Vasoactive Intestinal Polypeptide (VIP) Regulates Metabolic Processes in Human and Murine Adipocytes by Modulating PPARγ Expression
Vasoactive intestinal peptide (VIP) is a neuropeptide expressed centrally in the hypothalamus and peripherally in the GI tract and adipose tissue. VIP and its VPAC receptors regulate body composition, as implicated by pathway-based, genome-wide association studies. We have previously shown that VIP-/- mice have lower fat mass and higher lean mass than their wild-type littermates. To elucidate the role of VIP in fat mass accumulation, VIP-/- mice were fed a 45% high-fat diet for 12 weeks. We determined that VIP-/- mice were resistant to weight gain and fat mass accumulation and had altered feeding behaviors and metabolic hormone levels. VIP antagonism of differentiating pre-adipocytes inhibited induction of adipocyte-related genes, such as PPARγ and C/EBP. Genetic association analyses using data from the METAbolic Syndrome in Men (METSIM) study showed a positive correlation between VIP, VPAC1R and key genetic drivers of adipogenesis. These results implicate VIP’s role in modulating fat accumulation.