title: An obligate role of oxytocin neurons in diet induced energy expenditure.
abstract: Oxytocin neurons represent one of the major subsets of neurons in the paraventricular hypothalamus (PVH), a critical brain region for energy homeostasis. Despite substantial evidence supporting a role of oxytocin in body weight regulation, it remains controversial whether oxytocin neurons directly regulate body weight homeostasis, feeding or energy expenditure. Pharmacologic doses of oxytocin suppress feeding through a proposed melanocortin responsive projection from the PVH to the hindbrain. In contrast, deficiency in oxytocin or its receptor leads to reduced energy expenditure without feeding abnormalities. To test the physiological function of oxytocin neurons, we specifically ablated oxytocin neurons in adult mice. Our results show that oxytocin neuron ablation in adult animals has no effect on body weight, food intake or energy expenditure on a regular diet. Interestingly, male mice lacking oxytocin neurons are more sensitive to high fat diet-induced obesity due solely to reduced energy expenditure. In addition, despite a normal food intake, these mice exhibit a blunted food intake response to leptin administration. Thus, our study suggests that oxytocin neurons are required to resist the obesity associated with a high fat diet; but their role in feeding is permissive and can be compensated for by redundant pathways.
authors.affiliation: Brown Foundation Institute of Molecular Medicine, University of Texas Medical School at Houston, Houston, Texas, USA.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Wu
authors.forename: Yuanzhong
authors.initials: Y
authors.lastname: Xu
authors.forename: Yaming
authors.initials: Y
authors.lastname: Zhu
authors.forename: Amy K
authors.initials: AK
authors.lastname: Sutton
authors.forename: Rongjie
authors.initials: R
authors.lastname: Zhao
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.forename: David P
authors.initials: DP
authors.lastname: Olson
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Tong
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis; D007274:Injections, Intraperitoneal; D020738:Leptin / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism* / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D020738:Leptin; D010121:Oxytocin