EFFECTS OF CADMIUM ON HUMAN PRE-ADIPOCYTES

• Grant number: 23/12836-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Isabel Cardoso Alonso-Vale
• Grantee: Raphael Justa Saran
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

In addition to the dysfunctions of adipose tissue (AT) caused by lipid excess, such as thosefound in obesity, recent literature has shown that AT is a target of toxicity from certain metals. Morespecifically, heavy metals cadmium and mercury have gained considerable attention due to theircritical role in the development of various metabolic-endocrine disorders, promoting the developmentof cardiovascular diseases and diabetes mellitus. During adipogenesis, the process of differentiationof mesenchymal stem cells (adipose stem cells - ASCs) into adipocytes, epigenetic changes involvinglysine 27 of histone 3 (H3K27) are critical for the silencing and activation of transcription factorsresponsible for ASC impairment. Ezh2 is responsible for H3K27 trimethylation and gene silencing,while Crebbp and Ep300 (Cbp/p300) are responsible for acetylation, leading to transcriptionactivation. Between silencing and activation, the action of demethylases Kdm6a and Kdm6b isrequired. This study aims to investigate the effects of the heavy metal cadmium on epigeneticmodifications in human ASCs. For this purpose, ASCs present in the vascular stroma (VS) fraction ofvisceral and/or subcutaneous AT collected from patients during elective surgeries will be cultured andexposed in vitro to cadmium (3 and 10 µM) for 24 and 48 hours. They will then be used forexperiments employing real-time RT-PCR and western blotting methods to assess alterations inepigenetic marks in pre-adipocytes, including the expression of H3K27-modifying transcripts and/orproteins (H3K27me3, H3K27ac, Crebbp, Ep300, Kdm6A, Kdm6b).

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SIMAO, JUSSARA DE JESUS; BISPO, ANDRESSA FRANCA DE SOUSA; PLATA, VICTOR TADEU GONCALVES; ABEL, ANA BEATRIZ MARQUES; SARAN, RAPHAEL JUSTA; BARCELLA, JULIA FERNANDES; ALONSO, JOAO CARLOS CARDOSO; SANTANA, ANDRE VALENTE; ARMELIN-CORREA, LUCIA MARIA; ALONSO-VALE, MARIA ISABEL CARDOSO. The Activation of the NF-κB Pathway in Human Adipose-Derived Stem Cells Alters the Deposition of Epigenetic Marks on H3K27 and Is Modulated by Fish Oil. LIFE-BASEL, v. 14, n. 12, p. 17-pg., 2024-12-01. (23/12836-8, 19/13618-9, 22/15127-5, 19/26240-4, 23/12708-0)