Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet

Yuwen Zhang, Qiang Li, Enyu Rao, Yanwen Sun, Michael E. Grossmann, Rebecca J Morris, Margot P Cleary, Bing Li

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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 ofE-FABP in obese mice decreased recruitment ofCD11c+ macrophages in skin tissues, reduced production of IL-1β and IL-18, and consequently dampened activation of effector Tcells. 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.

Original languageEnglish (US)
Pages (from-to)953-964
Number of pages12
JournalImmunity
Volume42
Issue number5
DOIs
StatePublished - May 19 2015

Bibliographical note

Funding Information:
The authors thank Dr. Jill Suttles for providing the E-FABP-deficient mice and Dr. Xuan-Mai T. Person and Dr. Michael D. Jensen for fat composition analysis with lipid mass spectrometry. This work was supported by the Hormel Foundation, Minnesota Obesity Center (5P30DK50456), Career Transition Fellowship (NMSS, TA3047-A-1), NIH R01 grants (CA18098601A1, CA17767901A1, CA157012), NIDDK (U24DK100469), and NCATs (UL1TR000135).

Publisher Copyright:
© 2015 Elsevier Inc..

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