title: Neuropeptide Y and peptide YY protect from weight loss caused by Bacille Calmette-Guérin in mice.
abstract: OBJECTIVE
  Immune challenge of mice with Bacille Calmette-Guérin (BCG) has been reported to cause transient weight loss and a behavioural sickness response. Although BCG-induced depression involves the kynurenine pathway, weight loss occurs independently of this factor. Because neuropeptide Y (NPY) and peptide YY (PYY) are involved in the regulation of food intake, we hypothesized that they play a role in the BCG-induced weight loss.
  
  
  METHODS
  Male wild-type, PYY knockout (PYY-/-), NPY knockout (NPY-/-) and NPY-/-;PYY-/- double knockout mice were injected with vehicle or BCG (approximately 10(8) colony-forming units per mouse), and their weight, locomotion, exploration and ingestion were recorded for 2 weeks post-treatment.
  
  
  RESULTS
  Deletion of PYY and NPY aggravated the BCG-induced loss of body weight, which was most pronounced in NPY-/-;PYY-/- mice (maximum loss: 15%). The weight loss in NPY-/-;PYY-/- mice did not normalize during the 2 week observation period. BCG suppressed the circadian pattern of locomotion, exploration and food intake. However, these changes took a different time course than the prolonged weight loss caused by BCG in NPY-/-;PYY-/- mice. The effect of BCG to increase circulating IL-6 (measured 16 days post-treatment) remained unaltered by knockout of PYY, NPY or NPY plus PYY.
  
  
  CONCLUSIONS
  These data show that NPY and PYY are both required to protect from the action of BCG-evoked immune challenge to cause prolonged weight loss and disturb energy balance. The findings attest to an important role of NPY and PYY in orchestrating homeostatic reactions to infection and immune stimulation.
authors.affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
authors.forename: Evelin
authors.initials: E
authors.lastname: Painsipp
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Köfer
authors.forename: Aitak
authors.initials: A
authors.lastname: Farzi
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Dischinger
authors.forename: Frank
authors.initials: F
authors.lastname: Sinner
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Peter
authors.initials: P
authors.lastname: Holzer
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009478:Neuropeptide Y / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019894:Peptide YY / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects*
chemical_list: C087507:BCG Connaught; D001500:BCG Vaccine; D015850:Interleukin-6; D009478:Neuropeptide Y; C577686:interleukin-6, mouse; D019894:Peptide YY; D003345:Corticosterone
keywords: Bacille Calmette-Guérin; IL-6; corticosterone; exploration; food intake; immune stimulation; locomotion; neuropeptide Y; peptide YY; sickness behaviour