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Effect of Glucagon-like Peptide-1 on the Differentiation of Adipose-derived Stem Cells into Osteoblasts and Adipocytes.

Lee HM, Joo BS, Lee CH, Kim HY, Ock JH, Lee YS - J Menopausal Med (2015)

Bottom Line: In contrast, GLP-1 significantly suppressed the expression of adipocyte-specific markers, peroxisome proliferator-activated receptor gamma (PPAR-γ), lipoprotein lipase (LPL) and adipocyte protein 2 (AP2).This decreased expression of adipocyte specific markers caused by GLP-1 was significantly reversed by the treatment of extracellular signal-regulated kinase (ERK) inhibitor, PD98059 (P < 0.05).This result demonstrates that GLP-1 stimulates osteoblast differentiation in ADSCs, whereas it inhibits adipocyte differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Natural Science College, Pusan National University, Busan, Korea.

ABSTRACT

Objectives: Glucagon-like peptide-1 (GLP-1) is an intestinally secreted hormone and it plays an important role in the regulation of glucose homeostasis. However, the possible role of GLP-1 in the differentiation of adipose-derived stem cells (ADSCs) remains unknown. Therefore this study investigated the effect of GLP-1 on the differentiation of ADSCs into osteoblasts and adipocytes.

Methods: ADSCs were isolated from human adipose tissues of the abdomens, cultured and characterized by flow cytometry and multi-lineage potential assay. ADSCs were induced in osteogenic and adipogenic media treated with two different doses (10 and 100 nM) of GLP-1, and then the effect of GLP-1 on differentiation of ADSCs into osteoblast and adipocyte was examined. The signaling pathway involved in these processes was also examined.

Results: Isolated human ADSCs expressed mesenchymal stem cell (MSC) specific markers as well as GLP-1 receptor (GLP-1R) proteins. They also showed multiple-lineage potential of MSC. GLP-1 was upregulated the activity and mRNA expression of osteoblast-specific marker, alkaline phosphatase and the mineralization of calcium. In contrast, GLP-1 significantly suppressed the expression of adipocyte-specific markers, peroxisome proliferator-activated receptor gamma (PPAR-γ), lipoprotein lipase (LPL) and adipocyte protein 2 (AP2). This decreased expression of adipocyte specific markers caused by GLP-1 was significantly reversed by the treatment of extracellular signal-regulated kinase (ERK) inhibitor, PD98059 (P < 0.05).

Conclusion: This result demonstrates that GLP-1 stimulates osteoblast differentiation in ADSCs, whereas it inhibits adipocyte differentiation. The ERK signaling pathway seems to be involved in these differentiation processes mediated by GLP-1.

No MeSH data available.


Effects of glucagon-like peptide-1 (GLP-1) on the adipogenic differentiation of adipose-derived stem cells (ADSCs). The ADSCs were induced to with adipogenic induction medium (AIM) with or without GLP-1 (0, 10 nM and 100 nM). (A, B) On day 14, cells were stained with oil red O to visualize lipid droplets. Original magnification, × 100. *P < 0.05 (vs. AIM). (C) On day 3 and 7, the mRNA levels of aP2, peroxisome proliferator-activated receptor (PPAR) and lipoprotein lipase (LPL) were determined by real time polymerase chain reaction (PCR). †P < 0.05 (vs. AIM).
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Figure 4: Effects of glucagon-like peptide-1 (GLP-1) on the adipogenic differentiation of adipose-derived stem cells (ADSCs). The ADSCs were induced to with adipogenic induction medium (AIM) with or without GLP-1 (0, 10 nM and 100 nM). (A, B) On day 14, cells were stained with oil red O to visualize lipid droplets. Original magnification, × 100. *P < 0.05 (vs. AIM). (C) On day 3 and 7, the mRNA levels of aP2, peroxisome proliferator-activated receptor (PPAR) and lipoprotein lipase (LPL) were determined by real time polymerase chain reaction (PCR). †P < 0.05 (vs. AIM).

Mentions: To examine the effect of GLP-1 on adipogenic differentiation in ADSCs, ADSCs cultured in AIM were treated with two doses of GLP-1 (10 nM and 100 nM). And then Oil-Red O staining and adipogenic specific gene expression were determined as an indicator for adipogenic differentiation. After 14 days of culture, the lipid accumulation by Oil Red O staining and quantitative analysis of lipid-droplet formation was decreased in a dose-dependent manner in response to GLP-1 treatment. Especially, a concentration of 100 nM GLP-1 significantly decreased the lipid accumulation compared to AIM without GLP-1 (Fig. 4A, 4B). Next, when the ADSCs were treated with 100 nM GLP-1 on day 0, 3 and 7 of culture, the expressions of AP2, PPAR-γ and LPL were significantly down-regulated at day 7 compared to AIM group (P < 0.05) (Fig. 4C). These data indicate that adipogenic differentiation of ADSCs may be inhibited by GLP-1.


