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Dis Model Mech. 2015 Nov;8(11):1441-55. doi: 10.1242/dmm.021774. Epub 2015 Sep 17.

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

Author information

1
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.
2
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.
3
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 Fundación ARAID, Universidad de Zaragoza, 50013-Zaragoza, Spain eduruiz@unizar.es esterlop@unizar.es.
4
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 eduruiz@unizar.es esterlop@unizar.es.

Abstract

Adipogenesis is accompanied by differentiation of adipose tissue-derived stem cells to adipocytes. As part of this differentiation, biogenesis of the oxidative phosphorylation system occurs. Many chemical compounds used in medicine, agriculture or other human activities affect oxidative phosphorylation function. Therefore, these xenobiotics could alter adipogenesis. 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. By contrast, the environmental chemical pollutant tributyltin chloride, which inhibits the ATP synthase of the oxidative phosphorylation system, can promote adipocyte differentiation and leptin secretion, leading to obesity and metabolic syndrome as postulated by the obesogen hypothesis.

KEYWORDS:

Adipocytes; OXPHOS; Xenobiotics

PMID:
26398948
PMCID:
PMC4631789
DOI:
10.1242/dmm.021774
[Indexed for MEDLINE]
Free PMC Article

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