Peroxisome Proliferator-Activated Receptor α (PPARα) Activators, Bezafibrate and Wy-14,643, Increase Uncoupling Protein-3 mRNA Levels without Modifying the Mitochondrial Membrane Potential in Primary Culture of Rat Preadipocytes
| Autor: | Manuel Vázquez, Rosa M. Sánchez, Juan C. Laguna, Tomás Adzet, Àgatha Cabrero, Marta Alegret |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Biophysics Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor Biochemistry Ion Channels Membrane Potentials Mitochondrial Proteins Internal medicine Adipocytes medicine Animals Uncoupling Protein 3 Uncoupling protein RNA Messenger Inner mitochondrial membrane Electrochemical gradient Molecular Biology Cells Cultured DNA Primers Membrane potential chemistry.chemical_classification Messenger RNA Bezafibrate Base Sequence ATP synthase biology Stem Cells Mitochondria Rats Pyrimidines Endocrinology chemistry biology.protein Peroxisome Proliferators Carrier Proteins Transcription Factors medicine.drug |
| Zdroj: | Archives of Biochemistry and Biophysics. 380:353-359 |
| ISSN: | 0003-9861 |
| DOI: | 10.1006/abbi.2000.1927 |
| Popis: | Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters which act as pores for H(+) ions, dissipating the electrochemical gradient that develops during mitochondrial respiration at the expense of ATP synthesis. We have studied the effects of two fibrates, bezafibrate and Wy-14,643, on UCP-3 and UCP-2 mRNA levels in primary monolayer cultures of rat adipocytes and undifferentiated preadipocytes. Treatment with both PPARalpha activators for 24 h up-regulated UCP-3 mRNA levels. Thus, bezafibrate treatment resulted in an 8-fold induction in UCP-3 mRNA levels in preadipocytes compared with the 3.5-fold induction observed in adipocytes. Differences in the induction of UCP-3 between these cells correlated well with the higher expression of PPARalpha and RXRalpha mRNA values in preadipocytes compared to adipocytes. Wy-14,643 caused similar effects on UCP-3 mRNA expression. In contrast to UCP-3, UCP-2 mRNA levels were only slightly modified by bezafibrate in adipocytes. The induction in UCP-3 expression was not accompanied by changes in the mitochondrial membrane potential of rat primary preadipocytes after bezafibrate or Wy-14,643 treatment. Since it has been proposed that UCP-3 could be involved in the regulation of the use of fatty acids as fuel substrates, the UCP-3 induction achieved after bezafibrate and Wy-14, 643 treatment may indicate a higher oxidation of fatty acids, limiting their availability to be stored as triglycerides. This change may result in a reduced rate of conversion of preadipocytes to adipocytes, which directly affects fat depots. |
| Databáze: | OpenAIRE |
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