期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 13, 期 577, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.abb5280
关键词
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资金
- Chinese NSFC grants [81971551, K2918001]
- Xiamen University grant [X2123303]
- NIH [R01-AR067273, R01-AR069653, P30-AR075047, R01 AR076082, R37 AI052453, U19 AI117673]
- Pew Charitable Trust
- LEO Foundation Award
- NSF [DMS1763272]
- Simons Foundation [594598]
- UC Irvine Chancellor's ADVANCE Postdoctoral Fellowship Program
- NSF-Simons Postdoctoral Fellowship
- Simons Foundation grant [594598]
- [U01-AR073159]
Obesity can lead to dysfunction of the antimicrobial function of reactive dermal adipogenesis, which increases susceptibility to skin infections. Therapeutic targets such as TGF beta receptor inhibitors and peroxisome proliferator-activated receptor-gamma agonists can help manage skin infections associated with obesity.
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-beta (TGF beta) by mature adipocytes that then inhibited adipocyte progenitors and the production of cathelicidin in vitro. Administration of a TGF beta receptor inhibitor or a peroxisome proliferator-activated receptor-gamma 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.
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