Metabolic syndrome and neurometabolic asymmetry of hippocampus in adult bonnet monkeys

ObjectiveObesity is associated with the insulin resistance metabolic syndrome, postulated to be mediated by stress-induced alterations within the hypothalamic-pituitary-adrenal (HPA) axis. In adult bonnet macaques we examined relationships between components of the metabolic syndrome, hippocampal neurometabolic asymmetry, an indicator of negative affect, and juvenile cerebrospinal fluid (csf) corticotropin-releasing factor (CRF) levels obtained after stress exposure associated with maternal food insecurity and in controls.MethodsEleven adult male monkeys (seven with early life stress) who had undergone csf-CRF analyses as juveniles had magnetic resonance spectroscopic imaging (MRSI) of bilateral hippocampus, morphometry (body mass index, BMI; sagittal abdominal diameter, SAD) and determination of fasting plasma glucose and insulin as adults. Neurometabolite ratios included N-acetyl-aspartate as numerator (NAA; a marker of neuronal integrity) and choline (Cho; cell turnover) and creatine (Cr; reference analyte) as denominators.ResultsElevated juvenile csf-CRF levels positively predicted adult BMI and SAD and were associated with right > left shift of NAA ratio within the hippocampus. Adult visceral obesity and insulin level correlated with right > left shift in hippocampal NAA concentrations, controlling for age and denominator.ConclusionJuvenile csf-CRF levels, a neuropeptide associated with early life stress, predict adult visceral obesity and hippocampal asymmetry supporting the hypothesis that metabolic syndrome in adults may be related to early life stress. Furthermore, this study demonstrates asymmetrical hippocampal alterations related to obesity.

Research highlights► Juvenile CRF levels positively predicted adult BMI and sagittal abdominal diameter. ► CRF levels were associated with right > left hippocampal N-acetyl-aspartate (NAA). ► BMI and insulin level correlated with right > left hippocampal NAA concentrations. ► These data associate hippocampal NAA with primate metabolic syndrome. ► Asymmetrical hippocampal alterations are presumably a result of or leading to obesity.