BackgroundNAFLD progression, from steatosis to inflammation and fibrosis, results from an interplay of intra- and extrahepatic mechanisms. Disease drivers likely include signals from white adipose... Show moreBackgroundNAFLD progression, from steatosis to inflammation and fibrosis, results from an interplay of intra- and extrahepatic mechanisms. Disease drivers likely include signals from white adipose tissue (WAT) and gut. However, the temporal dynamics of disease development remain poorly understood.MethodsHigh-fat-diet (HFD)-fed Ldlr−/−.Leiden mice were compared to chow-fed controls. At t = 0, 8, 16, 28 and 38w mice were euthanized, and liver, WAT depots and gut were analyzed biochemically, histologically and by lipidomics and transcriptomics together with circulating factors to investigate the sequence of pathogenic events and organ cross-talk during NAFLD development.ResultsHFD-induced obesity was associated with an increase in visceral fat, plasma lipids and hyperinsulinemia at t = 8w, along with increased liver steatosis and circulating liver damage biomarkers. In parallel, upstream regulator analysis predicted that lipid catabolism regulators were deactivated and lipid synthesis regulators were activated. Subsequently, hepatocyte hypertrophy, oxidative stress and hepatic inflammation developed. Hepatic collagen accumulated from t = 16 w and became pronounced at t = 28–38 w. Epididymal WAT was maximally hypertrophic from t = 8 w, which coincided with inflammation development. Mesenteric and subcutaneous WAT hypertrophy developed slower and did not appear to reach a maximum, with minimal inflammation. In gut, HFD significantly increased permeability, induced a shift in microbiota composition from t = 8 w and changed circulating gut-derived metabolites.ConclusionHFD-fed Ldlr−/−.Leiden mice develop obesity, dyslipidemia and insulin resistance, essentially as observed in obese NAFLD patients, underlining their translational value. We demonstrate that marked epididymal-WAT inflammation, and gut permeability and dysbiosis precede the development of NAFLD stressing the importance of a multiple-organ approach in the prevention and treatment of NAFLD. Show less
The Levels of Emotional Awareness Scale (LEAS) is a well-validated performance measure of trait emotional awareness (EA), which is associated with psychological and physical problems. EA is,... Show moreThe Levels of Emotional Awareness Scale (LEAS) is a well-validated performance measure of trait emotional awareness (EA), which is associated with psychological and physical problems. EA is, however, expected to vary over time and we aimed to adapt the LEAS to permit the measurement of EA in daily life as a function of momentary state. Twenty-five students completed 12 ecological momentary assessments (EMAs) of EA across 2 days. The correlation between the mean EMAs of EA and trait EA, and the change over time in EA, was also examined. Findings revealed a significant positive correlation between state and trait EA. The within-person reliability was substantial, suggesting that EMAs can reliably assess EA over time across individuals. Importantly, latent state-trait analysis showed that about 50% of EA variability was due to state variance whereas only 2% of EA variability was due to trait variance. Preliminary psychometric properties suggest that the developed method allows for the measurement of EA in daily life and supports the claim that EA can be measured using both hypothetical (as in the LEAS) and real-life (using EMAs) scenarios. Show less
