Endocrine Abstracts

Background and aim: Obesity is a chronic disease associated with a positive energy balance leading to lipotoxicity, which contributes to the onset of obesity-associated metabolic disorders such as type 2 diabetes and insulin resistance. It’s well known that thermogenesis in brown adipose tissue (BAT) and “browning” of white AT (WAT) increase energy expenditure, thus promoting weight loss and protect against obesity. Recently, the microRNAs (miRNAs) that regulate thermogenesis and browning are acquiring great interest. In addition, several studies have reported that miR-21 regulate adipogenesis and could be associated with obesity. Recently, our group have demonstrated that miR-21 mimic decreases body weight by inducing thermogenesis and browning of WAT in animal model. Thus, the aim of the present study was to associate miR-21 with gold nanoparticle; which could be a good tool to deliver this miRNA to WAT; to evaluate the nanosystem citotoxicity, and to analyze its effect on body weight gain, browning and thermogenesis.

Materials and methods: The cytotoxicity evaluation of nanosystem was carried out by microscopic study and by analyzing the short and long-term effect of miR-21 mimic/Au@ treatment on blood composition of C57BL/6J mice. In addition, the effect of this nanosystem on body weight gain and on thermogenic and browning markers expression was evaluated.

Results: We observed that hematological and biochemical parameters values did not shown any significant differences between control and treated mice groups. Moreover, no tissue damage nor accumulation of nanoparticles in the organs from miR-21-mimic/An@ treated mice. In parallel, this nanosystem significantly decreased body weight gain of obese mice and increased the expression levels of browning and thermogenic markers Ucp1, Tmem26, Pgc1-a, Prdm16 y Vegf-A in WAT.

Conclusion: Our results suggest the potential role of mimic-miR-21/Au@ nanosystem as a possible and efficient treatment against obesity and type 2 diabetes.This work was supported by grants from: Instituto de Salud Carlos III (ISCIII)/FEDER-UE (PI18/00785) and Consejería de Transformación Económica, Industria, Conocimiento y Universidades Dirección General de Investigación y Transferencia del Conocimiento (PY20-01274) co-funded by Fondo Europeo de Desarrollo Regional–FEDER.S.L. is a recipient of a post-doctoral grant Plan Andaluz de Investigación, Desarrollo e Innovación (DOC-01138) from Consejería de Economía, Conocimiento, Empresas y Universidades.R.E.B. is under a contract from the ‘Nicolas Monarde’ (C-0030-2016) program from the Servicio Andaluz de Salud, Regional Ministry of Health of the Andalusian Government, Andalusia