Sex-Specific Epigenetic Regulation of miR-196 in Gonadal Adipose Tissue: The Role of Sex Hormones in Metabolic Function

• Grant number: 25/11392-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2026
• End date: January 31, 2029
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Luciana Pellegrini Pisani
• Grantee: Marcela Nascimento Sertorio
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

Gonadal adipose tissue exhibits marked sexual dimorphism, with metabolic and functional differences between males and females modulated by sex hormones. miR-196 regulates Hox family genes, which are involved in adipogenesis and body fat distribution. The sex-specific expression of miR-196 in gonadal adipose tissue remains poorly explored, representing a significant gap in the understanding of epigenetic regulation between sexes. Data from our previous murine studies revealed a sex-specific expression pattern of miR-196 associated with Hox gene modulation (FAPESP 2019/22635-4 - BPE and 2022/05377-4 - BEPE). This project aims to investigate whether miR-196 expression is regulated in a sex-specific manner by sex hormones, influencing metabolic differences under physiological conditions and diet-induced obesity. Male and female mice will be subjected to control or obesogenic diets for serum metabolic analysis (glucose, cholesterol, adiponectin, leptin, insulin, estradiol, testosterone, LH, and FSH) and assessment of miR-196 expression, Hox genes, adipogenic and thermogenic markers (C/EBP¿, Ppar¿, UCP1, PGC-1¿), hormone receptors (ER¿, ER¿, AR), and inflammatory cytokines (IL-10, IL-1¿, IL-6, TNF¿) in gonadal preadipocytes treated in vitro with estradiol or testosterone, as well as in mature adipocytes. The central hypothesis is that miR-196 regulation by sex hormones promotes sex-specific functional adaptations in gonadal adipose tissue, impacting metabolic homeostasis.