Omega-3 fatty acid metabolism in controlling inflammation and related diseases

Prof. Makoto Arita  makoto.arita@riken.jp

 

Omega-3 polyunsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are widely held to have beneficial effects in many inflammatory diseases. Also, elevation in tissue levels of omega-3 PUFAs in fatty acid n-3 desaturase (fat-1) transgenic mice exhibits resistance to inflammatory disease models. To elucidate the molecular mechanisms underlying the beneficial effects of omega-3 PUFAs, we developed a comprehensive LC-MS/MS-based lipidomic system that can detect and quantify more than 500 of fatty acid metabolites simultaneously. Using a genetic model, namely fat-1 transgenic mice, we examined the biological impact and lipid metabolome changes with enhanced omega-3/omega-6 fatty acid ratio at tissue and cellular levels. Also we demonstrated LC-MS/MS-based lipidomic analyses, and identified several unique omega-3 fatty acid metabolites with potent biological activities in vivo. These metabolites may underlie some of the beneficial actions of omega-3 PUFAs in controlling inflammation and related diseases.

 

References

  • Kunisawa J, Arita M, Hayasaka T, Harada T, Iwamoto R, Nagasawa R, Shikata S, Nagatake T, Suzuki H, Hashimoto E, Kurashima Y, Suzuki Y, Arai H, Setou M, Kiyono H. Dietary ω3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicostetraenoic acid in the gut. Sci Rep 5, 9750 (2015)
  • Endo J, Sano M, Isobe Y, Fukuda K, Kang JX, Arai H, Arita M. 18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload-induced maladaptive cardiac remodeling. J Exp Med 211, 1673-1687 (2014)