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Effect of miR-696 e miR-let7b on the mitochondrial function in insulin resistant muscle cells

Grant number: 13/22733-0
Support Opportunities:Regular Research Grants
Duration: October 01, 2014 - March 31, 2017
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Leonardo dos Reis Silveira
Grantee:Leonardo dos Reis Silveira
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Insulin resistance is a feature associate with type II diabetes but its mechanism is not fully understood. Recently, micro-RNAs (miRNAs) have been described as non-coding molecules associated with post-transcriptional gene regulation and, therefore, regulate several physiological and pathological processes like growth, differentiation, metabolism, cancer and diabetes. It is known that the miR-696 regulates Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1±), involved in mitochondrial biogenesis. Our previous study shown that in diabetic rats, the miRNA let-7b regulates the protein Akt1. Thus, we suggested that these miRNAs may be involved at insulin resistance of skeletal muscle cells. In fact, we have also observed a marked expression of miR-696 and miR-let7b in insulin resistant muscle cells. In contrast, inhibition of miR-696 and miR-let7b expression through antagomir lead to an increased mitochondrial oxygen consumption. This effect was reflected in improved insulin response. We are proposing, therefore, that reduction of miR-696 and miR-let7b expression might exert an important role on the muscle mitochondrial function indicating that miR-696 and miR-let7b might be important therapeutic target to the control of muscle insulin resistance and obesity. If our hypothesis is true, the overexpression of miR-696 in a trangenic mouse will lead to a reduced PGC1± expression and impairing the muscle mitochondrial biogenesis. (AU)

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Scientific publications (4)
(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)
SILVEIRA, LEONARDO R.; PAULETTI, BIANCA A.; LEME, ADRIANA F. PAES; LIMA, TANES I.. Seeking new molecular targets to control mitochondrial biogenesis. FASEB JOURNAL, v. 32, n. 1, p. 2-pg., . (16/23008-5, 13/22733-0)
ARAUJO, HYGOR N.; LIMA, I, TANES; GUIMARAES, DIMITRIUS SANTIAGO P. S. F.; OLIVEIRA, ANDRE G.; FAVERO-SANTOS, BIANCA C.; BRANCO, RENATO C. S.; DA SILVA ARAUJO, RAFAELA MARIANO; DANTAS, ALVARO F. B.; CASTRO, ALEX; CHACON-MIKAHIL, MARA PATRICIA T.; et al. Regulation of Lin28a-miRNA let-7b-5p pathway in skeletal muscle cells by peroxisome proliferator-activated receptor delta. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, v. 319, n. 3, p. C541-C551, . (13/22733-0, 16/23008-5)
QUEIROZ, ANDRE L.; LESSARD, SARAH J.; OUCHIDA, AMANDA T.; ARAUJO, HYGOR N.; GONCALVES, DAWIT A.; GUIMARAES, DIMITRIUS SANTIAGO P. SIMOES FREES; TEODORO, BRUNO G.; SO, KAWAI; ESPREA, ENILZA M.; HIRSHMAN, MICHAEL F.; et al. The MicroRNA miR-696 is regulated by SNARK and reduces mitochondrial activity in mouse skeletal muscle through Pgc1 alpha inhibition. MOLECULAR METABOLISM, v. 51, . (13/22733-0)
LIMA, TANES I.; ARAUJO, HYGOR N.; MENEZES, EVELINE S.; SPONTON, CARLOS H.; ARAUJO, MICHEL B.; BOMFIM, LUCAS H. M.; QUEIROZ, ANDRE L.; PASSOS, MADLA A.; AMARAL E SOUSA, THAIS; HIRABARA, SANDRO M.; et al. Role of microRNAs on the Regulation of Mitochondrial Biogenesis and Insulin Signaling in Skeletal Muscle. Journal of Cellular Physiology, v. 232, n. 5, p. 958-966, . (13/22733-0)

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