MicroRNAs profile of serum extracellular vesicles and their possible involvement in energy metabolism regulation in obese animals.

Author(s)

Karina Cunha e Rocha

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2021-09-16

Examining board members

Alice Cristina Rodrigues; Bruna Brasil Brandão; Rosana Camarini; Lila Missae Oyama

• Advisor: Alice Cristina Rodrigues

Abstract

Cells can communicate with neighboring or distant cells through extracellular vesicles (EVs) that can carry microRNAs (miRNAs), small non-coding RNAs that regulate gene expression. Since the content of miRNAs and the number of EVs released by cells can be altered during obesity, we hypothesized that EVs from the serum of obese animals could regulate the energy metabolism of control animals by a possible transfer of miRNAs between different tissues. This work aimed to investigate the role of EVs in the regulation of energy metabolism in obesity and to identify possible EV-miRNAs involved in tissue communication. For this purpose, we induced obesity in male C57BL/6 mice with a high-fat diet supplemented with condensed milk for 12 weeks. Serum EVs were obtained from the obese mice and used to treat male C57BL/6 mice fed with a control diet. Compared to the control groups (animals treated with PBS and with serum EVs from control animals), EV treatment increased lipid oxidation preference, and decreased energy expenditure and heat. These results suggest that EVs released in the serum of obese animals can modulate the energy metabolism of control mice. Next, we performed sequencing of miRNAs EVs from a pool of serum samples from control and obese animals. After validating the miRNAs obtained from sequencing in individual samples, five miRNAs miR-22-3p, miR-29c-3p, miR-122-5p, miR-192-5p, and miR-802-5p were shown to be increased in serum EVs from obese animals. Analysis of the expression of these miRNAs in the liver, gastrocnemius muscle, and epididymal fat point to a possible communication between tissues through EV-miRNAs. Overall, our work shows the participation of serum EVs in the regulation of energy metabolism in obesity and describes potential EV-miRNAs contained in the serum EVs of obese individuals that may participate in tissue communication in obesity. (AU)

• FAPESP's process: 18/05426-0 - MicroRNAs as metabolic mediators in the communication among white adipose tissue, liver and skeletal muscle in obese mice
• Grantee: Karina Cunha e Rocha
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)