Unlocking the thermogenic program in mature white adipocytes through transdifferentiation

• Grant number: 24/20562-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2025
• End date: July 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Carlos Henrique Grossi Sponton
• Grantee: Flávia Caroline Gan
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/15025-5 - Unveiling the PRDM16 transcriptional complex related to the inhibition of ceramides synthesis genes in adipocytes, AP.JP

Abstract

Brown and beige adipocytes play a crucial role in regulating energy metabolism in mammals by dissipating energy in the form of heat through thermogenesis. While brown adipocytes are established during the prenatal period, beige adipocytes are induced postnatally in response to stimuli such as cold exposure and pharmacological agents. The formation of beige adipocytes is described by two mechanisms: de novo adipogenesis, through the differentiation of local precursors; and transdifferentiation, where white adipocytes directly convert into beige adipocytes. Despite advances in understanding de novo differentiation processes, the molecular mechanisms regulating transdifferentiation remain poorly understood. This study aims to identify the transcriptional factors responsible related to whote to beige adipocyte transition using CRISPR activation technology (CRISPRa). Our preliminary results show the establishment of a reporter mouse line (Adipo-SPH-PhAM) and a white adipocyte cell model (5F-W), which will be used for identifying and validating, respectively, the transcriptional mediators responsible for the transdifferentiation of white adipocytes into beige adipocytes. The project aims to open new possibilities for developing therapies that can reverse the metabolic dysfunction observed in obesity by modulating adipose tissue and improving energy homeostasis.