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

Abstract

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.

• Authors: Yuwen Zhang, Qiang Li, Enyu Rao, Yanwen Sun, Michael E Grossmann, Rebecca J Morris, Margot P Cleary, Bing Li
• Journal: Immunity (Immunity) Vol. 42 Issue 5 Pg. 953-964 (May 19 2015) ISSN: 1097-4180 [Electronic] United States
• PMID: 25992864 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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