Discrete BDNF Neurons in the Paraventricular Hypothalamus Control Feeding and Energy Expenditure

• Published in: Cell metabolism 2015-07, Vol.22 (1), p.175-188
• Main Authors: An, Juan Ji, Liao, Guey-Ying, Kinney, Clint E., Sahibzada, Niaz, Xu, Baoji
• Format: Article
• Language: English
• Subjects: Animals; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Energy Metabolism; Feeding Behavior; Female; Gene Deletion; Hyperphagia - genetics; Hyperphagia - metabolism; Hyperphagia - pathology; Hypothalamus - cytology; Hypothalamus - pathology; Hypothalamus - physiology; Locomotion; Male; Mice; Mice, Inbred C57BL; Neurons - metabolism; Neurons - pathology; Thermogenesis
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2015.05.008

Brain-derived neurotrophic factor (BDNF) is a key regulator of energy balance; however, its underlying mechanism remains unknown. By analyzing BDNF-expressing neurons in paraventricular hypothalamus (PVH), we have uncovered neural circuits that control energy balance. The Bdnf gene in the PVH was mostly expressed in previously undefined neurons, and its deletion caused hyperphagia, reduced locomotor activity, impaired thermogenesis, and severe obesity. Hyperphagia and reduced locomotor activity were associated with Bdnf deletion in anterior PVH, whereas BDNF neurons in medial and posterior PVH drive thermogenesis by projecting to spinal cord and forming polysynaptic connections to brown adipose tissues. Furthermore, BDNF expression in the PVH was increased in response to cold exposure, and its ablation caused atrophy of sympathetic preganglionic neurons. Thus, BDNF neurons in anterior PVH control energy intake and locomotor activity, whereas those in medial and posterior PVH promote thermogenesis by releasing BDNF into spinal cord to boost sympathetic outflow. [Display omitted] •The PVH is a key structure that produces BDNF to control energy balance•The majority of BDNF neurons in the PVH are distinct from previously defined ones•BDNF neurons in the anterior PVH inhibit feeding and stimulate locomotor activity•BDNF neurons in the medial and posterior PVH drive adaptive thermogenesis Distinct subsets of BDNF-expressing neurons in the paraventricular hypothalamus (PVH) control different aspects of energy balance, with those in the anterior PVH suppressing food intake and promoting locomotor activity and those in the medial and posterior PVH driving adaptive thermogenesis through polysynaptic connections to brown adipose tissues.