Aneta Cierzniak1, Dorota Pawelka2, Krzysztof Kaliszewski3, Jerzy Rudnicki3, Tadeusz Dobosz4, Malgorzata Malodobra-Mazur4. 1. Department of Forensic Medicine, Molecular Techniques Unit, Wroclaw Medical University, Curie-Sklodowskiej 52, 50-369, Wroclaw, Poland. aneta.cierzniak@student.umed.wroc.pl. 2. Department and Division of Surgical Didactics, Wroclaw Medical University, M. Curie-Sklodowskiej 66, 50-369, Wroclaw, Poland. 3. Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland. 4. Department of Forensic Medicine, Molecular Techniques Unit, Wroclaw Medical University, Curie-Sklodowskiej 52, 50-369, Wroclaw, Poland.
Abstract
OBJECTIVE: Both obesity and insulin resistance are characterized by severe long-term changes in the expression of many genes of importance in the regulation of metabolism. Because these changes occur throughout life, as a result of external factors, the disorders of gene expression could be epigenetically regulated. MATERIALS/ METHODS: We analyzed the relationship between obesity and insulin resistance in enrolled patients by means of evaluation of the expression rate of numerous genes involved in the regulation of adipocyte metabolism and energy homeostasis in subcutaneous and visceral adipose tissue depots. We also investigated global and site-specific DNA methylation as one of the main regulators of gene expression. Visceral and subcutaneous adipose tissue biopsies were collected from 45 patients during abdominal surgery in an age range of 40-60 years. RESULTS: We demonstrated hypermethylation of PPARG, INSR, SLC2A4, and ADIPOQ promoters in obese patients with insulin resistance. Moreover, the methylation rate showed a negative correlation with the expression of the investigated genes. More, we showed a correlation between the expression of PPARG and the expression of numerous genes important for proper insulin action. Given the impact of PPARγ on the regulation of the cell insulin sensitivity through modulation of insulin pathway genes expression, hypermethylation in the PPARG promoter region may constitute one of the epigenetic pathways in the development of insulin resistance in obesity. CONCLUSIONS: Our research shows that epigenetic regulation through excessive methylation may constitute a link between obesity and subsequent insulin resistance.
OBJECTIVE: Both obesity and insulin resistance are characterized by severe long-term changes in the expression of many genes of importance in the regulation of metabolism. Because these changes occur throughout life, as a result of external factors, the disorders of gene expression could be epigenetically regulated. MATERIALS/ METHODS: We analyzed the relationship between obesity and insulin resistance in enrolled patients by means of evaluation of the expression rate of numerous genes involved in the regulation of adipocyte metabolism and energy homeostasis in subcutaneous and visceral adipose tissue depots. We also investigated global and site-specific DNA methylation as one of the main regulators of gene expression. Visceral and subcutaneous adipose tissue biopsies were collected from 45 patients during abdominal surgery in an age range of 40-60 years. RESULTS: We demonstrated hypermethylation of PPARG, INSR, SLC2A4, and ADIPOQ promoters in obese patients with insulin resistance. Moreover, the methylation rate showed a negative correlation with the expression of the investigated genes. More, we showed a correlation between the expression of PPARG and the expression of numerous genes important for proper insulin action. Given the impact of PPARγ on the regulation of the cell insulin sensitivity through modulation of insulin pathway genes expression, hypermethylation in the PPARG promoter region may constitute one of the epigenetic pathways in the development of insulin resistance in obesity. CONCLUSIONS: Our research shows that epigenetic regulation through excessive methylation may constitute a link between obesity and subsequent insulin resistance.
Authors: Francesca Remelli; Elisa Maietti; Pasquale Abete; Giuseppe Bellelli; Mario Bo; Antonio Cherubini; Francesco Corica; Mauro Di Bari; Marcello Maggio; Maria Rosaria Rizzo; Andrea P Rossi; Francesco Landi; Stefano Volpato Journal: Aging Clin Exp Res Date: 2021-08-16 Impact factor: 3.636