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Endothelin regulates intermittent hypoxia-induced lipolytic remodelling of adipose tissue and phosphorylation of hormone-sensitive lipase
- Source :
- 4.2 Sleep and Control of Breathing.
- Publication Year :
- 2015
- Publisher :
- European Respiratory Society, 2015.
-
Abstract
- Obstructive sleep apnea syndrome (OSA) is characterized by repetitive upper airway collapses during sleep inducing chronic intermittent hypoxia (IH). IH promotes adipose tissue remodelling and dyslipidaemia. Endothelin-1 (ET-1) production is upregulated by IH and may participate to changes in adipose tissue biology. Wistar rats were submitted to 14 days of IH (60-sec cycles alternating 21 and 5% FiO 2 , 8h/day) or control normoxia and treated or not with bosentan, a dual type A (ETA-R) and B (ETB-R) endothelin receptor antagonist. IH induced a lipolytic remodelling and a 2-fold increase in ET-1 transcription and ETA-R expression in adipose tissue that were reversed by bosentan. In 3T3-L1 adipocytes, ET-1 induced an upregulation of its own and of ETA-R transcription. Moreover, ET-1 promoted a glycerol release inhibited by bosentan and BQ123 (ETA-R antagonist) but not by BQ788 (ETB-R antagonist). Finally, bosentan reversed the ET-1-induced phosphorylation of Hormone-Sensitive Lipase (HSL) on Serine 660. ET-1 is thus involved in IH-induced lipolysis in Wistar rats, and upregulation of ET-1 production and ETA-R expression by ET-1 itself under IH could amplify its effects. ET-1-induced lipolysis appears to be mediated through ETA receptors and the activation of HSL by Serine 660 phosphorylation.
Details
- Database :
- OpenAIRE
- Journal :
- 4.2 Sleep and Control of Breathing
- Accession number :
- edsair.doi...........554aa5b74c8ba8bad6a3f623bf35ee44