Speksin: Metabolizmanın Yeni Modülatörü
Özet
Galanin/kisspeptin/speksin ailesinin bir üyesi olan speksin (nöropeptit Q), 12. kromozomdaki C12orf39 geni tarafından kodlanan ve sinyal peptitlerinin kesilmesiyle 14 amino asitten oluşan yaklaşık 1.6 kDa ağırlığında aktif bir peptit hormondur. Merkezi sinir sistemi ile karaciğer, böbrek, kalp, akciğer, mide, pankreas ve adipoz doku gibi birçok yapıda geniş bir ekspresyon yelpazesine sahip olan speksin, GALR2 ve GALR3 reseptörlerine özgün bir ligand olarak bağlanıp hücre içi sinyalizasyonu başlatır. Hücre içi mekanizmalarda PI3K/Akt yolağını aktive eder, L-tipi voltaj bağımlı kalsiyum kanalları (L-VDCC) aracılığıyla sitoplazmik kalsiyum düzeylerini düzenler ve TNF-α, IL-1β, IL-6 ile NF-κB gibi pro-enflamatuvar faktörleri baskılayarak anti-enflamatuvar etkiler sergiler. Ayrıca hipoksik kardiyomiyositlerde mitokondriyal hasarı engelleyerek PPAR-α, PGC1-α ve TFAM düzeylerini korur. Speksin; gıda alımını azaltan anoreksijenik etkisi, oksijen tüketimi ile fiziksel aktiviteyi artırması ve solunum değişim oranını düşürmesi sayesinde enerji homeostazı, glukoz ve lipit metabolizmasında kritik rol oynar. Obezite, Tip 1 ve Tip 2 diyabet, metabolik sendrom, non-alkolik karaciğer yağlanması (NAFLD) ve polikistik over sendromu (PCOS) gibi patolojik durumlarda dolaşımdaki speksin seviyelerinin belirgin şekilde düştüğü; açlık kan glukozu, HbA1c, HOMA-IR, trigliserit ve kolesterol değerleri ile negatif korelasyon gösterdiği saptanmıştır. Bu özellikleri sayesinde speksin, obezite ve kronik metabolik hastalıkların önlenmesi ve tedavisinde gelecekte kullanılabilecek potansiyel bir terapötik ajandır.
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