Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus.
The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing cell types that comprise a major autonomic output nucleus and play critical roles in the control of food intake and energy homeostasis. The roles of specific PVH neuronal subtypes in energy balance have yet to be defined, however. The PVH contains nitric oxide synthase-1 (Nos1)-expressing (Nos1(PVH)) neurons of unknown function; these represent a subset of the larger population of Sim1-expressing PVH (Sim1(PVH)) neurons. To determine the role of Nos1(PVH) neurons in energy balance, we used Cre-dependent viral vectors to both map their efferent projections and test their functional output in mice. Here we show that Nos1(PVH) neurons project to hindbrain and spinal cord regions important for food intake and energy expenditure control. Moreover, pharmacogenetic activation of Nos1(PVH) neurons suppresses feeding to a similar extent as Sim1(PVH) neurons, and increases energy expenditure and activity. Furthermore, we found that oxytocin-expressing PVH neurons (OXT(PVH)) are a subset of Nos1(PVH) neurons. OXT(PVH) cells project to preganglionic, sympathetic neurons in the thoracic spinal cord and increase energy expenditure upon activation, though not to the same extent as Nos1(PVH) neurons; their activation fails to alter feeding, however. Thus, Nos1(PVH) neurons promote negative energy balance through changes in feeding and energy expenditure, whereas OXT(PVH) neurons regulate energy expenditure alone, suggesting a crucial role for non-OXT Nos1(PVH) neurons in feeding regulation.
Department of Molecular & Integrative Physiology.
Amy K
AK
Sutton
Division of Division of Pediatric Endocrinology, Department of Pediatrics & Communicable Diseases, and.
Hongjuan
H
Pei
Division of Division of Pediatric Endocrinology, Department of Pediatrics & Communicable Diseases, and.
Korri H
KH
Burnett
Department of Molecular & Integrative Physiology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan 48109, and.
Martin G
MG
Myers
Department of Internal Medicine, University of Chicago, Chicago, Illinois 60637.
Christopher J
CJ
Rhodes
Division of Division of Pediatric Endocrinology, Department of Pediatrics & Communicable Diseases, and dpolson@med.umich.edu.
David P
DP
Olson
D000818:Animals; D001069:Appetite Regulation / Q000235:genetics / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000502:physiology*; D010121:Oxytocin / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000033:anatomy & histology / Q000166:cytology* / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology; D012249:Rhombencephalon / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology; D013116:Spinal Cord / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D052248:Nitric Oxide Synthase Type I; D010121:Oxytocin; D012097:Repressor Proteins; C101750:Sim1 protein, mouse; C496321:Nos1 protein, mouse
body weight; energy balance; hypothalamus; oxygen consumption; oxytocin; satiety