Matsuo 2020 Am J Physiol Endocrinol Metab

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Matsuo FS, Araújo PHC, Mota RF, Carvalho AJR, Queiroz MS, Almeida BB, Ferreira KCOS, Metzner RJM, Ferrari GD, Alberici LC, Osako MK (2020) RANKL induces beige adipocyte differentiation in preadipocytes. Am J Physiol Endocrinol Metab 318:E866-77.

» PMID: 32315212

Matsuo FS, Araujo PHC, Mota RF, Carvalho AJR, Queiroz MS, Almeida BB, Ferreira KCOS, Metzner RJM, Ferrari GD, Alberici LC, Osako MK (2020) Am J Physiol Endocrinol Metab

Abstract: The receptor activator of nuclear factor kappa-B (NF-κB) (RANK), its ligand (RANKL) and the decoy receptor osteoprotegerin (OPG) are a triad of proteins that regulate bone metabolism, and serum OPG is considered a biomarker for cardiovascular diseases and type 2 diabetes, however the implications of OPG in adipose tissue metabolism remains elusive. In this study, we investigate RANK-RANKL-OPG signaling in white adipose tissue browning. Histological analysis of osteoprotegerin knockout (OPG-/-) mice showed subcutaneous white adipose tissue (sWAT) browning, resistance for high fat diet-induced weight gain, and preserved glucose metabolism compared to wild type (WT) mice. Stromal vascular fraction (SVF) cells from sWAT of OPG-/- mice showed multilocular morphology and higher expression of brown adipocyte marker genes compared to those from WT group. Infusion of RANKL induced browning and elevated respiratory rates in sWAT, along with increased whole-body oxygen consumption in mice measured by indirect calorimetry. Subcutaneous WAT-derived SVF and 3T3-L1 cells, but not mature white adipocyte, differentiated to beige in the presence of RANKL. Moreover, both cell types even under white adipocyte differentiation showed multiloculated lipid droplet, lower lipid content and increased expression of beige adipocyte markers with RANKL stimulation. In this study, we show for the first time the contribution of RANKL to increase energy expenditure by inducing beige adipocyte differentiation in preadipocytes.

Keywords: Beige adipocyte, Browning, OPG, RANK, RANKL Bioblast editor: Plangger M O2k-Network Lab: BR Ribeirao Preto Alberici LC


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Diabetes, Obesity 

Organism: Mouse  Tissue;cell: Fat  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k 

2020-04