Epidermal Fatty Acid binding protein promotes skin inflammation induced by high-fat diet

Immunity. 2015 May 19;42(5):953-964. doi: 10.1016/j.immuni.2015.04.016.


Defining specific cellular and molecular mechanisms in most obesity-related diseases remains an important challenge. Here we report a serendipitous finding that consumption of a high-fat diet (HFD) greatly increased the occurrence of skin lesions in C57BL/6 mice. We demonstrated that HFD induced the accumulation of a specific type of CD11c(+) macrophages in skin preceding detectable lesions. These cells primed skin to induce IL-1β and IL-18 signaling, which further promoted the cytokines IFN-γ- and IL-17-mediated skin inflammation. Mechanistically, epidermal fatty acid binding protein (E-FABP) was significantly upregulated in skin of obese mice, which coupled lipid droplet formation and NLRP3 inflammasome activation. Deficiency of E-FABP in obese mice decreased recruitment of CD11c(+) macrophages in skin tissues, reduced production of IL-1β and IL-18, and consequently dampened activation of effector T cells. Furthermore, E-FABP-deficient mice are completely resistant to HFD-induced skin lesions. Collectively, E-FABP represents a molecular sensor triggering HFD-induced skin inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects*
  • Fatty Acid-Binding Proteins / deficiency
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / immunology
  • Fatty Acid-Binding Proteins / metabolism*
  • Immunohistochemistry
  • Inflammation / etiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Proteins / deficiency
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Skin Diseases / genetics
  • Skin Diseases / immunology*
  • T-Lymphocytes / immunology


  • Cytokines
  • Fabp5 protein, mouse
  • Fatty Acid-Binding Proteins
  • Neoplasm Proteins