Role of microRNAs on control of adiponectin gene expression

• Grant number: 15/24650-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2016
• Effective date (End): December 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Alice Cristina Rodrigues
• Grantee: Mariana de Mendonça
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Adiponectin is an adipokine mainly secreted by adipocytes and it plays an important role in metabolic regulation; and its production is abnormal in several situations such as insulin resistance associated with obesity. Despite the widespread evidence of their role in metabolism, little is known about mechanisms involved in controlling its expression. Recently, there are evidences that adiponectin gene and its receptors might be regulated by microRNAs (miRs), therefore a treatment that regulates the expression of these miRs can be effective in the improvement of insulin resistance. Pioglitazone is an agonist of peroxisome proliferator-activated receptor (PPAR) alpha and gamma that induces the production of adiponectin and ameliorate insulin resistance. Adipose tissue appears to be the main target for PPAR gamma agonists, but clinical and pre-clinical studies point skeletal muscle as well as a target. Recent studies in our laboratory with C57BL / 6 mice fed a high fat diet for 8 weeks to induce insulin resistance, showed increased expression of adiponectin and its AdipoR2 receptor in skeletal muscle after treatment with pioglitazone. The treatment was also associated to a down-regulation of expression of microRNAs (miRs), miR-23b and miR-222. Therefore, this project aims to to evaluate in animal models knockout for adiponectin if treatment with pioglitazone restores insulin sensitivity and if this improvement is also associated with the regulation of miR-23b expression and miR-222 in skeletal muscle. Finally, we propose to elucidate the mechanism by which microRNAs might regulate adiponectin expression in cell culture.

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)

DE MENDONCA, MARIANA; CARDOSO DOS SANTOS, BRUNA DE ARAUJO; DE SOUSA, ERICA; RODRIGUES, ALICE CRISTINA. Adiponectin is required for pioglitazone-induced improvements in hepatic steatosis in mice fed a high-fat diet. Molecular and Cellular Endocrinology, v. 493, AUG 1 2019. (15/24650-0, 15/24789-8)

DE MENDONCA, MARIANA; DE SOUSA, ERICA; DA PAIXAO, AILMA O.; DOS SANTOS, BRUNA ARAUJO; SPAGNOL, ALEXANDRE ROVERATTI; MURATA, GILSON M.; ARAUJO, HYGOR N.; DE LIMA, TANES IMAMURA; PASSOS SIMOES FROES GUIMARAES, DIMITRIUS SANTIAGO; SILVEIRA, LEONARDO R.; et al. MicroRNA miR-222 mediates pioglitazone beneficial effects on skeletal muscle of diet-induced obese mice. Molecular and Cellular Endocrinology, v. 501, FEB 5 2020. (14/22046-5, 15/24789-8, 11/05876-6, 15/24650-0)