title: PGC-1α mediates differentiation of mesenchymal stem cells to brown adipose cells.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) are a multipotent cell type that can differentiate into non-hematopoietic cells, such as adipocytes. Adipocyte tissue is central to the regulation of energy balance. Two functionally different types of fat are present in mammals. White adipose tissue is the primary site for triglyceride storage, while brown adipose tissue is specialized in energy expenditure. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) controls several aspects of mitochondrial biogenesis. In this study, we hypothesized that PGC-1α plays a role in brown fat differentiation of MSCs.
  
  
  METHODS
  Immortalized human MSCs were infected with adenovirus carrying PGC-1α cDNA to create PGC-1α-expressing MSCs.
  
  
  RESULTS
  The genetic profiling of PGC-1α-expressing MSCs shows the significant increase of genes related to mitochondrial functions and lipid metabolism compared to that of MSCs. When expressed in MSCs, PGC-1α activates robust mitochondrial biogenesis and respiration. The increase of oxygen consumption and reactive oxygen species represents a cellular readout of increased activity of the respiratory chain. The expression of thermogenic markers, such as cytochrome C and complex II, was significantly increased in MSCs with treatment of adenovirus expressing PGC-1α. Moreover, PGC-1α markedly inhibited the osteogenesis of MSCs under osteogenic induction. During adipogenesis, PGC-1α-expressing MSCs showed a significant increase in brown fat markers and a decrease in white fat markers. Notably, PGC-1α knockdown inhibited adipocyte differentiation of MSCs.
  
  
  CONCLUSIONS
  In summary, our data reveal an important role of PGC-1α in promoting brown fat differentiation of MSCs, and provide a new therapeutic approach for the treatment of obesity.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pin-I
authors.initials: PI
authors.lastname: Huang
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Chen
authors.forename: Li-Hsin
authors.initials: LH
authors.lastname: Chen
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Juan
authors.forename: Hung-Hai
authors.initials: HH
authors.lastname: Ku
authors.forename: Shih-Tien
authors.initials: ST
authors.lastname: Wang
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Guang-Yuh
authors.initials: GY
authors.lastname: Chiou
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
authors.forename: Chuan-Chih
authors.initials: CC
authors.lastname: Hsu
authors.forename: Hsin-Chen
authors.initials: HC
authors.lastname: Lee
authors.forename: Liang-Kung
authors.initials: LK
authors.lastname: Chen
authors.forename: Chung-Lan
authors.initials: CL
authors.lastname: Kao
mesh_terms: D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation; D019069:Cell Respiration; D004734:Energy Metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010101:Oxygen Consumption; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014157:Transcription Factors