RANKL induces beige adipocyte differentiation in preadipocytes. 2020

Flávia Sayuri Matsuo, and Paulo Henrique Cavalcanti de Araújo, and Ryerson Fonseca Mota, and Ana Júlia Rossoni Carvalho, and Mariana Santos de Queiroz, and Beatriz Baldo de Almeida, and Karen Cristine de Oliveira Santos Ferreira, and Rodrigo Jair Morandi Metzner, and Gustavo Duarte Ferrari, and Luciane Carla Alberici, and Mariana Kiomy Osako
Laboratory of Cell and Tissue Biology, Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil.

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.

UI MeSH Term Description Entries
D009765 Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D010101 Oxygen Consumption The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346) Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D002153 Calorimetry, Indirect Calculation of the energy expenditure in the form of heat production of the whole body or individual organs based on respiratory gas exchange. Calorimetry, Respiration,Calorimetries, Indirect,Calorimetries, Respiration,Indirect Calorimetries,Indirect Calorimetry,Respiration Calorimetries,Respiration Calorimetry
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D000069796 Adipose Tissue, Beige Brown fat-like adipose tissue that develops in WHITE ADIPOSE TISSUE from non-MYOGENIC REGULATORY FACTOR 5 expressing cell lineage. Adipose Tissue, Brite,Beige Adipose Tissue,Beige Brite Adipose Tissue,Beige Brite Fat,Beige Fat,Brite Adipose Tissue,Brite Fat,Adipose Tissues, Beige,Adipose Tissues, Brite,Beige Adipose Tissues,Beige Brite Fats,Brite Adipose Tissues,Brite Fat, Beige,Brite Fats, Beige,Fat, Beige,Fat, Beige Brite,Fat, Brite,Fats, Beige Brite,Tissue, Beige Adipose,Tissue, Brite Adipose,Tissues, Beige Adipose,Tissues, Brite Adipose
D000069797 Adipocytes, Beige Brown fat-like cells that develop in the WHITE FAT from non-MYOGENIC REGULATORY FACTOR 5 expressing CELL LINEAGE. Adipocytes, Brite,Beige Brite Adipocytes,Beige Brite Cells,Beige Fat Cells,Brite Fat Cells,Adipocyte, Beige,Adipocyte, Beige Brite,Adipocyte, Brite,Adipocytes, Beige Brite,Beige Adipocyte,Beige Adipocytes,Beige Brite Adipocyte,Beige Brite Cell,Beige Fat Cell,Brite Adipocyte,Brite Adipocyte, Beige,Brite Adipocytes,Brite Adipocytes, Beige,Brite Cell, Beige,Brite Cells, Beige,Brite Fat Cell,Cell, Beige Brite,Cell, Beige Fat,Cell, Brite Fat,Cells, Beige Brite,Cells, Beige Fat,Cells, Brite Fat,Fat Cell, Beige,Fat Cell, Brite,Fat Cells, Beige,Fat Cells, Brite
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015430 Weight Gain Increase in BODY WEIGHT over existing weight. Gain, Weight,Gains, Weight,Weight Gains
D050151 Subcutaneous Fat Fatty tissue under the SKIN through out the body. Adipose Tissue, Subcutaneous,Fat, Subcutaneous,Subcutaneous Adipose Tissue,Fats, Subcutaneous,Subcutaneous Fats

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