Background & Aims: Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration and in hepatocellular carcinoma (HCC). However, the metabolic control of these processes is not fully understood. In order to capture the metabolic signature of proliferating hepatocytes, we applied state-of-the-art systems biology approaches to models of liver regeneration, pharmacologically-and genetically-activated cell proliferation, and HCC.

In studies of mice, we found intestinal SCD1 to be required for synthesis of oleate in the enterocytes and maintenance of fatty acid homeostasis. Dietary supplementation with oleic acid reduces intestinal inflammation and tumor development in mice.

Analysis of oxylipins by liquid chromatography mass spectrometry (LC-MS) is challenging because of the small mass range occupied by this diverse lipid class, the presence of numerous structural isomers, and their low abundance in biological samples. Although highly sensitive LC-MS/MS methods are commonly used, further separation is achievable by using drift tube ion mobility coupled with high-resolution mass spectrometry (DTIM-MS). Herein, we present a combined analytical and computational method for the identification of oxylipins and fatty acids. We use a reversed-phase LC-DTIM-MS workflow able to profile and quantify (based on chromatographic peak area) the oxylipin and fatty acid content of biological samples while simultaneously acquiring full scan and product ion spectra. The information regarding accurate mass, collision-cross section values in nitrogen (DT CCSN2) and retention times of the species found are compared to an internal library of lipid standards as well as the LIPID MAPS Structure Database by using specifically developed processing tools. Features detected within the DT CCSN2 and m/z ranges of the analyzed standards are flagged as oxylipin-like species, which can be further characterized using drift time alignment of product and precursor ions distinctive of DTIM-MS. This not only helps identification by reducing the number of annotations from LIPID MAPS, but also guides discovery studies of potentially novel species. Testing the methodology on Salmonella enterica serovar Typhimurium infected murine bone-marrow derived macrophages and thrombin activated human platelets yields results in agreement with literature. This workflow has also annotated features as potentially novel oxylipins, confirming its ability in providing further insights into lipid analysis of biological samples.

Non-alcoholic fatty liver disease (NAFLD) is defined as excessive triglyceride accumulation into the hepatocytes in the absence of excessive alcohol consumption and defined by the presence of steatosis in >5% of hepatocytes according to histological analysis or by >5.6% hepatic fat assessed by magnetic resonance imaging (MRI) or spectroscopy (MRS). 1 It is estimated that the prevalence of non-alcoholic fatty liver disease (NAFLD) in the general

Current evidence suggests a beneficial effect of the Mediterranean diet (MD) on human health. This has led to a rise in studies investigating the role of the MD in cardiovascular disease (CVD) prevention outside the region of its origin. We aimed to outline the evolving understanding of the MD and to provide an overview of adherence to MD in non-Mediterranean countries and the modulatory effects of MD on CVD biomarkers. Evidence suggest that MD may exert a protective effect on CVD via ameliorating blood lipid profile and blood pressure. A protective effect of MD was found with regard to left ventricular mass but data on carotid intima media thickness and pulse wave velocity are lacking. The paucity of data does not give a clear picture of the health effects of the MD in non-Mediterranean countries, thus larger and well-designed studies on MD outside the Mediterranean countries are warranted.

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The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated “omics” approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the “lysophosphatidylcholines to phosphatidylcholines” and “cholesteryl ester to free cholesterol” ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated “omics” approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis.

No abstract