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Sex differences on adipose tissue remodeling: from molecular mechanisms to therapeutic interventions

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Abstract

Sexual dimorphism greatly influences adipose tissue remodeling, which is characterized by changes in the activity, number, and/or size of adipocytes in response to distinct stimuli, including lifestyle and anti-obesity drugs. This sex dependence seems to be due to the anatomical and endocrine disparities between men and women. At the molecular level, sex hormones are believed to mediate such differences and involve estrogen and androgen receptor-induced gene expression. The signaling pathways that regulate adipose tissue metabolism and function include peroxisome proliferator-activated receptor gamma, uncoupling protein 1 (UCP1), 5’ adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial oxidative phosphorylation (OXPHOS), among other molecular players. Sex hormone-related pathways also interplay with adrenergic signaling, probably the most well-characterized molecular mechanism implicated in the remodeling of white adipose tissue. This review overviews and integrates the signaling pathways behind sexual dimorphism in adipose tissue remodeling, hoping to increase the knowledge on the pathogenesis of diseases, such as obesity and related comorbidities, and consequently, to drive future studies to investigate the regulation of this tissue homeostasis, either in men or women.

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Acknowledgments

This work was supported by the University of Aveiro and Portuguese Foundation for Science and Technology/Ministry of Science and Technology, FCT/MCT, for the financial support for the LAQV (FCT UIDB/50006/2020), CIAFEL (UIDB/00617/2020), iBiMED (UID/BIM/04501/2019), and UnIC (UID/IC/00051/2019) research units and the research projects RUNawayPCa (POCI-01-0145-FEDER-006958 and PTDC/DTP-DES/6077/2014) and NETDIAMOND (POCI-01-0145-FEDER-016385) and the post-graduation student (grant number SFRH/BD/144396/2019) to A.M.P. through national funds and co-financed by the European Regional Development Fund (ERDF), within the PT2020 Partnership Agreement.

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Correspondence to Alexandra Moreira-Pais.

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Moreira-Pais, A., Ferreira, R., Neves, J.S. et al. Sex differences on adipose tissue remodeling: from molecular mechanisms to therapeutic interventions. J Mol Med 98, 483–493 (2020). https://doi.org/10.1007/s00109-020-01890-2

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