Sıçanlarda sirkadiyen ritim bozuklukları ile ilgili çeşitli koşulların plazma ve eritrosit lipidleri üzerindeki etkileri: peroksizomal bir bakış açısı

Öz

Amaç: Lipidomik çalışmalar; sirkadiyen ritim bozukluklarıyla ilişkili olduğu bilinen uyku kısıtlamasının karaciğer peroksizomlarında sentezlenen plazmalojenler dahil olmak üzere bazı plazma fosfolipid düzeylerinde değişikliklere neden olduğunu ortaya koymuştur. Bu nedenle bu çalışmada, sirkadiyen ritim bozukluklarına neden olduğu bilinen çeşitli koşulların bazı peroksizomal parametreler üzerindeki etkilerinin araştırılması ve bu etkilerin, bir peroksizom proliferatör reseptör agonisti olan fenofibrat ile karşılaştırılması amaçlandı. Gereç ve yöntem: Eritrosit lizatlarındaki plazmalojenler ve bazı yağ asitleri GC ile analiz edildi. Plazmadaki çok uzun zincirli yağ asitlerinin yanı sıra fitanik ve pristanik asitleri içeren peroksizomal metabolitler GC-MS ile ölçüldü. Karaciğer kesitlerinde katalaz antikorları ile immünohistolojik analizler gerçekleştirildi. Bulgular: Test edilen tüm koşullar, kontrollere kıyasla karaciğer kesitlerinde artmış katalaz immünoreaktivitesi gösterdi. Hem kalori kısıtlaması, hem de zaman kısıtlamalı beslenme, ayrıca fenofibrat tedavisi, eritrosit lizatlarında daha düşük C18:0 plazmalojen içeriğini sergiledi. Plazmalogenlerin peroksizomlar tarafından sentezlendiği bilindiğinden, mevcut sonuçlar, eritrosit membranındaki peroksizomal lipit içeriğinin, sirkadiyen ritim bozukluklarından etkilenebileceğini göstermektedir. Sonuç: Sirkadiyen ritim bozuklukları ve fenofibratın peroksizomal indüksiyonunun eritrosit membran lipidleri üzerindeki ortak etkileri, bunlar arasında bir bağlantı olduğunu göstermektedir.

Anahtar Kelimeler

• Kalori kısıtlaması
• sirkadiyen ritim
• fenofibrat
• peroksizom
• plazmalojen

Effects of various conditions related to circadian rhythm disturbances on plasma and erythrocyte lipids in rats: a peroxisomal perspective

Öz

Purpose: Lipidomics studies of sleep restriction, which is known to be associated with circadian perturbations, revealed alterations in some plasma phospholipid levels including plasmalogens which are partly synthesized in liver peroxisomes. To this end it was aimed to investigate effects of various conditions known to cause circadian rhythm disturbances on various peroxisomal parameters and to compare those effects with that of fenofibrate, a peroxisome proliferator-activated receptor alpha agonist. Materials and methods: Plasmalogens and some fatty acids in erythrocyte lysates were analyzed by GC. Peroxisomal metabolites including very long chain fatty acids as well as phytanic and pristanic acids in plasma were measured by GC-MS. Immunohistological analyses by catalase antibodies were conducted on liver sections. Results: All the conditions tested exhibited increased catalase immunoreactivity in liver sections compared to that of controls. Both calorie restriction, time-restricted feeding, as well as fenofibrate treatment exhibited lower C18:0 plasmalogen contents of erythrocyte lysates. As plasmalogens are known to be synthesized by peroxisomes, the present results suggest that the peroxisomal lipid content in membranes might be affected by conditions co-occuring with circadian perturbations. Conclusion: Shared effects of conditions associated with circadian rhythm disturbances and peroxisomal induction by fenofibrate on erythrocyte membrane lipids might indicate a link between them.

Anahtar Kelimeler

• Calorie restriction
• circadian rhythm
• fenofibrate
• peroxisome
• plasmalogen

Kaynakça

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