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The metabolic syndrome encompasses metabolic and cardiovascular risk factors which predict diabetes and cardiovascular disease (CVD) better than any of its individual components. Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum which includes variable degrees of simple steatosis (nonalcoholic fatty liver, NAFL), nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the hepatic manifestation of the metabolic syndrome, with insulin resistance as the main pathogenetic mechanism. Recent data indicate that hyperinsulinemia is probably the consequence rather than cause of NAFLD and NAFLD can be considered an independent predictor of cardiovascular disease. Serum free fatty acids derived from lipolysis of visceral adipose tissue are the main source of hepatic triglycerides in NAFLD, although hepatic de novo lipogenesis and dietary fat supply contribute to the pathogenesis of NAFLD. Approximately 10-25% NAFLD patients develop NASH, the evolutive form of hepatic steatosis. Presumably in a genetically predisposed environment, this increased lipid overload overwhelms the oxidative capacity and reactive oxygen species are generated, leading to lipid peroxidation, cytokine induction, chemoattraction of inflammatory cells, hepatic stellate cell activation and finally fibrogenesis with extracellular matrix deposition. No currently available therapies for NAFLD and NASH exist. Recently nuclear receptors have emerged as key regulators of lipid and carbohydrate metabolism for which specific pharmacological ligands are available, making them attractive therapeutic targets for NAFLD and NASH.Abbreviations ALT, alanine aminotransferase; BMI, body mass index; CVD, cardiovascular disease; FFA, free fatty acids; HDL, high density lipoprotein; 1H-MRS, proton magnetic resonance spectroscopy; IDF, International Diabetes Federation; LDL, low density lipoprotein; NAFLD, nonalcoholic fatty liver disease; SNP, single nucleotide polymorphism; VLDL, very low density lipoprotein IntroductionThe metabolic syndrome is a cluster of metabolic and cardiovascular risk factors which predicts diabetes and cardiovascular disease (CVD) better than any of its individual components [1]. The latest definition of the metabolic syndrome by International Diabetes Federation (IDF) includes abdominal obesity defined by increased waist circumference (≥94 cm in men and ≥80 cm in women) and two or more of the following features: elevated blood pressure, fasting glucose or triglyceride concentrations, or low HDL cholesterol [1]. The term nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum which includes variable degrees of simple steatosis (nonalcoholic fatty liver, NAFL), nonalcoholic steatohepatitis (NASH) and cirrhosis [2] and [3]. NAFLD can be considered the hepatic manifestation of the metabolic syndrome. Simple steatosis is benign, whereas NASH is defined by the presence of hepatocyte injury, inflammation and/or fibrosis which can lead to cirrhosis, liver failure and hepatocellular carcinoma. In contrast to t...

Surgery or radiation therapy of metastatic cancer often damages lymph nodes, leading to secondary lymphedema. Here we show, using a newly established mouse model, that collecting lymphatic vessels can be regenerated and fused to lymph node transplants after lymph node removal. Treatment of lymph node-excised mice with adenovirally delivered vascular endothelial growth factor-C (VEGF-C) or VEGF-D induced robust growth of the lymphatic capillaries, which gradually underwent intrinsic remodeling, differentiation and maturation into functional collecting lymphatic vessels, including the formation of uniform endothelial cell-cell junctions and intraluminal valves. The vessels also reacquired pericyte contacts, which downregulated lymphatic capillary markers during vessel maturation. Growth factor therapy improved the outcome of lymph node transplantation, including functional reconstitution of the immunological barrier against tumor metastasis. These results show that growth factor-induced maturation of lymphatic vessels is possible in adult mice and provide a basis for future therapy of lymphedema.

Liver fat content is significantly increased in subjects with the metabolic syndrome as compared with those without the syndrome, independently of age, gender, and body mass index. Of other markers, serum C-peptide is the strongest correlate of liver fat.