title: Leptin-promoted cilia assembly is critical for normal energy balance.
abstract: 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.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Han
authors.forename: Gil Myoung
authors.initials: GM
authors.lastname: Kang
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Byun
authors.forename: Hyuk Wan
authors.initials: HW
authors.lastname: Ko
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.forename: Mi-Seon
authors.initials: MS
authors.lastname: Shin
authors.forename: Hyun-Kyong
authors.initials: HK
authors.lastname: Kim
authors.forename: So Young
authors.initials: SY
authors.lastname: Gil
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Yu
authors.forename: Bonghee
authors.initials: B
authors.lastname: Lee
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000855:Anorexia / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D020738:Leptin; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism
chemical_list: D007328:Insulin; D020738:Leptin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D005947:Glucose