PGC-1α mediates differentiation of mesenchymal stem cells to brown adipose cells

Pin L. Huang, Yu Chih Chen, Li Hsin Chen, Chi Chang Juan, Hung Hai Ku, Shih Tien Wang, Shih Hwa Chiou, Guang Yuh Chiou, Chin Wen Chi, Chuan Chih Hsu, Hsin Chen Lee, Liang Kung Chen, Chung Lan Kao

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Aim: Mesenchymal stem cells (MSCs) are a multipotent cell type that can differentiate into nonhematopoietic 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.

Original languageEnglish
Pages (from-to)966-980
Number of pages15
JournalJournal of Atherosclerosis and Thrombosis
Volume18
Issue number11
Publication statusPublished - 2011
Externally publishedYes

Fingerprint

Stem cells
Mesenchymal Stromal Cells
Brown Adipose Tissue
Fats
Adipocytes
White Adipose Tissue
Organelle Biogenesis
Tissue
Adenoviridae
Adipogenesis
Mammals
Cytochromes
Electron Transport
Energy balance
Lipid Metabolism
Osteogenesis
Oxygen Consumption
Energy Metabolism
Reactive Oxygen Species
Respiration

Keywords

  • Adipogenesis
  • Brown adipose cells
  • Mesenchymal stem cells
  • PGC-1α

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Internal Medicine
  • Biochemistry, medical

Cite this

Huang, P. L., Chen, Y. C., Chen, L. H., Juan, C. C., Ku, H. H., Wang, S. T., ... Kao, C. L. (2011). PGC-1α mediates differentiation of mesenchymal stem cells to brown adipose cells. Journal of Atherosclerosis and Thrombosis, 18(11), 966-980.

PGC-1α mediates differentiation of mesenchymal stem cells to brown adipose cells. / Huang, Pin L.; Chen, Yu Chih; Chen, Li Hsin; Juan, Chi Chang; Ku, Hung Hai; Wang, Shih Tien; Chiou, Shih Hwa; Chiou, Guang Yuh; Chi, Chin Wen; Hsu, Chuan Chih; Lee, Hsin Chen; Chen, Liang Kung; Kao, Chung Lan.

In: Journal of Atherosclerosis and Thrombosis, Vol. 18, No. 11, 2011, p. 966-980.

Research output: Contribution to journalArticle

Huang, PL, Chen, YC, Chen, LH, Juan, CC, Ku, HH, Wang, ST, Chiou, SH, Chiou, GY, Chi, CW, Hsu, CC, Lee, HC, Chen, LK & Kao, CL 2011, 'PGC-1α mediates differentiation of mesenchymal stem cells to brown adipose cells', Journal of Atherosclerosis and Thrombosis, vol. 18, no. 11, pp. 966-980.
Huang PL, Chen YC, Chen LH, Juan CC, Ku HH, Wang ST et al. PGC-1α mediates differentiation of mesenchymal stem cells to brown adipose cells. Journal of Atherosclerosis and Thrombosis. 2011;18(11):966-980.
Huang, Pin L. ; Chen, Yu Chih ; Chen, Li Hsin ; Juan, Chi Chang ; Ku, Hung Hai ; Wang, Shih Tien ; Chiou, Shih Hwa ; Chiou, Guang Yuh ; Chi, Chin Wen ; Hsu, Chuan Chih ; Lee, Hsin Chen ; Chen, Liang Kung ; Kao, Chung Lan. / PGC-1α mediates differentiation of mesenchymal stem cells to brown adipose cells. In: Journal of Atherosclerosis and Thrombosis. 2011 ; Vol. 18, No. 11. pp. 966-980.
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T1 - PGC-1α mediates differentiation of mesenchymal stem cells to brown adipose cells

AU - Huang, Pin L.

AU - Chen, Yu Chih

AU - Chen, Li Hsin

AU - Juan, Chi Chang

AU - Ku, Hung Hai

AU - Wang, Shih Tien

AU - Chiou, Shih Hwa

AU - Chiou, Guang Yuh

AU - Chi, Chin Wen

AU - Hsu, Chuan Chih

AU - Lee, Hsin Chen

AU - Chen, Liang Kung

AU - Kao, Chung Lan

PY - 2011

Y1 - 2011

N2 - Aim: Mesenchymal stem cells (MSCs) are a multipotent cell type that can differentiate into nonhematopoietic 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.

AB - Aim: Mesenchymal stem cells (MSCs) are a multipotent cell type that can differentiate into nonhematopoietic 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.

KW - Adipogenesis

KW - Brown adipose cells

KW - Mesenchymal stem cells

KW - PGC-1α

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