CD36-SREBP1 Axis Mediates TSLP Production in Obesity-Exacerbated Atopic Dermatitis

Obesity is associated with an increased risk of atopic dermatitis (AD) and may accelerate its development. Keratinocyte dysfunction has been observed in obesity-related skin diseases, including psoriasis and acanthosis nigricans, but is not fully understood in AD. In this study, we found that high-fat diet-induced obesity exac-erbated AD-like dermatitis in mice, with elevated inflammatory molecules and increased CD36-SREBP1-related fatty acid accumulation in the lesional skin. Blocking CD36 or SREBP1 with chemical inhibitors effectively alle-viated AD-like inflammation, decreased fatty acid accumulation, and downregulated TSLP expression in obese calcipotriol (MC903)-treated mice. Moreover, palmitic acid treatment induced TSLP overexpression in kerati-nocytes through the activation of the CD36-SREBP1 signaling pathway. The chromatin immunoprecipitation assay further revealed increased binding of SREBP1 to the TSLP promoter region. Our findings provide compelling evidence that obesity triggers the activation of the CD36-SREBP1-TSLP axis in keratinocytes, leading to epidermal lipid disorders and the aggravation of AD-like inflammation. By targeting CD36 or SREBP1, future combination therapies or modified treatment strategies could be developed to help manage patients with both obesity and AD.

Automated summary

This study found that obesity exacerbates AD-like dermatitis in mice, with increased inflammatory molecules and fatty acid accumulation in the skin. Blocking CD36 or SREBP1 effectively alleviates inflammation and fatty acid accumulation in AD, indicating the potential for targeted therapies. The activation of the CD36-SREBP1-TSLP axis in keratinocytes contributes to epidermal lipid disorders and aggravation of AD-like inflammation.