RGD Reference Report - Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice. - Rat Genome Database

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Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice.

Authors: Kushi, A  Sasai, H  Koizumi, H  Takeda, N  Yokoyama, M  Nakamura, M 
Citation: Kushi A, etal., Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15659-64.
RGD ID: 1642306
Pubmed: PMID:9861026   (View Abstract at PubMed)
PMCID: PMC28100   (View Article at PubMed Central)

To elucidate the role of neuropeptide Y (NPY)-Y1 receptor (Y1-R) in food intake, energy expenditure, and other possible functions, we have generated Y1-R-deficient mice (Y1-R-/-) by gene targeting. Contrary to our hypothesis that the lack of NPY signaling via Y1-R would result in impaired feeding and weight loss, Y1-R-/- mice showed a moderate obesity and mild hyperinsulinemia without hyperphagia. Although there was some variation between males and females, typical characteristics of Y1-R-/- mice include: greater body weight (females more than males), an increase in the weight of white adipose tissue (WAT) (approximately 4-fold in females), an elevated basal level of plasma insulin (approximately 2-fold), impaired insulin secretion in response to glucose administration, and a significant changes in mitochondrial uncoupling protein (UCP) gene expression (up-regulation of UCP1 in brown adipose tissue and down-regulation of UCP2 in WAT). These results suggest either that the Y1-R in the hypothalamus is not a key molecule in the leptin/NPY pathway, which controls feeding behavior, or that its deficiency is compensated by other receptors, such as NPY-Y5 receptor. We believe that the mild obesity found in Y1-R-/- mice (especially females) was caused by the impaired control of insulin secretion and/or low energy expenditure, including the lowered expression of UCP2 in WAT. This model will be useful for studying the mechanism of mild obesity and abnormal insulin metabolism in noninsulin-dependent diabetes mellitus.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NPY1RHumanobesity susceptibilityISONpy1r (Mus musculus)associated with HyperinsulinemiaRGD 
Npy1rRatobesity susceptibilityISONpy1r (Mus musculus)associated with HyperinsulinemiaRGD 
Npy1rMouseobesity susceptibilityIAGP associated with HyperinsulinemiaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Npy1r  (neuropeptide Y receptor Y1)

Genes (Mus musculus)
Npy1r  (neuropeptide Y receptor Y1)

Genes (Homo sapiens)
NPY1R  (neuropeptide Y receptor Y1)


Additional Information