Investigating the Role of Novel Mediators of Adipocyte Size in Human Cells

• Grant number: 24/10085-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 04, 2024
• End date: September 03, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Diogo de Moraes
• Supervisor: Yu-Hua Tseng
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 21/04048-4 - Search for new adipocyte size regulators, BP.DR

Abstract

Cardiometabolic diseases are a public health issue, and they have high incidence in the elderly and obese individuals. Among the demographic, anthropometric and histopathological characteristics associated with cardiometabolic disease risk, adipocyte size is more associated with diabetes than age or fat percentage. Larger adipocytes can limit the capacity of adipose tissue to store lipids, leading to dyslipidemia and ectopic lipid accumulation. Moreover, hypertrophied adipocytes can cause hypoxia and promote inflammation in the adipose tissue. These characteristics are found in individuals with cardiometabolic diseases, the obese and the elderly. Hypoxia-induced inflammation can also inhibit preadipocyte differentiation, possibly closing a vicious cycle that leads to limited adipogenic potential and results in metabolic dysfunction. Given this scenario, a better comprehension of adipocyte size regulation may help to understand and treat cardiometabolic conditions. My PhD thesis project aims to characterize genes that control adipocyte size. To do this, we have used public databases that contain the transcriptome and adipose tissue slides from heterogeneous human populations and found 27 genes associated with adipocyte size. Next, we validated if these genes are also associated with adipocyte size in independent human and mouse samples. Based on our validations and a literature review, we elected four genes - ITIH5, DHDDS, MMP28 and NPR3 - for functional analysis. In brief, we have been performing gain or loss-of-function assays to validate their capacity of regulating adipocyte size in vitro. In the present project, we want to further investigate the role of these genes in human adipocytes, leveraging the unique tools offered by the Tseng lab, including gene editing using human preadipocyte cell lines.