Glucagon-Like Peptide-1 as Predictor of Body Mass Index and Dentate Gyrus Neurogenesis: Neuroplasticity and the Metabolic Milieu

Abstract

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 profiles 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 effects 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 reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues.

Patterns of anterior versus posterior white matter fractional anistotropy concordance in adult nonhuman primates: Effects of early life stress

“…The primary analysis of the DTI data has been published (23) and the current report comprises a secondary analysis. Data on neurogenesis rates (52), hippocampal volume (16) and amygdala volume (22) have been reported on previously in the identical cohort.…”

“…Details for these measurements have been described previously (16, 22, 52). Dentate gyrus neurogenesis was measured at a mean age of 8.7 years whereas volumetric measurements were obtained concomitant to the DTI data (see Table 1).…”

Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration

“…In addition to inducing the expression of growth factors such as Brain‐Derived Neurotrophic Factor (BDNF), which promote neuronal survival (Spielman, Gibson, & Klegeris, ), likewise, it has been observed that incretins prevent neuronal death, and reduce oxidative stress in animals injected with drugs that induce excitotoxicity in the brain (Koshal & Kumar, ). Incretins treatment promotes synaptic plasticity by increasing the number of dendritic spines in regions such as the hippocampus (Coplan et al, ). It also reduces Aβ levels and improves spatial memory.…”

Factors that influence adult neurogenesis as potential therapy

“…Furthermore, the 8 week administration of liraglutide, an analog of the incretin hormone glucagon-like peptide-1, prevented the decline in hippocampal neurogenesis in a mouse model of AD [ 152 ]. Non-human primates with low body mass index and high GLP-1 levels also tend to have higher hippocampal neurogenesis in comparison to those with high body mass index and low GLP-1 levels [ 153 ]. These studies highlight metabolic hormone influences on adult hippocampal neurogenesis.…”