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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

ntramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mic

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Author(s):
Rodrigues, Alice C. [1] ; Spagnol, Alexandre R. [1] ; Frias, Flavia de Toledo [1] ; de Mendonca, Mariana [1] ; Araujo, Hygor N. [2, 3] ; Guimaraes, Dimitrius [2, 3] ; Silva, William J. [4] ; Bolin, Anaysa Paola [1] ; Murata, Gilson Masahiro [5] ; Silveira, Leonardo [2, 3]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Pharmacol, Sao Paulo - Brazil
[2] Obes & Comorbid Res Ctr OCRC, Campinas - Brazil
[3] Univ Estadual Campinas, UNICAMP, Dept Struct & Funct Biol, Inst Biol, Campinas - Brazil
[4] Univ Sao Paulo, Dept Anat, Inst Ciencias Biomed, Sao Paulo - Brazil
[5] Univ Sao Paulo, Fac Med, Dept Med Clin, Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: FRONTIERS IN PHYSIOLOGY; v. 12, JUL 6 2021.
Web of Science Citations: 0
Abstract

The role of microRNAs in metabolic diseases has been recognized and modulation of them could be a promising strategy to treat obesity and obesity-related diseases. The major purpose of this study was to test the hypothesis that intramuscular miR-1 precursor replacement therapy could improve metabolic parameters of mice fed a high-fat diet. To this end, we first injected miR-1 precursor intramuscularly in high-fat diet-fed mice and evaluated glucose tolerance, insulin sensitivity, and adiposity. miR-1-treated mice did not lose weight but had improved insulin sensitivity measured by insulin tolerance test. Next, using an in vitro model of insulin resistance by treating C2C12 cells with palmitic acid (PA), we overexpressed miR-1 and measured p-Akt content and the transcription levels of a protein related to fatty acid oxidation. We found that miR-1 could not restore insulin sensitivity in C2C12 cells, as indicated by p-Akt levels and that miR-1 increased expression of Pgc1a and Cpt1b in PA-treated cells, suggesting a possible role of miR-1 in mitochondrial respiration. Finally, we analyzed mitochondrial oxygen consumption in primary skeletal muscle cells treated with PA and transfected with or without miR-1 mimic. PA-treated cells showed reduced basal respiration, oxygen consumption rate-linked ATP production, maximal and spare capacity, and miR-1 overexpression could prevent impairments in mitochondrial respiration. Our data suggest a role of miR-1 in systemic insulin sensitivity and a new function of miR-1 in regulating mitochondrial respiration in skeletal muscle. (AU)

FAPESP's process: 20/08049-2 - Circulating microRNAs as mediators of metabolic adaptation promoted by aerobic exercise in obesity
Grantee:Alice Cristina Rodrigues
Support type: Regular Research Grants
FAPESP's process: 11/05876-6 - Role of microRNAs in the development of insulin resistance
Grantee:Alice Cristina Rodrigues
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 17/19513-9 - Role of microRNAs in the regulation of adipokines and myocynes: understanding molecular mechanisms involved in the interaction between adipose tissue and skeletal muscle
Grantee:Mariana de Mendonça
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 18/07087-8 - The role of microRNAs in metabolic alterations promoted by diet-induced obesity or maternal obesity
Grantee:Alice Cristina Rodrigues
Support type: Regular Research Grants
FAPESP's process: 18/07241-7 - microRNAs participation in adipose tissue plasticity induced by iatrogenic chronic hypercortisolism
Grantee:Anaysa Paola Bolin
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/24789-8 - MicroRNAs on adiponectin signalling: potential therapeutical targets of insulin resistance and insulin resistance linked diseases.
Grantee:Alice Cristina Rodrigues
Support type: Regular Research Grants