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  • Diet-induced obesity promotes infection by impairment of the innate antimicrobial defense function of dermal adipocyte progenitors
Title: Diet-induced obesity promotes infection by impairment of the innate antimicrobial defense function of dermal adipocyte progenitors
Infections are a major complication of obesity, but the mechanisms responsible for impaired defense against microbes are not well understood. Here, we found that adipocyte progenitors were lost from the dermis during diet-induced obesity (DIO) in humans and mice. The loss of adipogenic fibroblasts from mice resulted in less antimicrobial peptide production and greatly increased susceptibility to Staphylococcus aureus infection. The decrease in adipocyte progenitors in DIO mice was explained by expression of transforming growth factor–β (TGFβ) by mature adipocytes that then inhibited adipocyte progenitors and the production of cathelicidin in vitro. Administration of a TGFβ receptor inhibitor or a peroxisome proliferator–activated receptor–γ agonist reversed this inhibition in both cultured adipocyte progenitors and in mice and subsequently restored the capacity of obese mice to defend against S. aureus skin infection. Together, these results explain how obesity promotes dysfunction of the antimicrobial function of reactive dermal adipogenesis and identifies potential therapeutic targets to manage skin infection associated with obesity.  more » « less
Award ID(s):
1763272
PAR ID:
10222838
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Science Translational Medicine
Volume:
13
Issue:
577
ISSN:
1946-6234
Page Range / eLocation ID:
eabb5280
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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