Abstract
The primary cilium, an antenna-like structure on most eukaryotic cells, functions in transducing extracellular signals into intracellular responses via the receptors and ion channels distributed along it membrane. Dysfunction of this organelle causes an array of human diseases, known as ciliopathies, that often feature obesity and diabetes; this indicates the primary cilia’s active role in energy metabolism, which it controls mainly through hypothalamic neurons, preadipocytes, and pancreatic β-cells. The nutrient sensor, O-GlcNAc, is widely involved in the regulation of energy homeostasis. Not only does O-GlcNAc regulate ciliary length, but it also modifies many components of cilia-mediated metabolic signaling pathways. Therefore, it is likely that O-GlcNAcylation (OGN) plays an important role in regulating energy homeostasis in primary cilia. Abnormal OGN, as seen in cases of obesity and diabetes, may play an important role in primary cilia dysfunction mediated by these pathologies.
Highlights
Dysregulation of energy metabolism is a major cause of obesity [18]; obesity is associated with insulin resistance and type 2 diabetes mellitus (T2DM) [19,20]
Considering escalated OGN levels are tightly correlated with diabetes and glucose availability [54,55], these findings suggest a potential role of O-GlcNAc in primary ciliary length regulation
Mice lacking cilia in adulthood become obese and display elevated serum leptin, insulin, and glucose levels [26]. These results indicate that the role of primary cilia on neurons in the hypothalamus in response to satiety signals, such as leptin and insulin, is to regulate energy homeostasis [26,61,71]
Summary
Primary cilia were first discovered in 1898 and given this name by Sergei Sorokin in 1968 [1,2]. They were considered vestigial organelles until recent research revealed their presence on most types of quiescent mammalian cells, including neurons, pancreatic endocrine cells, respiratory tract cells, and smooth muscles [2,3,4,5]. Primary cilia are composed of a nine-doublet microtubule (DMT)-based axoneme enclosed by a highly modified ciliary membrane [6]. Ciliopathies usually coincide with obesity, diabetes, metabolic disorder, cancer, and neurodegenerative diseases, suggesting that the functions of primary cilia include metabolic regulation and maintenance of energy homeostasis [17]. Functions of primary cilia in regulating energy homeostasis have been widely studied in the mouse model system as well as in humans and are described in the following three aspects
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