Effects of Dicer overexpression on adipocyte differentiation

• Grant number: 14/12819-7
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2014
• Effective date (End): December 31, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Thiago Leite Knittel
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Obesity is a global epidemic. White adipocytes store fat while brown adipocytes are specialized in dissipating energy. Therefore, it has been proposed that the determination of the functional identity of the adipocyte is an important factor to maintain energy homeostasis and that the manipulation of this identity in favor of a brown fat signature can contribute to weight loss. Dicer is an enzyme that cleaves pre-miRNAs into mature miRNAs. It has been observed that this enzyme is important in adipose tissue for the differentiation of pre-adipocytes into adipocytes. Our results show that the knockout of Dicer in vitro in murine pre-adipocytes or in vivo in mouse adipose tissue leads to an identity shift, with brown adipocytes acquiring white adipocyte characteristics. These models also display a deficiency in ²-adrenergic response. Brown adipocytes express high levels of the miRNA processing pathway components and interventions that promote 'browning', such as cold exposure, ²-adrenergic stimulation and caloric restriction, increase Dicer expression in brown pre-adipocytes and subcutaneous white adipose tissue. Since these results indicate a correlation between reduced Dicer expression and a more white adipose tissue characteristics, we asked whether the opposite could be verified, i.e. if Dicer overexpression leads to brown adipocyte characteristics in mouse pre-adipocytes after differentiation. This intervention could lead to an efficient approach to increase energy expenditure and therefore prevent obesity.