Understanding the relationship between Fibroblast growth factor 21 with total and visceral fat mass in major depressive disorder patients.

• Grant number: 25/22113-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: April 06, 2026
• End date: October 05, 2026
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Fabrício Eduardo Rossi
• Grantee: Jessenia Marise Sales Campos
• Supervisor: Marina Trombetta Lima
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
• Institution abroad: University Of Groningen,
• Associated to the scholarship: 24/18521-1 - Influence of resistance training volume on the reduction of depressive symptoms and indicators of self-efficacy in the exercise program in adults with major depressive disorder: a randomized clinical study., BP.MS

Abstract

Fibroblast growth factor 21 (FGF21) is a peptide hormone secreted by multiple organs, playing a key role in energy homeostasis, metabolic regulation, and nutrient preference. Preclinical evidence suggests its potential in treating obesity, a condition highly prevalent among individuals with major depressive disorder (MDD), with rates ranging from 50% to 63%. Recent findings indicate that FGF21 levels are elevated in MDD and interact with body mass index (BMI) to influence depression trajectories. However, BMI provides limited information on adiposity and may underestimate or overestimate obesity, highlighting the need for more precise indicators of body fat distribution. Specifically, central and visceral adiposity, often linked to systemic inflammation and increased mortality risk, may modulate both metabolic and neurobiological pathways involved in depression.This project aims to explore the relationship between circulating FGF21, fat mass distribution (total, trunk, android, and visceral fat), and neuroinflammation in patients with MDD. The study integrates two main approaches: (1) a clinical investigation assessing depressive symptoms, anthropometric and DXA-based body composition measures, blood biomarkers, and circulating FGF21 in adult patients with MDD, and (2) in vitro experiments to evaluate the effects of adipose tissue-derived secretome and recombinant FGF21 on microglial activity under basal and inflammatory conditions. Experimental outcomes will include cytokine release (TNF-¿, IL-6), phagocytic activity, and transcriptomic profiling via RNA sequencing.The originality of the study lies in combining exercise physiology, biomedical sciences, and advanced imaging to elucidate the interplay between adiposity, FGF21, and microglial function in the context of MDD. By correlating detailed body composition data with neuroinflammatory markers and FGF21 activity, the project aims to identify biological mechanisms underlying the comorbidity between obesity and depression, an area still insufficiently explored. The findings may reveal novel risk profiles and support the development of more effective, non-pharmacological strategies to address mental health in obese or metabolically compromised populations.Keywords: inflammation; body composition; mental health. (AU)