Interference of TSPO upon the activation pathways of 3T3-L1 adipocytes

Author(s)

Éric Diego Barioni

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2018-02-02

Examining board members

Maurício Yonamine; Niels Olsen Saraiva Câmara; Fabio Bessa Lima

• Advisor: Sandra Helena Poliselli Farsky

Abstract

Obesity is associated with a chronic low-grade inflammation and these represents one of the risk factors to development of other non-communicable diseases. TSPO 18 kDa is involved in several cellular functions, including biosynthesis and steroids transport, porphyrin transport, apoptosis, heme biosynthesis, oxidative metabolism and immunomodulation. Furthermore, the TSPO expression and function on adipose tissue and in the chronic low-grade inflammation have not been established. Thus, the aim of present study was to validate the TSPO expression and function on the 3T3-L1 differentiation process and to investigate whether diazepam treatment is able to modulate the TNF-α induced inflammatory effects on 3T3-L1 cells. Our results showed that diazepam treatment of preadipocytes was not able to modulate the adipogenesis. However, although diazepam treatment per se does not modulate the triacylglycerol accumulation and gene and protein expression of PPAR-γ; in TNF-α stimulated adipocytes, the treatment with diazepam was able to modulate the decreased of PPAR-γ gene and protein expression induced by TNF-α. In addition, the diazepam treatment of adipocytes was able to positively modulate the TSPO protein expression, an effect that we did not observe in cells treated with clonazepam, a central benzodiazepine ligand. In summary, the data obtained in this study, for the first time, demonstrate the possible relationship between the pathways that control the TSPO, TNF-α and PPAR-γ signaling. Thus, it is possible that the activation of TSPO by diazepam was able to modulate TNF-α-induced activation of NF-kB, promoting the reduction of lipolysis and increased of TSPO gene expression and PPAR-γ gene and protein expression, reestablishment of cellular homeostasis, which would increase cell survival, mitochondrial activity, and adipogenic activity of adipocytes. (AU)

• FAPESP's process: 13/11027-7 - TSPO INTERFERENCE ON THE PATHWAY OF ACTIVATION OF 3T3-L1 ADIPOCYTES LINEAGE
• Grantee: Eric Diego Barioni
• Support Opportunities: Scholarships in Brazil - Doctorate