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Long-term inhibition of miR-21 leads to reduction of obesity in db/db mice.
Seeger, Timon; Fischer, Ariane; Muhly-Reinholz, Marion; Zeiher, Andreas M; Dimmeler, Stefanie.
Afiliación
  • Seeger T; Institute for Cardiovascular Regeneration, Center of Molecular Medicine, University of Frankfurt, Frankfurt, Germany; Department of Cardiology, Internal Medicine III, University of Frankfurt, Frankfurt, Germany.
Obesity (Silver Spring) ; 22(11): 2352-60, 2014 Nov.
Article en En | MEDLINE | ID: mdl-25141837
OBJECTIVE: To assess the effect of long-term pharmacological inhibition of miR-21 in a model of metabolic syndrome and obesity. METHODS: Aged db/db mice were treated with locked nucleic acid-modified anti-miRs directed against miR-21 (LNA-21), control LNAs or PBS for 18 weeks. Cardiac function was assessed by echocardiography and the effect on body weight and white adipose tissue (WAT) was evaluated. RESULTS: MiR-21 expression was efficiently inhibited in the heart and WAT with no apparent liver toxicity or deterioration of kidney function. MiR-21 inhibition had no effect on cardiac hypertrophy as well as systolic and diastolic cardiac functions. However, levels of cardiac collagen 1 were modestly reduced in LNA-21 treated mice. MiR-21 inhibition reduced body weight, as well as adipocyte size and serum triglycerides were significantly decreased. The miR-21 targets TGFß-receptor 2 (TGFBR2) and phosphatase and tensin homolog (PTEN) were derepressed in WAT of LNA-21 treated mice and Sprouty1 and 2 were increased after miR-21 inhibition. CONCLUSIONS: Long-term treatment with LNA-21 is safe and efficiently suppresses miR-21 expression. Cardiac function was not affected. LNA-21 treatment led to a significant weight loss and reduces adipocyte size as well as derepression of the targets TGFRB2, PTEN, and Sprouty1 and 2.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: MicroARNs / Obesidad Límite: Animals Idioma: En Revista: Obesity (Silver Spring) Asunto de la revista: CIENCIAS DA NUTRICAO / FISIOLOGIA / METABOLISMO Año: 2014 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: MicroARNs / Obesidad Límite: Animals Idioma: En Revista: Obesity (Silver Spring) Asunto de la revista: CIENCIAS DA NUTRICAO / FISIOLOGIA / METABOLISMO Año: 2014 Tipo del documento: Article País de afiliación: Alemania