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Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood.

Llobet L, Toivonen JM, Montoya J, Ruiz-Pesini E, López-Gallardo E - Dis Model Mech (2015)

Bottom Line: We have analyzed the effects on adipocyte differentiation of some xenobiotics that act on the oxidative phosphorylation system.The tested concentrations have been previously reported in human blood.Our results show that pharmaceutical drugs that decrease mitochondrial DNA replication, such as nucleoside reverse transcriptase inhibitors, or inhibitors of mitochondrial protein synthesis, such as ribosomal antibiotics, diminish adipocyte differentiation and leptin secretion.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, 50013-Zaragoza, Spain Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, 50013-Zaragoza, Spain CIBER de Enfermedades Raras (CIBERER), Universidad de Zaragoza, 50013-Zaragoza, Spain.

No MeSH data available.


Related in: MedlinePlus

Adipogenic differentiation. (A) Expression of hASC marker mRNAs. White and gray bars represent hASCs and adipocytes, respectively. *P=0.0035. (B,C) Representative optical (B) and electron microscopy (C) images of hASCs. (D,E) Representative optical (D) and electron microscopy (D) images of adipocytes. (F) Cell protein amount. White and gray bars represent the protein quantity per million cells of hASCs and adipocytes, respectively. *P=0.0314. (G,H) Representative microscopy images of adipocytes stained with Nile Red (G) or Oil Red O (H). (I) Cell triglyceride levels. White and gray bars represent the quantity of triglycerides in hASCs and adipocytes, respectively. *P<0.0001. (J) Expression of PPARγ mRNA. White and gray bars represent hASCs and adipocytes, respectively. *P=0.0442. (K) Representative immunocytochemical image of adipocytes FABP4. (L) Adipokine levels secreted by adipocytes. Dotted line represents the levels found in the hASC culture medium. *P≤0.0117.
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DMM021774F3: Adipogenic differentiation. (A) Expression of hASC marker mRNAs. White and gray bars represent hASCs and adipocytes, respectively. *P=0.0035. (B,C) Representative optical (B) and electron microscopy (C) images of hASCs. (D,E) Representative optical (D) and electron microscopy (D) images of adipocytes. (F) Cell protein amount. White and gray bars represent the protein quantity per million cells of hASCs and adipocytes, respectively. *P=0.0314. (G,H) Representative microscopy images of adipocytes stained with Nile Red (G) or Oil Red O (H). (I) Cell triglyceride levels. White and gray bars represent the quantity of triglycerides in hASCs and adipocytes, respectively. *P<0.0001. (J) Expression of PPARγ mRNA. White and gray bars represent hASCs and adipocytes, respectively. *P=0.0442. (K) Representative immunocytochemical image of adipocytes FABP4. (L) Adipokine levels secreted by adipocytes. Dotted line represents the levels found in the hASC culture medium. *P≤0.0117.

Mentions: As expected, adipogenic differentiation medium slowed hASC proliferation. The mRNA levels of hASC marker proteins CD90 and CD105 decreased by 57.4% and 40.8%, respectively (Fig. 3A). The onset of differentiation was not completely synchronized and, as previously reported (Hofmann et al., 2012; Keuper et al., 2014), a certain percentage of the cells (approximately 50% in our case) did not differentiate at all. Compared with undifferentiated hASCs (Fig. 3B,C), differentiated cells showed a morphological change and increased volume (Fig. 3D,E) which, at times, has been reported to be as high as 20-fold (von Heimburg et al., 2005). The increased size was only partially associated with higher protein content (Fig. 3F) and mainly represented accumulation of lipid droplets, as shown by lipophilic staining (Fig. 3G,H) and triglyceride assay (Fig. 3I). The appearance of lipid droplets is a clear indicator of adipocyte differentiation.Fig. 3.


Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood.

Llobet L, Toivonen JM, Montoya J, Ruiz-Pesini E, López-Gallardo E - Dis Model Mech (2015)

Adipogenic differentiation. (A) Expression of hASC marker mRNAs. White and gray bars represent hASCs and adipocytes, respectively. *P=0.0035. (B,C) Representative optical (B) and electron microscopy (C) images of hASCs. (D,E) Representative optical (D) and electron microscopy (D) images of adipocytes. (F) Cell protein amount. White and gray bars represent the protein quantity per million cells of hASCs and adipocytes, respectively. *P=0.0314. (G,H) Representative microscopy images of adipocytes stained with Nile Red (G) or Oil Red O (H). (I) Cell triglyceride levels. White and gray bars represent the quantity of triglycerides in hASCs and adipocytes, respectively. *P<0.0001. (J) Expression of PPARγ mRNA. White and gray bars represent hASCs and adipocytes, respectively. *P=0.0442. (K) Representative immunocytochemical image of adipocytes FABP4. (L) Adipokine levels secreted by adipocytes. Dotted line represents the levels found in the hASC culture medium. *P≤0.0117.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631789&req=5

DMM021774F3: Adipogenic differentiation. (A) Expression of hASC marker mRNAs. White and gray bars represent hASCs and adipocytes, respectively. *P=0.0035. (B,C) Representative optical (B) and electron microscopy (C) images of hASCs. (D,E) Representative optical (D) and electron microscopy (D) images of adipocytes. (F) Cell protein amount. White and gray bars represent the protein quantity per million cells of hASCs and adipocytes, respectively. *P=0.0314. (G,H) Representative microscopy images of adipocytes stained with Nile Red (G) or Oil Red O (H). (I) Cell triglyceride levels. White and gray bars represent the quantity of triglycerides in hASCs and adipocytes, respectively. *P<0.0001. (J) Expression of PPARγ mRNA. White and gray bars represent hASCs and adipocytes, respectively. *P=0.0442. (K) Representative immunocytochemical image of adipocytes FABP4. (L) Adipokine levels secreted by adipocytes. Dotted line represents the levels found in the hASC culture medium. *P≤0.0117.
Mentions: As expected, adipogenic differentiation medium slowed hASC proliferation. The mRNA levels of hASC marker proteins CD90 and CD105 decreased by 57.4% and 40.8%, respectively (Fig. 3A). The onset of differentiation was not completely synchronized and, as previously reported (Hofmann et al., 2012; Keuper et al., 2014), a certain percentage of the cells (approximately 50% in our case) did not differentiate at all. Compared with undifferentiated hASCs (Fig. 3B,C), differentiated cells showed a morphological change and increased volume (Fig. 3D,E) which, at times, has been reported to be as high as 20-fold (von Heimburg et al., 2005). The increased size was only partially associated with higher protein content (Fig. 3F) and mainly represented accumulation of lipid droplets, as shown by lipophilic staining (Fig. 3G,H) and triglyceride assay (Fig. 3I). The appearance of lipid droplets is a clear indicator of adipocyte differentiation.Fig. 3.

Bottom Line: We have analyzed the effects on adipocyte differentiation of some xenobiotics that act on the oxidative phosphorylation system.The tested concentrations have been previously reported in human blood.Our results show that pharmaceutical drugs that decrease mitochondrial DNA replication, such as nucleoside reverse transcriptase inhibitors, or inhibitors of mitochondrial protein synthesis, such as ribosomal antibiotics, diminish adipocyte differentiation and leptin secretion.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, 50013-Zaragoza, Spain Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, 50013-Zaragoza, Spain CIBER de Enfermedades Raras (CIBERER), Universidad de Zaragoza, 50013-Zaragoza, Spain.

No MeSH data available.


Related in: MedlinePlus