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Reply to Hansen: Essentiality of n-3 fatty acids

Open AccessPublished:April 26, 2019DOI:https://doi.org/10.1074/jbc.RL119.008526
      Professor Hansen makes an important point that arose from my imprecise use of the word “largely” in the sentence to which he refers (
      • Hansen H.S.
      Essentiality of n-6 fatty acids.
      ). Regrettably, I failed to note the significance of linoleic acid itself functioning in the maintenance of the water barrier in skin. In young rats, the scaly skin syndrome of omega-6 essential fatty acid (EFA) deficiency appears about 2 months after placing animals on EFA-deficient diets (
      • Burr G.O.
      • Burr M.M.
      On the nature and role of the fatty acids essential in nutrition.
      ). Hansen (
      • Hansen H.S.
      Essentiality of n-6 fatty acids.
      ) references the brilliant biochemical studies in this area by Brash and co-workers. A second feature of omega-6 EFA dietary deficiency is a failure to grow properly (
      • Lim H.
      • Paria B.C.
      • Das S.K.
      • Dinchuk J.E.
      • Langenbach R.
      • Trzaskos J.M.
      • Dey S.K.
      Multiple female reproductive failures in cyclooxygenase 2-deficient mice.
      ). This phenotype follows the onset of the scaly skin syndrome, that, as noted by Dr. Hansen, is partly due to dysfunction of the water barrier in skin.
      Other deleterious effects of omega-6 EFA deficiency noted in the early dietary studies involve dysfunctional renal development and problems with female reproduction (
      • Burr G.O.
      • Burr M.M.
      On the nature and role of the fatty acids essential in nutrition.
      ). Subsequent biochemical and genetic studies implicate defective prostaglandin (PG) formation as causal. Cyclooxygenase-2 (COX-2) knockout mice typically, although not uniformly, exhibit kidney abnormalities leading to early death. Multiple female reproductive problems of EFA dietary deficiency are associated with a lack of COX-2–mediated PG formation (
      • Lim H.
      • Paria B.C.
      • Das S.K.
      • Dinchuk J.E.
      • Langenbach R.
      • Trzaskos J.M.
      • Dey S.K.
      Multiple female reproductive failures in cyclooxygenase 2-deficient mice.
      ). An absence of COX-1–mediated PGF2α formation leads to failure of parturition (
      • Sugimoto Y.
      • Yamasaki A.
      • Segi E.
      • Tsuboi K.
      • Aze Y.
      • Nishimura T.
      • Oida H.
      • Yoshida N.
      • Tanaka T.
      • Katsuyama M.
      • Hasumoto K.
      • Murata T.
      • Hirata M.
      • Ushikubi F.
      • Negishi M.
      • Ichikawa A.
      • Narumiya S.
      Failure of parturition in mice lacking the prostaglandin F receptor.
      ,
      • Langenbach R.
      • Loftin C.D.
      • Lee C.
      • Tiano H.
      Cyclooxygenase-deficient mice: a summary of their characteristics and susceptibilities to inflammation and carcinogenesis.
      ). Early post-partum deaths observed in EFA deficiency are caused by the absence of COX-mediated PG formation required for closure of the ductus arteriosus (
      • Loftin C.D.
      • Trivedi D.B.
      • Tiano H.F.
      • Clark J.A.
      • Lee C.A.
      • Epstein J.A.
      • Morham S.G.
      • Breyer M.D.
      • Nguyen M.
      • Hawkins B.M.
      • Goulet J.L.
      • Smithies O.
      • Koller B.H.
      • Langenbach R.
      Failure of ductus arteriosus closure and remodeling in neonatal mice deficient in cyclooxygenase-1 and cyclooxygenase-2.
      ). Clearly, PGs formed primarily from 20-carbon omega-6 arachidonic acid via COXs are important mediators of life-sustaining biologic events.

      References

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        Multiple female reproductive failures in cyclooxygenase 2-deficient mice.
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        • Yamasaki A.
        • Segi E.
        • Tsuboi K.
        • Aze Y.
        • Nishimura T.
        • Oida H.
        • Yoshida N.
        • Tanaka T.
        • Katsuyama M.
        • Hasumoto K.
        • Murata T.
        • Hirata M.
        • Ushikubi F.
        • Negishi M.
        • Ichikawa A.
        • Narumiya S.
        Failure of parturition in mice lacking the prostaglandin F receptor.
        Science. 1997; 277 (9235889): 681-683
        • Langenbach R.
        • Loftin C.D.
        • Lee C.
        • Tiano H.
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        Ann. N.Y. Acad. Sci. 1999; 889 (10668482): 52-61
        • Loftin C.D.
        • Trivedi D.B.
        • Tiano H.F.
        • Clark J.A.
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        • Epstein J.A.
        • Morham S.G.
        • Breyer M.D.
        • Nguyen M.
        • Hawkins B.M.
        • Goulet J.L.
        • Smithies O.
        • Koller B.H.
        • Langenbach R.
        Failure of ductus arteriosus closure and remodeling in neonatal mice deficient in cyclooxygenase-1 and cyclooxygenase-2.
        Proc. Natl. Acad. Sci. U.S.A. 2001; 98 (11158594): 1059-1064