Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema

Mauro Vasella; Stefan Wolf; Eamon C Francis; Gerrit Grieb; Pablo Pfister; Gregory Reid; Jürgen Bernhagen; Nicole Lindenblatt; Epameinondas Gousopoulos; Bong-Sung Kim

doi:10.3390/metabo13101105

Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema

Metabolites. 2023 Oct 23;13(10):1105. doi: 10.3390/metabo13101105.

Authors

Affiliations

¹ Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland.
² Department of Plastic and Reconstructive Surgery, Guys and St Thomas Trust, London SE1 7EH, UK.
³ Department of Plastic Surgery and Hand Surgery, Gemeinschaftskrankenhaus Havelhoehe, 14089 Berlin, Germany.
⁴ Department of Plastic Surgery, Hand Surgery and Burn Center, University Hospital RWTH Aachen, 52074 Aachen, Germany.
⁵ Department of Surgery, Stadtspital Zürich Triemli, 8063 Zurich, Switzerland.
⁶ Division of Vascular Biology, Institute for Stroke and Dementia Research (ISD), Ludwig-Maximilians-University (LMU), 81377 Munich, Germany.
⁷ Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
⁸ Munich Heart Alliance, German Centre for Cardiovascular Diseases, 80802 Munich, Germany.

Abstract

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74-a common receptor for both cytokines-was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema.

Keywords: CD74; cytokine; lipedema; macrophage migration inhibitory factor.

Grants and funding

Bong-Sung Kim is sponsored by the German Research Foundation (Deutsche Forschungsgemeinschaft, KI 1973/2-1). Epameinodas Gousopoulos is sponsored by the Lipedema Foundation Grant (Nr. 27A). Jürgen Bernhagen received funding from grants DFG SFB1123-A3 and DFG BE1977/11-1.