Neuromedin B receptor disruption impairs adipogenesis in mice and 3T3-L1 cells. (July 2019)

• Record Type: Journal Article
• Authors: de Paula, Gabriela Silva Monteiro; Wilieman, Marianna; Silva, Karina Ribeiro; Baptista, Leandra Santos; Boudina, Sihem; de Souza, Luana Lopes; Bento-Bernardes, Thais; Asensi, Karina Dutra; Goldenberg, Regina Coeli dos Santos; Pazos-Moura, Carmen Cabanelas
• Is Part Of: Journal of molecular endocrinology. Volume 63:Number 1(2019)
• Page Start: 93
• Page End: 102
• Publication Date: 2019-07
• Subjects: neuromedin B receptor -- adipogenesis -- neuromedin B receptor-knockout mice -- neuromedin B receptor antagonist -- 3T3-L1 cells; Molecular endocrinology -- Periodicals; Endocrinology -- Periodicals; 616.407
• DOI: 10.1530/JME-19-0032
• Languages: English
• ISSNs: 0952-5041

Abstract

Abstract : Neuromedin B, a bombesin-like peptide, and its receptor, are expressed in white adipose tissue with undefined roles. Female mice with disruption of neuromedin B receptor (NB-R) exhibited partial resistance to diet-induced obesity leading to our hypothesis that NB-R is involved in adipogenesis. Here, we showed that adipose stem/stromal cells (ASC) from perigonadal fat of female NB-R-knockout mice, exposed to a differentiation protocol in vitro, accumulated less lipid (45%) than wild type, suggesting reduced capacity to differentiate under adipogenic input. To further explore mechanisms, preadipocytes 3T3-L1 cells were incubated in the presence of NB-R antagonist (PD168368) during the first 3 days in culture. Cells were analyzed in the end of the treatment (Day 3) and later when fully differentiated (Day 21). NB-R antagonist induced lower number of cells at day 3 and 21 (33–39%), reduced cell proliferation at day 3 (−53%) and reduced lipid accumulation at day 21 (−86%). The mRNA expressions of several adipocyte differentiation markers were importantly reduced at both days: Cebpb and Pparg and Fabp4, Plin-1 and Adipoq, and additionally Lep mRNA at day 21. The antagonist had no effect when incubated with mature 3T3-L1 adipocytes. Therefore, genetically disruption of NB-R in mice ASC or pharmacological antagonism of NB-R in 3T3-L1 cells impairs adipogenesis. The mechanisms suggested by results in 3T3-L1 cells involve reduction of cell proliferation and of early gene expressions, leading to decreased number of mature adipocytes. We speculate that NB-R antagonism may be useful to limit the increase in adiposity due to pre-adipocyte differentiation.