Primary cilia and obesity: mechanistic insights and therapeutic perspectives

Yıl 2026, Cilt: 19 Sayı: 1, 213 - 221, 30.03.2026

Yavuz Yavuz

https://izlik.org/JA24FY42AN

Öz

Primary cilia are sensory organelles that play a critical role in detecting and processing extracellular signals and have recently emerged as central regulators of energy homeostasis. Despite the rapid global rise in obesity prevalence, the molecular mechanisms governing energy intake and expenditure remain incompletely understood. In this context, primary cilia serve as a unique platform that spatially organizes key metabolic signaling pathways, including Hedgehog, Wnt/β-catenin, PDGF, and cAMP-dependent cascades. Disruption of ciliary integrity has been linked to metabolic phenotypes such as hyperphagia and reduced energy expenditure in hypothalamic neurons, abnormal differentiation and lipogenesis in adipocytes, and impaired glucose responsiveness in pancreatic β-cells. The severe obesity observed in ciliopathies such as Bardet–Biedl and Alström syndromes further underscores the essential role of ciliary function in maintaining metabolic health. At the molecular level, intraflagellar transport mechanisms, ciliary GPCR localization, and ADCY3-enriched cAMP microdomains shape the capacity of primary cilia to integrate metabolic signals. Perturbations in these processes exert multifaceted effects on energy balance across both central and peripheral tissues. Although cilia-targeted therapeutic approaches are theoretically promising, major translational challenges—including tissue specificity, long-term safety, and systemic effects—remain unresolved. This review summarizes the structural and functional properties of primary cilia, highlights their roles in metabolic regulation, and examines the molecular links between ciliary dysfunction and obesity. It also emphasizes the need for further mechanistic and translational studies to evaluate the feasibility of targeting primary cilia as a therapeutic strategy.

Anahtar Kelimeler

Primary cilia , obesity , ciliopathies , energy homeostasis , hypothalamus

Primer siliyer ve obezite: mekanistik yaklaşımlar ve terapötik perspektifler

https://izlik.org/JA24FY42AN

Öz

Primer siliyer (Primary cilia), hücre dışı sinyallerin algılanması ve işlenmesinde kritik rol oynayan duyusal organeller olup, son yıllarda enerji homeostazının düzenlenmesinde merkezi bir bileşen olarak öne çıkmıştır. Küresel obezite insidansındaki hızlı artışa rağmen, enerji alımı ve harcamasını belirleyen moleküler mekanizmalar tam olarak çözülememiştir. Bu bağlamda primer siliyer; Hedgehog, Wnt/β-katenin, PDGF ve cAMP-bağımlı yollar gibi metabolik açıdan belirleyici sinyal ağlarının organize edildiği özgün bir platform sunar. Siliyer bütünlüğün bozulması, hipotalamik nöronlarda hiperfaji ve azalmış enerji harcaması; adipositlerde anormal farklılaşma ve lipogenez; pankreatik β-hücrelerde ise glukoz yanıtında zayıflama gibi metabolik fenotiplerle ilişkilendirilmiştir. Bardet–Biedl ve Alström sendromu gibi siliyopati hastalıklarında görülen ağır obezite, siliyer fonksiyonların metabolik sağlık için vazgeçilmez olduğunu doğrulayan önemli klinik örneklerdir. Moleküler düzeyde, intraflagellar transport mekanizmaları, siliyer G proteinine bağlı reseptör (GPCR) dağılımı ve adenilat siklaz 3 (ADCY3) aracılı siklik adenozin monofosfat (cAMP) mikrobölgeleri, siliye’nin metabolik sinyalleri entegre etme kapasitesini şekillendirmektedir. Bu süreçlerdeki bozulmalar hem merkezi hem de periferik dokularda enerji dengesi üzerinde çok yönlü etkiler oluşturur. Siliyer hedefli terapötik yaklaşımlar teorik olarak umut verici olsa da dokuya özgüllük, uzun dönem güvenlik ve sistemik etkiler açısından önemli translasyonel kısıtlamalar mevcuttur. Bu derleme, primer siliyerin yapısal ve fonksiyonel özelliklerini, metabolik düzenlemedeki rollerini ve siliyer disfonksiyonun obeziteyle ilişkili mekanizmalarını özetlemekte; ayrıca bu organelin terapötik hedef olarak değerlendirilmesi için daha fazla mekanistik ve translasyonel araştırmaya duyulan ihtiyacı vurgulamaktadır.

Anahtar Kelimeler

Primer siliyer , obezite , silyopatiler , enerji homeostazı , hipotalamus

Kaynakça

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