Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA.
Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University, Indianapolis, IN, USA; Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, USA.
Semin Cell Dev Biol. 2021 Feb;110:43-50. doi: 10.1016/j.semcdb.2020.05.006. Epub 2020 May 25.
An emerging number of rare genetic disorders termed ciliopathies are associated with pediatric obesity. It is becoming clear that the mechanisms associated with cilia dysfunction and obesity in these syndromes are complex. In addition to ciliopathic syndromic forms of obesity, several cilia-associated signaling gene mutations also lead to morbid obesity. While cilia have critical and diverse functions in energy homeostasis including their roles in centrally mediated food intake as well as in peripheral tissues, many questions remain. Here, we briefly discuss the syndromic ciliopathies and monoallelic cilia signaling gene mutations associated with obesity. We also describe potential ways cilia may be involved in common obesity. We discuss how neuronal cilia impact food intake potentially through leptin signaling and changes in ciliary G protein-coupled receptor (GPCR) signaling. We highlight several recent studies that have implicated the potential for cilia in peripheral tissues such as adipose and the pancreas to contribute to metabolic dysfunction. Then we discuss the potential for cilia to impact energy homeostasis through their roles in both development and adult tissue homeostasis. The studies discussed in this review highlight how a comprehensive understanding of the requirement of cilia for the regulation of diverse biological functions will contribute to our understanding of common forms of obesity.
越来越多的罕见遗传性疾病被称为纤毛病，与小儿肥胖有关。目前已经清楚，这些综合征中与纤毛功能障碍和肥胖相关的机制非常复杂。除了纤毛病的肥胖综合征形式外，几种与纤毛相关的信号基因突变也会导致严重肥胖。虽然纤毛在能量平衡中具有关键而多样的功能，包括在中枢介导的食物摄入以及外周组织中的作用，但仍有许多问题尚未解决。在这里，我们简要讨论与肥胖相关的综合征性纤毛病和单等位基因纤毛信号基因突变。我们还描述了纤毛可能参与常见肥胖的潜在方式。我们讨论了神经元纤毛如何通过瘦素信号和纤毛 G 蛋白偶联受体 (GPCR) 信号的变化来影响食物摄入。我们强调了几项最近的研究，这些研究表明纤毛在外周组织（如脂肪组织和胰腺）中可能发挥作用，导致代谢功能障碍。然后，我们讨论了纤毛通过在发育和成人组织稳态中的作用来影响能量平衡的潜力。本文讨论的研究强调了全面了解纤毛对调节多种生物学功能的要求将有助于我们理解常见肥胖形式。
