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

Abstract

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.

• Authors: A Kushi, H Sasai, H Koizumi, N Takeda, M Yokoyama, M Nakamura
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 95 Issue 26 Pg. 15659-64 (Dec 22 1998) ISSN: 0027-8424 [Print] United States
• PMID: 9861026 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Receptors, Neuropeptide Y
• neuropeptide Y-Y1 receptor

Topics

• Animals
• Blood Glucose (metabolism)
• Body Temperature
• Body Weight
• Cardiopulmonary Resuscitation
• Chimera
• Feeding Behavior
• Female
• Genomic Library
• Glucose Tolerance Test
• Hyperinsulinism (genetics)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred Strains
• Mice, Knockout
• Obesity (genetics, physiopathology)
• Receptors, Neuropeptide Y (deficiency, genetics, physiology)
• Sex Characteristics