Deficiency of n-6 polyunsaturated fatty acids is mainly responsible for atopic dermatitis-like pruritic skin inflammation in special diet-fed hairless mice

Exp Dermatol. 2013 Apr;22(4):272-7. doi: 10.1111/exd.12120.


Hairless mice fed a special diet, HR-AD, develop atopic dermatitis (AD)-like skin inflammation with skin barrier defects and itch-related scratching; however, the ingredient(s) causing the dermatitis remains unclear. In this study, we examined whether deficiency of certain polyunsaturated fatty acids (PUFAs) is involved in HR-AD-induced AD. High-purity PUFAs were given to HR-AD-fed mice by dietary supplementation or gavage. Fatty acid levels in the serum and skin were determined by using gas chromatography-mass spectrometry. In serum from HR-AD-fed mice, linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3), as well as their metabolites, were markedly decreased. When mice were fed HR-AD supplemented with LA or ALA in an amount equal to that contained in a normal diet, the development of AD-like symptoms was completely prevented by supplementation with LA but not with ALA. Relatively high dose of ALA slightly alleviated skin barrier defects, but did neither itch-related scratching nor skin inflammation. On the other hand, gavage administration of LA metabolites, such as γ-linolenic acid and arachidonic acid (AA), significantly ameliorated established dermatitis without increasing LA in the serum and skin. Moreover, AA-induced amelioration of dermatitis was not affected by pharmacological blockade of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX), suggesting no involvement of 5-LOX- or COX-mediated AA metabolites in the amelioration. In conclusion, our results indicate that deficiency of n-6 PUFAs is mainly responsible for AD-like symptoms by HR-AD feeding. Thus, this model could be useful for studying the pathomechanisms associated with deficiency of n-6 PUFAs in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / administration & dosage
  • Dermatitis, Atopic / diet therapy
  • Dermatitis, Atopic / etiology*
  • Dermatitis, Atopic / metabolism
  • Diet / adverse effects
  • Dietary Fats, Unsaturated / administration & dosage
  • Disease Models, Animal
  • Fatty Acids / blood
  • Fatty Acids / metabolism
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Omega-6 / blood
  • Fatty Acids, Omega-6 / deficiency*
  • Fatty Acids, Omega-6 / metabolism
  • Female
  • Linoleic Acid / administration & dosage
  • Linoleic Acid / metabolism
  • Mice
  • Mice, Hairless
  • Pruritus / etiology
  • Pruritus / metabolism
  • Pruritus / pathology
  • Skin / metabolism
  • Skin / pathology


  • Dietary Fats, Unsaturated
  • Fatty Acids
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Arachidonic Acid
  • Linoleic Acid