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MicroRNAs on adiponectin signalling: potential therapeutical targets of insulin resistance and insulin resistance linked diseases.

Grant number: 15/24789-8
Support type:Regular Research Grants
Duration: August 01, 2016 - July 31, 2018
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal researcher:Alice Cristina Rodrigues
Grantee:Alice Cristina Rodrigues
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Adiponectin is an adipokine produced and secreted, mainly by adipose tissue that has antidiabetic and antiatherogenic properties. Low levels of adiponectin are found in obesity and diabetis subjects. Adiponectin receptors, AdipoR1 and AdipoR2 are the major receptors for adiponectin, and they are key regulators of glucose and lipid metabolism. Adipor1/r2 double knockout mice abrogate adiponectin-binding and glucose-lowering effects of adiponectin, and result in high liver triglycerides content, insulin resistance and glucose intolerance. Both hipoadiponectinemia and low expression levels of AdipoR1 and R2 are associated to obesity and obesity-linked diseases such as diabetes mellitus type 2 and non-alcoholic fatty liver disease (NAFLD). Therefore, therapeutic interventions resulting in higher production of adiponectin and/or higher expression of AdipoRs may be important options to prevent obesity-linked diseases. Recently, post-transcriptionally regulation of Adiponectin (Adipoq) and Adipor1/r2 genes by microRNAs has been shown in obese humans and experimental obesity mice models. As well as this, many studies have demonstrated that a dysregulation of microRNAs expression may lead to insulin resistance and such studies have pointed circulating microRNAs as biomarkers of the progress of diabetes type 2 and NAFLD. Thu, the aim of our study is to find differentially expressed microRNAs in liver and skeletal muscle of DIO mice associated to adiponectin binding of Adipor1/r2 and serve as potential therapeutical targets to restore insulin resistance, and consequently treat or prevent diabetes type 2 and NAFLD. (AU)

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Scientific publications (7)
(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)
FERREIRA, LETICIA TORRES; BATISTA DE SOUSA FILHO, CELSO PEREIRA; MARINOVIC, MARCELO PARADISO; RODRIGUES, ALICE CRISTINA; OTTON, ROSEMARI. Green tea polyphenols positively impact hepatic metabolism of adiponectin-knockout lean mice. Journal of Functional Foods, v. 64, . (16/12059-8, 15/24789-8, 15/21785-1)
DA PAIXAO, AILMA O.; BOLIN, ANAYSA PAOLA; SILVESTRE, JOAO G.; RODRIGUES, ALICE CRISTINA. Palmitic Acid Impairs Myogenesis and Alters Temporal Expression of miR-133a and miR-206 in C2C12 Myoblasts. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 5, . (15/24789-8, 18/07087-8, 20/08049-2)
FRIAS, FLAVIA DE T.; ROCHA, KARINA C. E.; DE MENDONCA, MARIANA; MURATA, GILSON M.; ARAUJO, HYGOR N.; DE SOUSA, LUIS G. O.; DE SOUSA, ERICA; HIRABARA, SANDRO M.; LEITE, NAYARA DE C.; CARNEIRO, EVERARDO M.; et al. Fenofibrate reverses changes induced by high-fat diet on metabolism in mice muscle and visceral adipocytes. Journal of Cellular Physiology, v. 233, n. 4, p. 3515-3528, . (15/24789-8, 11/05876-6)
RODRIGUES, ALICE C.; SPAGNOL, ALEXANDRE R.; FRIAS, FLAVIA DE TOLEDO; DE MENDONCA, MARIANA; ARAUJO, HYGOR N.; GUIMARAES, DIMITRIUS; SILVA, WILLIAM J.; BOLIN, ANAYSA PAOLA; MURATA, GILSON MASAHIRO; SILVEIRA, LEONARDO. ntramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mic. FRONTIERS IN PHYSIOLOGY, v. 12, . (20/08049-2, 11/05876-6, 17/19513-9, 18/07087-8, 18/07241-7, 15/24789-8)
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, . (15/24789-8, 15/24650-0)
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, . (14/22046-5, 15/24789-8, 11/05876-6, 15/24650-0)
PEREIRA, BEATRIZ M. V.; THIEME, KARINA; DE ARAUJO, LARISSA; RODRIGUES, ALICE C.. Lack of adiponectin in mice accelerates high-fat diet-induced progression of chronic kidney disease. Life Sciences, v. 257, . (15/24789-8)

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