Obesity has increased dramatically over the past decades. In addition to its detrimental effects on metabolism and the cardiovascular system, obesity also disrupts immune and inflammatory responses, promoting inflammatory and autoimmune processes. For instance, obesity exacerbates the severity of many inflammatory diseases, such as psoriasis—a chronic inflammatory skin disorder. These facts highlight the magnitude of the challenge and the need to understand the relationship between obesity and inflammation.
In our laboratory, we investigate the connection between obesity and inflammatory skin diseases such as psoriasis. Recently, using mouse models and in vitro approaches, we demonstrated that saturated fatty acids and the protein S100A9 are key factors contributing to obesity-related enhancement of skin inflammation. These findings are now being translated into clinical studies.
Mechanisms of Obesity-Induced Exacerbation of Inflammatory Responses in the Skin
A) Obesity or a high-fat diet leads to an increase in saturated fatty acids (SFA), which under homeostatic conditions have no effect on the skin.
B) The release of S100A9 during injury/inflammation, in the absence of elevated SFAs, does not promote activation of macrophages/monocytes.
C) During injury or inflammation, S100A9 is released. The binding of S100A9 to TLR4 and subsequent activation of NF-κB induces the gene expression of IL-1β in macrophages. In the presence of elevated SFAs—such as occurs with obesity or a high-fat diet—the inflammasome in these cells is activated, leading to the release of IL-1β. IL-1β released by macrophages in turn enhances the expression of S100A9 in the epidermis and in dermal white adipose tissue (dWAT), thereby triggering a sustained S100A9 response during skin inflammation. Additionally, S100A9 impairs macrophage activation and polarization, thus preventing the resolution of skin inflammation. This ultimately contributes to chronic and intensified skin inflammation and impaired tissue repair.
(From: Franz S, Ertel A, Engel KM, Simon JC, Saalbach A. Theranostics. 2022; 12: 1659–82.)
Publications
- Modulation of Dietary Fatty Acids in an Open-Label Study Improves Psoriasis and Dampens the Inflammatory Activation Status. Nutrients. 2023;
- Overexpression of S100A9 in obesity impairs macrophage differentiation via TLR4-NFkB-signaling worsening inflammation and wound healing. Theranostics. 2022; 12: 1659–82.
- Psoriasis: Obesity and Fatty Acids. Front Immunol. 2019; 10: 1807.
- High-Fat Diet Exacerbates Early Psoriatic Skin Inflammation Independent of Obesity: Saturated Fatty Acids as Key Players. J Invest Dermatol. 2018; 138: 1999–2009.
