title: Neuroendocrinological and Epigenetic Mechanisms Subserving Autonomic Imbalance and HPA Dysfunction in the Metabolic Syndrome.
abstract: Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS) has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA) and hypothalamic-pituitary adrenocortical (HPA) axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY)/agouti-related protein systems have been found resulting directly in MetS-like conditions. The review identifies candidate risk genes from factors shown critical for the functioning of each of these neuroendocrine signaling cascades. In its meta-analytic part, recent studies in epigenetic modification (histone methylation, acetylation, phosphorylation, ubiquitination) and posttranscriptional gene regulation by microRNAs are evaluated. Several studies suggest modification mechanisms of early life stress (ELS) and diet-induced obesity (DIO) programming in the hypothalamic regions with populations of POMC-expressing neurons. Epigenetic modifications were found in cortisol (here HSD11B1 expression), melanocortin, leptin, NPY, and adiponectin genes. With respect to adiposity genes, epigenetic modifications were documented for fat mass gene cluster APOA1/C3/A4/A5, and the lipolysis gene LIPE. With regard to inflammatory, immune and subcellular metabolism, PPARG, NKBF1, TNFA, TCF7C2, and those genes expressing cytochrome P450 family enzymes involved in steroidogenesis and in hepatic lipoproteins were documented for epigenetic modifications.
authors.affiliation: Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London London, UK.
authors.forename: Erwin
authors.initials: E
authors.lastname: Lemche
authors.affiliation: Section of Psychosomatic Medicine, Bogomolets National Medical University Kiev, Ukraine.
authors.forename: Oleg S
authors.initials: OS
authors.lastname: Chaban
authors.affiliation: Department of Medical Science, Institute of Clinical Research Berlin, Germany.
authors.forename: Alexandra V
authors.initials: AV
authors.lastname: Lemche
keywords: epigenetic programming; gene regulation; hypothalamic-pituitary adrenocortical axis; metabolic syndrome; microRNA; pathophysiology; stress neuropsychobiology; sympathetic autonomic nervous system