[HTML][HTML] Leptin-promoted cilia assembly is critical for normal energy balance

YM Han, GM Kang, K Byun, HW Ko… - The Journal of …, 2014 - Am Soc Clin Investig
YM Han, GM Kang, K Byun, HW Ko, J Kim, MS Shin, HK Kim, SY Gil, JH Yu, B Lee, MS Kim
The Journal of clinical investigation, 2014Am Soc Clin Investig
The majority of mammalian cells have nonmotile primary cilia on their surface that act as
antenna-like sensory organelles. Genetic defects that result in ciliary dysfunction are
associated with obesity in humans and rodents, which suggests that functional cilia are
important for controlling energy balance. Here we demonstrated that neuronal cilia lengths
were selectively reduced in hypothalami of obese mice with leptin deficiency and leptin
resistance. Treatment of N1 hypothalamic neuron cells with leptin stimulated cilia assembly …
The majority of mammalian cells have nonmotile primary cilia on their surface that act as antenna-like sensory organelles. Genetic defects that result in ciliary dysfunction are associated with obesity in humans and rodents, which suggests that functional cilia are important for controlling energy balance. Here we demonstrated that neuronal cilia lengths were selectively reduced in hypothalami of obese mice with leptin deficiency and leptin resistance. Treatment of N1 hypothalamic neuron cells with leptin stimulated cilia assembly via inhibition of the tumor suppressors PTEN and glycogen synthase kinase 3β (GSK3β). Induction of short cilia in the hypothalamus of adult mice increased food intake and decreased energy expenditure, leading to a positive energy balance. Moreover, mice with short hypothalamic cilia exhibited attenuated anorectic responses to leptin, insulin, and glucose, which indicates that leptin-induced cilia assembly is essential for sensing these satiety signals by hypothalamic neurons. These data suggest that leptin governs the sensitivity of hypothalamic neurons to metabolic signals by controlling the length of the cell’s antenna.
The Journal of Clinical Investigation