Decreased levels and activity of Sirt1 are modulated by increased miR-34a expression in adipose tissue mononuclear cells from subjects with overweight and obesity: A pilot study

• Published in: Diabetes & metabolic syndrome clinical research & reviews 2020-09, Vol.14 (5), p.1347-1354
• Main Authors: Briones-Espinoza, Margarita J., Cortés-García, Juan D., Vega-Cárdenas, Mariela, Uresti-Rivera, Edith U., Gómez-Otero, Arturo, López-López, Nallely, Mejía-Torres, Manuel, Portales-Pérez, Diana P.
• Format: Article
• Language: English
• Subjects: Metabolic targets; microRNA; Obesity; Overweight; Sirtuin
• ISSN: 1871-4021; 1878-0334
• DOI: 10.1016/j.dsx.2020.07.014

Overweight and obesity are important risk factors for chronic disorders. Fat accumulation is one of the central manifestations; it occurs via a complex mechanism where multiple metabolic signals converge. Sirtuins are an enzyme family with deacetylase functions that are implicated in the regulation of several genes. Sirt1 and its upstream regulator (miR-34a) are elements of a converging mechanism that integrates the dynamic metabolic state. In this work, we hypothesized that elevated levels of miR-34a in overweight/obese group inhibits Sirt1 activity. Therefore, we studied the miR-34a/Sirt1 axis in mononuclear cells obtained from adipose tissue. Adipose tissue samples were collected from 36 subjects, and they were categorized according to body mass index (BMI) as overweight/obesity and normoweight. Subcutaneous adipose tissue samples were enzymatically dissociated, and mononuclear cells from adipose tissue were isolated by Ficoll Hypaque. Sirt1-positive cells and relative Sirt1 expression were determined by flow cytometry and real-time polymerase chain reaction (qPCR), respectively. Finally, Sirt1 activity was measured with a luminescence assay. The percentage of Sirt1-positive mononuclear cells from adipose tissue decreased along with Sirt1 enzymatic activity in overweight/obese participants. miR-34a expression increased in the overweight/obese group compared to normoweight individuals. There was a negative association between the relative miR-34a expression and Sirt1-positive cells and a synergistic effect on Sirt1-positive cells mediated by the miR-34a inhibitor and Sirt1 agonist. Our results describe for the first time the presence of miR-34a and Sirt1 in mononuclear cells isolated from subcutaneous adipose tissue. Additionally, these results suggest altered sirtuin function in overweight/obese patients and open the possibility for new therapies that involve these metabolic targets. •Sirt1 is downregulated and miR-34 levels are increased in subcutaneous adipose tissue mononuclear cells from obese subjects.•A negative correlation between miR-34 and Sirt1 expression in obese subjects was found.•Sirt1 function could be a target for new therapies to molecules involved in the metabolism of obese subjects.