Research Article Glucagon-Like Peptide-1 as Predictor of Body Mass Index and Dentate Gyrus Neurogenesis: Neuroplasticity and the Metabolic Milieu Jeremy D. Coplan, 1 Shariful Syed, 2 Tarique D. Perera, 3 Sasha L. Fulton, 3 Mary Ann Banerji, 4 Andrew J. Dwork, 5,6 and John G. Kral 7 1 Department of Psychiatry & Behavioral Sciences, Division of Neuropsychopharmacology, State University of New York, Downstate Medical Center (SUNY DMC), Brooklyn, NY 11203, USA 2 Downstate College of Medicine, SUNY DMC, Brooklyn, NY 11203, USA 3 New York State Psychiatric Institute, New York, NY 10032, USA 4 Division of Endocrinology, Department of Internal Medicine, SUNY DMC, Brooklyn, NY 11203, USA 5 Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY 10032, USA 6 Departments of Psychiatry and Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA 7 Departments of Surgery and Internal Medicine, SUNY DMC, Brooklyn, NY 11203, USA Correspondence should be addressed to Jeremy D. Coplan; copstat00@aol.com Received 5 July 2014; Revised 14 October 2014; Accepted 15 October 2014; Published 23 November 2014 Academic Editor: Lucas Pozzo-Miller Copyright © 2014 Jeremy D. Coplan et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Glucagon-like peptide-1 (GLP-1) regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1), and body mass index (BMI) in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing efects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively refect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues. 1. Introduction Te precedent for a relationship between metabolic processes and neuroprotection is ontogenetically evident in the inver- tebrate, C. elegans, involving DAF2-mediated gene expres- sion, a homolog of mammalian insulin receptor expres- sion [1]. DAF-2 tightly regulates fatty acid and amino acid metabolism [2]. In light of the evolutionary conservation of the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway, studies extrapolated from C. elegans shed light on its functions and regulation in higher organisms, including nonhuman primates and humans [3]. For instance, downregulation of the insulin/IGF-1 signaling pathway has been demonstrated to induce diapause in C. elegans, a state associated with neuronal loss [4]. GLP-1 is an insulinotropic incretin produced by enteroen- docrine L cells found throughout the small intestine [5]. GLP- 1 and its receptor system have been shown to afect central Hindawi Publishing Corporation Neural Plasticity Volume 2014, Article ID 917981, 10 pages http://dx.doi.org/10.1155/2014/917981