Abstract
Obesity is a global health problem that is associated with adverse consequences such as the development of metabolic disorders, including cardiovascular disease, neurodegenerative disorders, and type 2 diabetes. A major cause of obesity is metabolic imbalance, which results from insufficient physical activity and excess energy intake. Understanding the pathogenesis of obesity, as well as other metabolic disorders, is important in the development of methods for prevention and therapy. The coordination of energy balance takes place in the hypothalamus, a major brain region that maintains body homeostasis. The primary cilium is an organelle that has recently received attention because of its role in controlling energy balance in the hypothalamus. Defects in proteins required for ciliary function and formation, both in humans and in mice, have been shown to cause various metabolic disorders. In this review, we provide an overview of the critical functions of primary cilia, particularly in hypothalamic areas, and briefly summarize the studies on the primary roles of cilia in specific neurons relating to metabolic homeostasis.
Highlights
The cilium is a hair-like organelle formed with cell membrane and is present on nearly every mammalian cell
In terms of their formation and functions, cilia are constructed through a microtubule motor-based transport system that consists of intraflagellar transport (IFT) complexes that bind directly to cargos and their motors kinesin-2 and dynein, enabling travel across the axoneme [2, 3]
Specific inhibition of Adenylyl cyclase 3 (ADCY3) through the use of GPR88, a constitutively active version of the cilia-specific Gαi-protein-coupled receptor, resulted in suppression of cyclic AMP (cAMP) production and, increased body weight. These findings suggest that MC4R and ADCY3 may positively regulate cAMP generation in neuronal primary cilia of the paraventricular nucleus (PVN), where MC4R is highly expressed, and impaired cAMP signaling in the primary cilia of MC4R-expressing neurons leads to obesity
Summary
The cilium is a hair-like organelle formed with cell membrane and is present on nearly every mammalian cell. The axoneme emerges from the basal body, a centriole-derived and microtubule-organizing center, extending from the cell surface into the extracellular space [1] In terms of their formation and functions, cilia are constructed through a microtubule motor-based transport system that consists of intraflagellar transport (IFT) complexes that bind directly to cargos and their motors kinesin-2 and dynein, enabling travel across the axoneme [2, 3]. The medical significance of primary cilia, beyond their relation to PKD, became increasingly evident, with evidence showing that the structural and functional anomalies of primary cilia arise from genetic mutations in ciliary proteins These proteins are closely related to human diseases comprehensively called ciliopathies, including retinal degeneration, polydactyly, hypertension, and obesity [6]. In this review, we summarize the evidence supporting the role of hypothalamic primary cilia in controlling metabolic homeostasis
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