Effect of Glucagon-like Peptide-1 on the Differentiation of Adipose-derived Stem Cells into Osteoblasts and Adipocytes.

Lee HM, Joo BS, Lee CH, Kim HY, Ock JH, Lee YS - J Menopausal Med (2015)

Effects of glucagon-like peptide-1 (GLP-1) on the adipogenic differentiation of adipose-derived stem cells (ADSCs). The ADSCs were induced to with adipogenic induction medium (AIM) with or without GLP-1 (0, 10 nM and 100 nM). (A, B) On day 14, cells were stained with oil red O to visualize lipid droplets. Original magnification, × 100. *P < 0.05 (vs. AIM). (C) On day 3 and 7, the mRNA levels of aP2, peroxisome proliferator-activated receptor (PPAR) and lipoprotein lipase (LPL) were determined by real time polymerase chain reaction (PCR). †P < 0.05 (vs. AIM).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4561747&req=5

Figure 4: Effects of glucagon-like peptide-1 (GLP-1) on the adipogenic differentiation of adipose-derived stem cells (ADSCs). The ADSCs were induced to with adipogenic induction medium (AIM) with or without GLP-1 (0, 10 nM and 100 nM). (A, B) On day 14, cells were stained with oil red O to visualize lipid droplets. Original magnification, × 100. *P < 0.05 (vs. AIM). (C) On day 3 and 7, the mRNA levels of aP2, peroxisome proliferator-activated receptor (PPAR) and lipoprotein lipase (LPL) were determined by real time polymerase chain reaction (PCR). †P < 0.05 (vs. AIM).
Mentions: To examine the effect of GLP-1 on adipogenic differentiation in ADSCs, ADSCs cultured in AIM were treated with two doses of GLP-1 (10 nM and 100 nM). And then Oil-Red O staining and adipogenic specific gene expression were determined as an indicator for adipogenic differentiation. After 14 days of culture, the lipid accumulation by Oil Red O staining and quantitative analysis of lipid-droplet formation was decreased in a dose-dependent manner in response to GLP-1 treatment. Especially, a concentration of 100 nM GLP-1 significantly decreased the lipid accumulation compared to AIM without GLP-1 (Fig. 4A, 4B). Next, when the ADSCs were treated with 100 nM GLP-1 on day 0, 3 and 7 of culture, the expressions of AP2, PPAR-γ and LPL were significantly down-regulated at day 7 compared to AIM group (P < 0.05) (Fig. 4C). These data indicate that adipogenic differentiation of ADSCs may be inhibited by GLP-1.

Bottom Line: In contrast, GLP-1 significantly suppressed the expression of adipocyte-specific markers, peroxisome proliferator-activated receptor gamma (PPAR-γ), lipoprotein lipase (LPL) and adipocyte protein 2 (AP2).This decreased expression of adipocyte specific markers caused by GLP-1 was significantly reversed by the treatment of extracellular signal-regulated kinase (ERK) inhibitor, PD98059 (P < 0.05).This result demonstrates that GLP-1 stimulates osteoblast differentiation in ADSCs, whereas it inhibits adipocyte differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Natural Science College, Pusan National University, Busan, Korea.

ABSTRACT

Objectives: Glucagon-like peptide-1 (GLP-1) is an intestinally secreted hormone and it plays an important role in the regulation of glucose homeostasis. However, the possible role of GLP-1 in the differentiation of adipose-derived stem cells (ADSCs) remains unknown. Therefore this study investigated the effect of GLP-1 on the differentiation of ADSCs into osteoblasts and adipocytes.

Methods: ADSCs were isolated from human adipose tissues of the abdomens, cultured and characterized by flow cytometry and multi-lineage potential assay. ADSCs were induced in osteogenic and adipogenic media treated with two different doses (10 and 100 nM) of GLP-1, and then the effect of GLP-1 on differentiation of ADSCs into osteoblast and adipocyte was examined. The signaling pathway involved in these processes was also examined.

Results: Isolated human ADSCs expressed mesenchymal stem cell (MSC) specific markers as well as GLP-1 receptor (GLP-1R) proteins. They also showed multiple-lineage potential of MSC. GLP-1 was upregulated the activity and mRNA expression of osteoblast-specific marker, alkaline phosphatase and the mineralization of calcium. In contrast, GLP-1 significantly suppressed the expression of adipocyte-specific markers, peroxisome proliferator-activated receptor gamma (PPAR-γ), lipoprotein lipase (LPL) and adipocyte protein 2 (AP2). This decreased expression of adipocyte specific markers caused by GLP-1 was significantly reversed by the treatment of extracellular signal-regulated kinase (ERK) inhibitor, PD98059 (P < 0.05).

Conclusion: This result demonstrates that GLP-1 stimulates osteoblast differentiation in ADSCs, whereas it inhibits adipocyte differentiation. The ERK signaling pathway seems to be involved in these differentiation processes mediated by GLP-1.

No MeSH data available.