(±)12(13)-DiHOME

(±)12(13)-DiHOME is the diol form of (±)12(13)-EpOME , a cytochrome P450-derived epoxide of linoleic acid also known as isoleukotoxin. [1]  It is formed from 12(13)-EpOME by soluble epoxide hydrolase (sEH) in neutrophils. [2] 12(13)-DiHOME is toxic to Sf21 cells expressing sEH and to lacZ-expressing control cells, unlike isoleukotoxin, which is only toxic to cells containing sEH.[1] [2] Levels of 12(13)-DiHOME are increased in rat spinal cord following burn injury, and it enhances cold tolerance, increases fatty acid uptake into brown adipocytes, and decreases serum triglyceride levels in mice. Levels are also elevated in bronchoalveolar lavage fluid (BALF) in humans following exposure to biodiesel exhaust and in exhaled breath condensate in patients with allergic asthma following allergen exposure.[5] [6] Plasma levels of 12(13)-DiHOME are increased immediately following moderate-intensity exercise in mice and humans, an effect that can be prevented by brown adipose tissue removal in the mouse.[7]

Reference:
[1]. Greene, J.F., Williamson, K.C., Newman, J.W., et al. Metabolism of monoepoxides of methyl linoleate: Bioactivation and detoxification. Arch. Biochem. Biophys. 376(2), 420-432 (2000).
[2]. Moghaddam, M.F., Grant, D.F., Cheek, J.M., et al. Bioactivation of leukotoxins to their toxic diols by epoxide hydrolase. Nat. Med. 3(5), 562-566 (1997).
[3]. Green, D.P., Ruparel, S., Gao, X., et al. Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury. Mol. Pain 12, (2016).
[4]. Lynes, M.D., Leiria, L.O., Lundh, M., et al. The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat. Med. 23(5), 631-637 (2017).
[5]. Gouveia-Figueira, S., Karimpour, M., Bosson, J.A., et al. Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure. Anal. Bioanal. Chem. 409(11), 2967-2980 (2017).
[6]. Nording, M.L., Yang, J., Hegedus, C.M., et al. Endogenous levels of five fatty acid metabolites in exhaled breath condensate to monitor asthma by high-performance liquid chromatography: Electrospray tandem mass spectrometry. IEEE Sens. J. 10(1), 123-130 (2010).
[7]. Stanford, K.I., Lynes, M.D., Takahashi, H., et al. 12,13-diHOME: An exercise-induced lipokine that increases skeletal muscle fatty acid uptake. Cell Metab. 27(5), 1111-1120 (2018).