Role of neuropeptide Y in diet-, chemical- and genetic-induced obesity of mice.
OBJECTIVE
The goal of this study was to ascertain whether neuropeptide Y (NPY) is required in mice for the development of obesity induced by a high-fat diet (HFD), chemical lesions of the hypothalamus caused by monosodium glutamate (MSG) or gold thioglucose (GTG), impaired brown adipose tissue (BAT) due to a diphtheria toxin transgene driven by the uncoupling protein 1 promoter (UCP-DTA) or the lethal yellow agouti mutation (Ay).


BACKGROUND
The obesity syndrome of the leptin-deficient (ob/ob) mouse can be partially reversed by the genetic removal of NPY. In the murine models of obesity examined in this study, the animals become obese despite increased serum leptin levels, indicating that they are resistant to the weight-limiting actions of leptin. The role of NPY in these obesity models with elevated leptin levels is unknown.


METHODS
Mice lacking NPY due to genetic disruption of the gene and wildtype littermates were made obese by allowing them access to a highly palatable HFD, by treatment with MSG, or GTG, or by inheriting the dominant UCP-DTA or Ay alleles. Food consumption, body weight and dissectable fat pad weights were measured and compared to values obtained from non-obese littermates.


RESULTS
In each model of obesity tested, NPY-deficient mice achieved the same food intake, body weight and fat content as wildtype littermates.


CONCLUSIONS
NPY is not necessary for the progressive development of obesity exhibited by multiple murine models with leptin resistance.
Hollopeter
G
G
Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle 98195, USA.
Erickson
J C
JC
Palmiter
R D
RD
D002001:Adipose Tissue, Brown / Q000503:physiopathology; D054366:Agouti Signaling Protein; D000818:Animals; D006051:Aurothioglucose; D001823:Body Composition; D001835:Body Weight; D002352:Carrier Proteins / Q000235:genetics; D004032:Diet; D004167:Diphtheria Toxin / Q000235:genetics; D004435:Eating; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D020738:Leptin; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins; D009154:Mutation; D009478:Neuropeptide Y / Q000502:physiology*; D009765:Obesity / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012970:Sodium Glutamate; D000071256:Uncoupling Protein 1
D054366:Agouti Signaling Protein; D002352:Carrier Proteins; D004167:Diphtheria Toxin; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D011506:Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D006051:Aurothioglucose; D012970:Sodium Glutamate