title: Neuromedin U receptor 2 knockdown in the paraventricular nucleus modifies behavioral responses to obesogenic high-fat food and leads to increased body weight.
abstract: Neuromedin U (NMU) is a highly conserved neuropeptide which regulates food intake and body weight. Transgenic mice lacking NMU are hyperphagic and obese, making NMU a novel target for understanding and treating obesity. Neuromedin U receptor 2 (NMUR2) is a high-affinity receptor for NMU found in discrete regions of the central nervous system, in particular the paraventricular nucleus of the hypothalamus (PVN), where it may be responsible for mediating the anorectic effects of NMU. We hypothesized that selective knock down of NMUR2 in the PVN of rats would increase their sensitivity to the reinforcing properties of food resulting in increased intake and preference for high-fat obesogenic food. To this end, we used viral-mediated RNAi to selectively knock down NMUR2 gene expression in the PVN. In rats fed a standard chow, NMUR2 knockdown produced no significant effect on food intake or body weight. However, when the same rats were fed a high-fat diet (45% fat), they consumed significantly more food, gained more body weight, and had increased feed efficiency relative to controls. Furthermore, NMUR2 knockdown rats demonstrated significantly greater binge-type food consumption of the high-fat diet and showed a greater preference for higher-fat food. These results demonstrate that NMUR2 signaling in the PVN regulates consumption and preference for high-fat foods without disrupting feeding behavior associated with non-obesogenic standard chow.
authors.affiliation: Center for Addiction Research, Department of Pharmacology & Toxicology, University of Texas Medical Branch, United States.
authors.forename: C R
authors.initials: CR
authors.lastname: Benzon
authors.affiliation: Center for Addiction Research, Department of Pharmacology & Toxicology, University of Texas Medical Branch, United States.
authors.forename: S B
authors.initials: SB
authors.lastname: Johnson
authors.affiliation: Center for Addiction Research, Department of Pharmacology & Toxicology, University of Texas Medical Branch, United States.
authors.forename: D L
authors.initials: DL
authors.lastname: McCue
authors.affiliation: Center for Addiction Research, Department of Pharmacology & Toxicology, University of Texas Medical Branch, United States.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.affiliation: Center for Addiction Research, Department of Pharmacology & Toxicology, University of Texas Medical Branch, United States.
authors.forename: T A
authors.initials: TA
authors.lastname: Green
authors.affiliation: Center for Addiction Research, Department of Pharmacology & Toxicology, University of Texas Medical Branch, United States. Electronic address: jdhommel@utmb.edu.
authors.forename: J D
authors.initials: JD
authors.lastname: Hommel
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D059305:Diet, High-Fat; D004041:Dietary Fats; D004435:Eating; D005247:Feeding Behavior / Q000502:physiology*; D005518:Food Preferences / Q000502:physiology; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*; D012054:Reinforcement, Psychology; D013395:Sucrose; D015430:Weight Gain / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D034741:RNA, Small Interfering; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; D013395:Sucrose
keywords: 4’,6-diamidino-2-phenylindole; AAV; DAPI; GFP; NMU; NMUR2; PVN; RO; adeno-associated virus; binge eating; dietary fat; feeding behavior; green fluorescent protein; neuromedin U; neuromedin U receptor 2; obesity; paraventricular nucleus; reverse osmosis; shCTRL; shNMUR2; shRNA; small hairpin NMUR2 knockdown RNA; small hairpin RNA; small hairpin control (non-silencing) RNA; viral RNA interference