Abstract
Vasoactive Intestinal Peptide binds with high affinity to VPAC1R and VPAC2R, thus regulating key physiologic functions. Previously, we documented in VIP(-/-) mice a leaner body phenotype and altered metabolic hormones. Past reports described in VPAC2(-/-) mice impaired circadian rhythm, reduced food intake, and altered metabolism. To better define the effects of VPAC1R on body phenotype, energy/glucose homeostasis, and metabolism, we conducted a 12-week study in a VPAC1R null model. Our results reveal that VPAC1(-/-) mice experienced significant metabolic alterations during the dark cycle with greater numbers of feeding bouts (p = 0.009), lower Total Energy Expenditure (p = 0.025), VO(2) (p = 0.029), and VCO(2) (p = 0.016); as well as during the light cycle with lower Total Energy Expenditure (p = 0.04), VO(2) (p = 0.044), and VCO(2) (p = 0.029). Furthermore, VPAC1(-/-) mice had significantly higher levels of GLP-1 and PYY during fasting, and higher levels of GLP-1, glucagon leptin and PYY during postprandial conditions. In addition, VPAC1(-/-) mice had lower levels of glucose at 60' and 120', as assessed by insulin tolerance test. In conclusion, this study supports a key role for VPAC1R in the regulation of body glucose/energy homeostasis and metabolism.