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Background: Obesity and the related entity metabolic syndrome are characterized by altered lipid metabolism and associated with increased morbidity risk for cardiovascular disease and cancer. Oxysterols belong to a large family of cholesterol-derived molecules known to play crucial role in many signaling pathways underlying several diseases. Little is known on the potential effect of obesity and metabolic syndrome on oxysterols in human., Objectives: In this work, we questioned whether circulating oxysterols might be significantly altered in obese patients and in patients with metabolic syndrome. We also tested the potential correlation between circulating oxysterols and fatty acids., Methods: 60 obese patients and 75 patients with metabolic syndrome were enrolled in the study along with 210 age- and sex-matched healthy subjects, used as control group. Plasma oxysterols were analyzed by isotope dilution GC/MS, and plasma fatty acids profiling was assessed by gas chromatography coupled with flame ionization detection., Results: We found considerable differences in oxysterols profiling in the two disease groups that were gender-related. Compared to controls, males showed significant differences only in 4α- and 4β-hydroxycholesterol levels in obese and metabolic syndrome patients. In contrast, females showed consistent differences in 7-oxocholesterol, 4α-hydroxycholesterol, 25-hydroxycholesterol and triol. Concerning fatty acids, we found minor differences in the levels of these variables in males of the three groups. Significant changes were observed in plasma fatty acid profile of female patients with obesity or metabolic syndrome. We found significant correlations between various oxysterols and fatty acids. In particular, 4β-hydroxycholesterol, which is reduced in obesity and metabolic syndrome, correlated with a number of saturated and mono-unsaturated fatty acids that are end-products of de novo lipogenesis., Conclusions: Our data provide the first evidence that obesity and metabolic syndrome are associated with major, gender-specific, changes in circulating oxysterols and fatty acids. These findings suggest a metabolic link between oxysterols and fatty acids, and that oxysterols may contribute to the epidemic diseases associated with obesity and metabolic syndrome in female., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Bisphenol A (BPA) is a suspected endocrine disruptor highly prevalent in our environment since it is used as monomer of polycarbonate plastics and epoxy resins. Recent epidemiological and animal studies have suggested that BPA exposure may influence the development of obesity and related pathologies such as type 2 diabetes, and cardiovascular diseases. However, experimental studies have often focused on short-term exposures. In this study, we investigated the effect of several months of BPA exposure on hepatic and plasma metabolic markers in adult mice. Male CD1 mice were exposed during 8 months to five different BPA doses below or equivalent to the current no observed adverse effect level (NOAEL: 5000 μg/kg/day) through drinking water. Plasma lipid profiles and liver transcriptomic analysis were performed in control and BPA-treated animals. We report a specific impact of BPA exposure on glycaemia, glucose tolerance and cholesterolemia. Consistent with the hypercholesterolemia in BPA-treated animals, RT-qPCR performed on hepatic mRNA from same animals demonstrated an overexpression of key genes involved in cholesterol biosynthesis, namely, Mvd, Lss Hmgcr, and Sqle. BPA also induced the expression of the sterol regulatory element-binding proteins 2, a master regulator of hepatic cholesterol biosynthesis. As shown by the plasma lathosterol to cholesterol ratio, a surrogate marker for cholesterol biosynthesis, whole body cholesterol de novo synthesis was also increased in BPA-exposed animals. These original results are consistent with many epidemiological studies reporting on a link between BPA exposure and the onset of cardiovascular diseases., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background & Aims: Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified., Methods: We used wild type mice and mice lacking Liver X Receptors to perform a nutrigenomic study that aimed at examining the role of these transcription factors., Results: We showed that, in the absence of Liver X Receptors, essential fatty acids deficiency does not promote steatosis. Consistent with this, Liver X Receptors are required for the elevated expression of genes involved in lipogenesis in response to essential fatty acids deficiency., Conclusions: This work identifies, for the first time, the central role of Liver X Receptors in steatosis induced by essential fatty acids deficiency., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)