title: Concomitant beige adipocyte differentiation upon induction of mesenchymal stem cells into brown adipocytes.
abstract: The accumulation of fat, which results in obesity, is related to many metabolic disorders. Besides white and brown adipose tissue, beige adipose tissue has recently been recognized as a new type of accumulated fat. Mesenchymal stem cells (MSCs) have been shown to differentiate into brown adipocytes. Through analyzing levels of mRNA and protein markers associated with beige adipocyte, we found concomitant beige adipocyte differentiation upon induction of MSCs into brown adipocytes in a defined medium containing triiodothyronine, insulin, dexamethasone, and indomethacin. Moreover, we found that protein kinase A (PKA) modulators regulated MSC differentiation into brown or beige adipocytes. Activation of PKA by isobutylmethylxanthine or forskolin increased brown adipocyte differentiation and reduced beige adipocyte differentiation, while inactivation of PKA by KT-5720 or SC-3010 or the knockdown of PKA downstream cAMP response element-binding protein (CREB) decreased brown adipocyte differentiation and increased beige adipocyte differentiation. We also showed that increased brown adipocyte differentiation was accompanied by an increase in mitochondrial mass. In conclusion, we propose a model of beige/brown co-differentiation in MSCs and develop a method for controlling this differentiation via PKA modulation.
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors: Yung-Li
authors: YL
authors: Wang
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors: Shih-Pei
authors: SP
authors: Lin
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
authors: Patrick C H
authors: PC
authors: Hsieh
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan; Integrative Stem Cell Center, Department of Orthopaedics, China Medical University Hospital, Taichung 404, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Department of Orthopaedics & Traumatology, Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan. Electronic address: hung3340@gmail.com.
authors: Shih-Chieh
authors: SC
authors: Hung
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000069797:Adipocytes, Beige / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D061251:Primary Cell Culture; D011758:Pyrroles / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: C115163:CREB1 protein, human; D002227:Carbazoles; D003470:Culture Media; D017362:Cyclic AMP Response Element-Binding Protein; D007328:Insulin; D011758:Pyrroles; D034741:RNA, Small Interfering; D014284:Triiodothyronine; D005576:Colforsin; C057416:KT 5720; D003907:Dexamethasone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin
keywords: Beige adipocyte; Brown adipocyte; MSCs; PKA