Vu John P, Larauche Muriel, Flores Martin, Luong Leon, Norris Joshua, Oh Suwan, Liang Li-Jung, Waschek James, Pisegna Joseph R, Germano Patrizia M
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.
J Mol Neurosci. 2015 Jun;56(2):377-87. doi: 10.1007/s12031-015-0556-z. Epub 2015 Apr 23.
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.
血管活性肠肽（VIP）是一种由28个氨基酸组成的神经肽，属于促胰液素-胰高血糖素肽超家族，与垂体腺苷酸环化酶激活肽（PACAP）有68%的同源性。VIP在中枢和外周神经系统以及胃肠道中大量表达，在这些部位发挥多种生理功能。此前有报道称，VIP在金鱼、鸡和啮齿动物等不同种类的脊椎动物中对进食行为有中枢调节作用。需要进一步研究来分析内源性VIP在食欲/饱腹感调节、进食行为、代谢激素、身体组成和能量平衡方面的作用。本研究的目的是阐明VIP调节食欲/饱腹感、进食行为、代谢激素和身体组成的生理途径。使用全身成分EchoMRI分析仪，从5周龄到22周龄每周对VIP基因缺陷（VIP -/-）和年龄匹配的野生型（WT）同窝小鼠进行监测。使用BioDAQ自动监测系统分析食物摄入量和进食行为。在空腹和餐后状态下测量包括活性胃饥饿素、胰高血糖素样肽-1（GLP-1）、瘦素、肽YY（PYY）、胰多肽（PP）、脂联素和胰岛素在内的代谢激素的血浆水平。随着小鼠年龄增长，VIP基因的缺失导致体重和脂肪量显著减少，瘦体量增加。此外，VIP -/-小鼠的昼夜进食行为模式紊乱，导致正常的夜间/白天进食规律消失。这些变化与VIP -/-小鼠中脂联素、GLP-1、瘦素、PYY和胰岛素的分泌改变有关。我们的数据表明，内源性VIP参与了食欲/饱腹感、进食行为、身体组成的控制以及六种不同关键调节代谢激素的分泌。VIP通过显著增加体重和脂肪量积累，在身体表型调节中起关键作用。因此，VIP信号传导对于食欲/饱腹感和身体质量表型的调节至关重要，是未来治疗肥胖症的潜在靶点。
