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

Abstract

Introduction 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 together with feeding behavior, metabolic hormone release, body mass composition and energy balance. Aims To elucidate the physiological pathways by which VIP regulates appetite/satiety, feeding behavior, metabolic hormones and body mass composition. Methods 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. Results 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. Conclusions Our data show that endogenous VIP is involved in the control of appetite/satiety, feeding behavior, body mass composition and in the secretion of six key regulatory metabolic hormones. VIP plays a key role in the regulation of body weight and mass composition 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 suggested to be a target for future treatment of obesity.

Suprachiasmatic Nucleus Neuropeptides and Their Control of Endogenous Glucose Production

“…VIP‐null mice have elevated fasting and nonfasting glucose and glucagon levels, together with a rise in fasting insulin levels . However, although the SCN is the major production site of VIP within the hypothalamus, the results of the VIP‐null mice provide no evidence for the involvement of SCN VIP in glucose metabolism because VIP has been shown to have clear effects on glucose metabolism both at central and peripheral levels.…”

“…However, despite co-localisaton of both GABA and glutamate with different neuropeptides, also within the SCN (37-41), no conclusive evidence has yet been provided for a role of SCN neuropeptides in the control of daily glucose homeostasis. VIP-null mice have elevated fasting and nonfasting glucose and glucagon levels, together with a rise in fasting insulin levels (42,43). However, although the SCN is the major production site of VIP within the hypothalamus, the results of the VIP-null mice provide no evidence for the involvement of SCN VIP in glucose metabolism because VIP has been shown to have clear effects on glucose metabolism both at central and peripheral levels.…”

Retinoprotective Effects of TAT-Bound Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Polypeptide

“…Among others, PACAP influences gastrointestinal, urinary and cardiovascular functions (Heppner et al 2018 ; Parsons and May 2018 ; Reglodi et al 2018a ), plays a role in reproduction and pregnancy (Lajko et al 2018 ; Reglodi et al 2012 ; Ross et al 2018 ), has diverse behavioral and cognitive functions (Farkas et al 2017 ; Gupta et al 2018 ; Han et al 2014 ; King et al 2017 ), plays roles during both early development and aging (Fulop et al 2018 ; Reglodi et al 2018b ; Watanabe et al 2007 ), as well as influences the functions of both endocrine and exocrine glands (Bardosi et al 2016 ; Egri et al 2016 ; Prevost et al 2013 ; Sasaki et al 2017 ). VIP has also been shown to have diverse actions in addition to the originally described vasodilatory effects (Gozes 2008 ; Hill et al 2007 ; Moody and Gozes 2007 ; Vu et al 2015 ). VIP was originally isolated as a vasoactive peptide in the airways, later confirmed in the gastrointestinal tract (Vu et al 2015 ).…”

Therapeutic effect of vasoactive intestinal peptide on form-deprived amblyopic kittens

“…VIP has also been found to induce glycogen decomposition in the cerebral cortex of mice, potentially through increasing glucose utilization by promoting the formation of AMP [28]. VIP is also involved in regulating the secretion of intracellular pancreatic polypeptide, adiponectin, insulin and other metabolic hormones, thereby affecting cell metabolism [29]. VIP can also activate other excitatory intermediate neurons to produce excitatory postsynaptic potentials, which further increase the excitability of the central nervous system.…”