RANKL induces beige adipocyte differentiation in preadipocytes.
Flávia Sayuri MatsuoPaulo Henrique Cavalcanti de AraújoRyerson Fonseca MotaAna Júlia Rossoni CarvalhoMariana Santos de QueirozBeatriz Baldo de AlmeidaKaren Cristine de Oliveira Santos FerreiraRodrigo Jair Morandi MetznerGustavo Duarte FerrariLuciane Carla AlbericiMariana Kiomy OsakoPublished in: American journal of physiology. Endocrinology and metabolism (2020)
The receptor activator of nuclear factor-κB (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 with 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 with those from the 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 adipocytes, differentiated into beige adipose tissue in the presence of RANKL. Moreover, SVF cells, even under white adipocyte differentiation, showed multilocular 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.
Keyphrases
- nuclear factor
- high fat diet induced
- insulin resistance
- adipose tissue
- toll like receptor
- high fat diet
- type diabetes
- weight gain
- metabolic syndrome
- wild type
- skeletal muscle
- induced apoptosis
- poor prognosis
- cardiovascular disease
- bone loss
- cell cycle arrest
- glycemic control
- body mass index
- fatty acid
- inflammatory response
- oxidative stress
- genome wide
- high throughput
- low dose
- bone marrow
- pi k akt
- endothelial cells
- bone mineral density
- diabetic rats
- high glucose
- preterm birth
- transcription factor
- genome wide identification