Oh Edwin C, Vasanth Shivakumar, Katsanis Nicholas
Center for Human Disease Modeling, Duke University School of Medicine, Durham, NC 27710, USA.
Center for Human Disease Modeling, Duke University School of Medicine, Durham, NC 27710, USA.
Cell Metab. 2015 Jan 6;21(1):21-31. doi: 10.1016/j.cmet.2014.11.019. Epub 2014 Dec 24.
Obesity and diabetes represent a significant healthcare concern. In contrast to genome-wide association studies that, some exceptions notwithstanding, have offered modest clues about pathomechanism, the dissection of rare disorders in which obesity represents a core feature have highlighted key molecules and structures critical to energy regulation. Here we focus on the primary cilium, an organelle whose roles in energy homeostasis have been underscored by the high incidence of obesity and type II diabetes in patients and mouse mutants with compromised ciliary function. We discuss recent evidence linking ciliary dysfunction to metabolic defects and we explore the contribution of neuronal and nonneuronal cilia to these phenotypes.
肥胖和糖尿病是重大的医疗保健问题。全基因组关联研究虽然有一些例外情况,但仅提供了关于发病机制的有限线索,而对以肥胖为核心特征的罕见疾病的剖析则突出了对能量调节至关重要的关键分子和结构。在这里,我们聚焦于初级纤毛,这是一种细胞器,在纤毛功能受损的患者和小鼠突变体中,肥胖和II型糖尿病的高发病率凸显了其在能量稳态中的作用。我们讨论了将纤毛功能障碍与代谢缺陷联系起来的最新证据,并探讨了神经元和非神经元纤毛对这些表型的影响。