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Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP)

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Abstract

Vasoactive intestinal peptide (VIP) is a 28-amino acid neuropeptide that belongs to the secretin-glucagon superfamily of peptides and has 68 % homology with PACAP. VIP is abundantly expressed in the central and peripheral nervous system and in the gastrointestinal tract, where it exercises several physiological functions. Previously, it has been reported that VIP regulates feeding behavior centrally in different species of vertebrates such as goldfishes, chicken and rodents. Additional studies are necessary to analyze the role of endogenous VIP on the regulation of appetite/satiety, feeding behavior, metabolic hormones, body mass composition and energy balance. The aim of the study was to elucidate the physiological pathways by which VIP regulates appetite/satiety, feeding behavior, metabolic hormones, and body mass composition. VIP deficient (VIP −/−) and age-matched wild-type (WT) littermates were weekly monitored from 5 to 22 weeks of age using a whole body composition EchoMRI analyzer. Food intake and feeding behavior were analyzed using the BioDAQ automated monitoring system. Plasma levels of metabolic hormones including active-ghrelin, GLP-1, leptin, PYY, pancreatic polypeptide (PP), adiponectin, and insulin were measured in fasting as well as in postprandial conditions. The genetic lack of VIP led to a significant reduction of body weight and fat mass and to an increase of lean mass as the mice aged. Additionally, VIP−/− mice had a disrupted pattern of circadian feeding behavior resulting in an abolished regular nocturnal/diurnal feeding. These changes were associated with an altered secretion of adiponectin, GLP-1, leptin, PYY and insulin in VIP−/− mice. Our data demonstrates that endogenous VIP is involved in the control of appetite/satiety, feeding behavior, body mass composition and in the secretion of six different key regulatory metabolic hormones. VIP plays a key role in the regulation of body phenotype by significantly enhancing body weight and fat mass accumulation. Therefore, VIP signaling is critical for the modulation of appetite/satiety and body mass phenotype and is a potential target for future treatment of obesity.

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Acknowledgments

This work received grant support from: Department of Veterans Affairs RR&D Merit Review (JRP); Department of Veterans Affairs RR&D Merit Review (PMG); NIH K01 DK088937 (ML); and Animal Core Services performed through CURE: Digestive Disease Research Center supported by NIH grant P30DK41301.

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Authors and Affiliations

  1. CURE/Digestive Diseases Research Center, Department of Medicine at the University of California at Los Angeles, & VA Greater Los Angeles Health Care System, Los Angeles, CA, USA

    John P. Vu, Muriel Larauche, Leon Luong, Joshua Norris, Suwan Oh, Joseph R. Pisegna & Patrizia M. Germano

  2. Department of Biostatistics, School of Public Health, University of California at Los Angeles, Los Angeles, CA, USA

    Martin Flores

  3. Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    Li-Jung Liang

  4. Department of Psychiatry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    James Waschek

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  1. John P. Vu
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  10. Patrizia M. Germano
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Correspondence to Patrizia M. Germano.

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Vu, J.P., Larauche, M., Flores, M. et al. Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP). J Mol Neurosci 56, 377–387 (2015). https://doi.org/10.1007/s12031-015-0556-z

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