammatory and neuropathic pain. Inhibition of the sEH maintains the level of endogenous bioactive epoxy-fatty acids (EpFA) and allows them to exert their generally beneficial effects. The Akita (Ins2Akita or Ins2C96Y) mice represent a maturity-onset of diabetes of the young (MODY) model in lean, functionally unimpaired animals, with a sexually dimorphic disease phenotype. This allowed for a test of male and female mice in a battery of functional and nociceptive assays to probe the role of sEH in this system. The results demonstrate that inhibiting the sEH is analgesic in diabetic neuropathy and this occurs in a sexually dimorphic manner. Interestingly, sEH activity is also sexually dimorphic in the Akita model, and moreover correlates with disease status particularly in the hearts of male mice. In addition, in vivo levels of oxidized lipid metabolites also correlate with increased sEH expression and the pathogenesis of disease in this model. Thus, sEH is a target to effectively block diabetic neuropathic pain but also demonstrates a potential role in mitigating the progression of this disease.
KW - Anti-nociception
KW - Chronic pain
KW - Diabetic neuropathy
KW - Epoxy-fatty acid (EpFA)
KW - Soluble epoxide hydrolase (sEH)
UR - http://www.scopus.com/inward/record.url?scp=85014820250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014820250&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2017.02.048
DO - 10.1016/j.bbr.2017.02.048
M3 - Article
C2 - 28259677
AN - SCOPUS:85014820250
VL - 326
SP - 69
EP - 76
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
ER -