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Biochem Biophys Res Commun. 2016 Sep 16;478(2):689-95. doi: 10.1016/j.bbrc.2016.08.008. Epub 2016 Aug 3.

Concomitant beige adipocyte differentiation upon induction of mesenchymal stem cells into brown adipocytes.

Author information

1
Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.
2
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
3
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.

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.

KEYWORDS:

Beige adipocyte; Brown adipocyte; MSCs; PKA

PMID:
27498007
DOI:
10.1016/j.bbrc.2016.08.008
[Indexed for MEDLINE]

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