The VIP/VPAC1R Pathway Regulates Energy and Glucose Homeostasis by Modulating GLP-1, Glucagon, Leptin and PYY Levels in Mice.

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 ( = 0.009), lower Total Energy Expenditure ( = 0.025), VO ( = 0.029), and VCO ( = 0.016); as well as during the light cycle with lower Total Energy Expenditure ( = 0.04), VO ( = 0.044), and VCO ( = 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.