Fatty liver, cardiometabolic disease and mortality Purpose of review We discuss the findings of the most recent metanalyses on the association between nonalcoholic fatty liver disease (NAFLD), cardiometabolic disease and mortality. Recent findings Recent metanalyses have shown that NAFLD is associated with incident type 2 diabetes mellitus (T2DM) and incident cardiovascular disease (CVD). Nonalcoholic steatohepatitis, which can be diagnosed by liver biopsy only in tertiary care centers, is often associated with liver fibrosis, which has been shown by metanalyses to increase both cardiovascular and liver-related mortality. Hyperlipidemia, lipotoxicity and impaired insulin secretion are among the possible mechanisms underlying the association of NAFLD with T2DM and CVD. Metanalyses of the association between NAFLD and mortality in the general population, where risk stratification cannot be performed on the basis of liver biopsy, have given contradictory results. Summary To establish conclusively whether NAFLD adds to known prognostic factors of death in the general population will require a shared operational definition of NAFLD, purposefully designed cohort studies, and the use of clinically relevant measures of effect size. Correspondence to Giorgio Bedogni, Clinical Epidemiology Unit, Liver Research Center, Building Q, AREA Science Park, Strada Statale 14 km 163.5, 34012 Basovizza, Trieste, Italy. E-mail: giorgiobedogni@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Metabolomic and gene expression analysis to study the effects of dietary saturated and polyunsaturated fats Purpose of review Give an update on recent dietary intervention studies that have used peripheral blood mononuclear cell gene expression analysis and/or metabolic profiling to understand how intake of polyunsaturated and saturated fat affects and biological pathways linked to cardiovascular disease. Recent findings Several studies showed that intake of fish oil and vegetable oil, high in omega-3 fatty acids, reduced expression level of genes involved in inflammation. One intervention study showed that gene transcripts encoding genes involved inflammation and lipid metabolism increased after intake of polyunsaturated fat (mainly omega-6 fatty acids) compared to saturated fat. Additionally, using targeted metabolomics, the concentrations of atherogenic lipoprotein particles and several metabolites including palmitoylcarnitine, myristoylcarnitine, and kynurenine were reduced after intake of polyunsaturated fat compared to saturated fat, whereas acetate and acetoacetate were increased. The use of targeted metabolomics showed that overfeeding with polyunsaturated fat reduced the serum concentration of ceramides, dihydroceramides, glucosylceramides, and lactosylceramides, whereas overfeeding with saturated fat increased serum concentration of these metabolites. Summary The use of gene expression profiling and metabolomics are promising tools to identify possible new biomarkers linking fat quality to cardiovascular disease risk. Correspondence to Stine M. Ulven, Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, P.O. Box 1046, 0317 Blindern, Oslo, Norway. Tel: +47 22 84 02 08; e-mail: smulven@medisin.uio.no Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Dietary fructose and dyslipidemia: new mechanisms involving apolipoprotein CIII Purpose of review Chronic consumption of fructose and fructose-containing sugars leads to dyslipidemia. Apolipoprotein (apo) CIII is strongly associated with elevated levels of triglycerides and cardiovascular disease risk. We reviewed the effects of fructose consumption on apoCIII levels and the role of apoCIII in fructose-induced dyslipidemia. Recent findings Consumption of fructose increases circulating apoCIII levels compared with glucose. The more marked effects of fructose compared with glucose on apoCIII concentrations may involve the failure of fructose consumption to stimulate insulin secretion. The increase in apoCIII levels after fructose consumption correlates with increased postprandial serum triglyceride. Further, RNA interference of apoCIII prevents fructose-induced dyslipidemia in nonhuman primates. Increases in postprandial apoCIII after fructose, but not glucose consumption, are positively associated with elevated triglycerides in large triglyceride-rich lipoproteins and increased small dense LDL levels. Summary ApoCIII might be causal in the lipid dysregulation observed after consumption of fructose and fructose-containing sugars. Decreased consumption of fructose and fructose-containing sugars could be an effective strategy for reducing circulating apoCIII and subsequently lowering triglyceride levels. Correspondence to Kimber L. Stanhope, Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA. Tel: +1 530 752 3720; fax: +1 530 752 2474; e-mail: klstanhope@ucdavis.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.