Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement

Abstract

// Reeta Kangas 1, * , Cristina Morsiani 2, * , Grazia Pizza 2, 3 , Catia Lanzarini 2 , Pauliina Aukee 4 , Jaakko Kaprio 5 , Sarianna Sipilä 1 , Claudio Franceschi 2 , Vuokko Kovanen 1 , Eija K. Laakkonen 1 and Miriam Capri 2, 6 1 Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland 2 DIMES-Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy 3 Epigenetics Program, Babraham Institute, Cambridge, United Kingdom 4 Department of Obstetrics and Gynecology, Pelvic Floor Research and Therapy Unit, Central Finland Central Hospital, Jyväskylä, Finland 5 Institute for Molecular Medicine Finland (FIMM) and Department of Public Health, University of Helsinki, Helsinki, Finland 6 CIG- Interdepartmental Centre “Galvani”, Via Petronio Vecchi, University of Bologna, Bologna, Italy * These authors have contributed equally to this work Correspondence to: Cristina Morsiani, email: cristina.morsiani2@unibo.it Keywords: microRNAs; miR-19a-3p; adipose tissue; aging; estrogen therapy Abbreviations: ESR1: estrogen receptor 1; AKT1: AKT serine/threonine kinase 1; BRAF: B-Raf proto-oncogene, serine/threonine kinase; BCL-2: B-cell lymphoma 2; CCND1: cyclin D1 Received: August 06, 2017     Accepted: December 04, 2017     Published: December 18, 2017 ABSTRACT Tissue-specific effects of 17β-estradiol are delivered via both estrogen receptors and microRNAs (miRs). Menopause is known to affect the whole-body fat distribution in women. This investigation aimed at identifying menopause- and hormone replacement therapy (HRT)-associated miR profiles and miR targets in subcutaneous abdominal adipose tissue and serum from the same women. A discovery phase using array technology was performed in 13 women, including monozygotic twin pairs discordant for HRT and premenopausal young controls. Seven miRs, expressed in both adipose tissue and serum, were selected for validation phase in 34 women from a different cohort. An age/menopause-related increase of miRs-16-5p, -451a, -223-3p, -18a-5p, -19a-3p,-486-5p and -363-3p was found in the adipose tissue, but not in serum. MiR-19a-3p, involved in adipocyte development and estrogen signaling, resulted to be higher in HRT users in comparison with non-users. Among the identified targets, AKT1, BCL-2 and BRAF proteins showed lower expression in both HRT and No HRT users in comparison with premenopausal women. Unexpectedly, ESR1 protein expression was not modified although its mRNA was lower in No HRT users compared to premenopausal women and HRT users. Thus, both HRT and menopause appear to affect adipose tissue homeostasis via miR-mediated mechanism.