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.
Various studies link hypertension with anxiety; however, it remains unclarified if such relations are present in the metabolic syndrome (MetS). We studied cross-sectionally the interrelations of self-reported anxiety (Spielberger STAI), and MetS components in MetS patients. We investigated a nationally sampled treatment cohort for MetS with familial Type 2 diabetes risk. N = 101 patients fulfilling International Diabetes Federation criteria for MetS participated. Both laboratory and nonlaboratory measures were included. Structural equation models (SEM) were adjusted. The final SEM had an R(2) = .998 with the obesity component linking to waist, BMI, and degree of adiposity, and the hypertension component linking to systolic blood pressure, pulse pressure, total cholesterol, and trait anxiety. For state anxiety, no significant regressive causal path could be estimated. SEM supports the assumption of an interaction of pulse pressure, systolic blood pressure, cholesterol metabolism, and high trait anxiety in the pathophysiology of hypertension in MetS.
PurposeTriglycerides are considered an emerging risk factor for cardiovascular mortality. Recent evidence relating depression and metabolic syndrome (MetS) implicated triglyceride levels. We thus investigated interrelations of self-reported depression severity (Zung) and MetS-related biological measures with CVD risk estimates in MetS patients.Methods
N = 101 patients fulfilling International Diabetes Federation criteria for MetS from a nationwide sampled treatment cohort for MetS with familial T2DM risk or manifest T2DM in a Ukrainian governmental health care system were participants. Both laboratory and non-laboratory measures were included. Recent European cardiological SCORE system CVD risk estimates were used as outcome variables.ResultsFollowing correlation matrix, we entered all variables into principal component analysis (PCA; 76.7% explained variance), followed by hierarchical regression and structural equation modeling (SEM). The PCA suggested a one-factor solution, where the latent variable showed highest loadings of SCORE risk estimates, triglycerides, depression severity, and pulse pressure. A comprehensive SEM was adjusted with 92.7% explained variance: overall CVD risk related to depression, pulse pressure, triglycerides, and fasting glucose.ConclusionThe findings in this MetS sample suggest that triglycerides and depression severity are the key variables among MetS biomarkers in cross-sectionally associating with the fatal and total SCORE risk estimates in MetS.
Electronic supplementary materialThe online version of this article (doi:10.1007/s40618-016-0601-y) contains supplementary material, which is available to authorized users.
The SEM results suggest that CVD-risk biomarker variables in this MetS sample (a) associate into 2 distinct profiles and (b) that 1 profile associates with overt anger, whereas the other associates with covert hostility. These results could contribute to more personalized prevention and care in CVD patients.
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