c-MAF dependent perivascular macrophages regulate diet induced metabolic syndrome

Moura Silva, H.; Kitoko, J. Z.; Queiroz, C. P.; Kroehling, L.; Matheis, F.; Lu Yang, K.; Ren-Fielding, C.; Littman, D.; Bozza, M.; Mucida, D.; Lafaille, J.

doi:10.1101/2021.02.07.430147

bioRxiv · 10.1101/2021.02.07.430147

c-MAF dependent perivascular macrophages regulate diet induced metabolic syndrome

Moura Silva, H.·Kitoko, J. Z.·Queiroz, C. P.·Kroehling, L.·Matheis, F.·Lu Yang, K.·Ren-Fielding, C.·Littman, D.·Bozza, M.·Mucida, D.·Lafaille, J.

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Abstract

Macrophages are an essential part of tissue development and physiology. Perivascular macrophages have been described in tissues and appear to play a role in development and disease processes, although it remains unclear what are the key features of these cells. Here, we identify a subpopulation of perivascular macrophages in several organs, characterized by their dependence on the transcription factor c-MAF, displaying non-conventional macrophage markers including LYVE1, Folate receptor 2 and CD38. Conditional deletion of c-MAF in macrophage lineages caused ablation of perivascular macrophages in the brain and altered muscularis macrophages program in the intestine. In the white adipose tissue (WAT), c-MAF deficient perivascular macrophages displayed an altered gene expression profile, which was linked to an increased vascular branching into the tissue. Upon feeding on high fat diet (HFD), mice with c-MAF deficient macrophages showed improved metabolic parameters compared to wild-type mice, including less weight gain, greater glucose tolerance and reduced inflammatory cell profile in WAT. These results define c-MAF as a central regulator of perivascular macrophages cell identity and transcriptional program in vivo and reveal a novel role for this tissue resident macrophage population in the regulation of metabolic syndrome.

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Moura Silva, H., Kitoko, J. Z., Queiroz, C. P., Kroehling, L., Matheis, F., Lu Yang, K., Ren-Fielding, C., Littman, D., Bozza, M., Mucida, D., Lafaille, J.. 2021-02-08. c-MAF dependent perivascular macrophages regulate diet induced metabolic syndrome. https://doi.org/10.1101/2021.02.07.430147

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