Alanine and aspartate aminotransferase and glutamine-cycling pathway: their roles in pathogenesis of metabolic syndrome.

Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome (MS), the pathogenesis and pathophysiology of this complex disease remains a major challenge. Interestingly, Cheng et al recently investigated possible pathways underlying MS by high-throughput metabolite profiling in two large and well characterized community-based cohorts. The authors explored by liquid chromatography and mass spectrometry the plasma concentrations of 45 distinct metabolites and examined their relation to cardiometabolic risk, and observed that metabolic risk factors such as obesity, insulin resistance (IR), high blood pressure, and dyslipidemia were associated with several metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites.

The genetic epidemiology of nonalcoholic fatty liver disease: toward a personalized medicine.

The understanding of the genetic bases of complex diseases such as nonalcoholic fatty liver disease opens new opportunities and challenges. This article explores new tools designed toward moving genomic data into clinical medicine, providing putative answers to more practical questions.

DNA methylation and hepatic insulin resistance and steatosis.

Purpose Of Review: In this review, we show novel evidence about the role of the liver in the development of insulin resistance and suggest that abnormal hepatic triglyceride accumulation is not an innocent bystander comorbidity but adversely affects the peripheral insulin sensitivity.

Recent Findings: The core of this review is built up around the concept that liver DNA methylation of the peroxisome proliferative activated receptor gamma coactivator one alpha gene promoter modulates the status of peripheral insulin resistance and is strongly associated with plasma fasting insulin levels. We discuss about other mechanisms associated with peroxisome proliferative activated receptor gamma coactivator one alpha regulation, such as an acetylation and deacetylation switch and how these events impact on the liver metabolic function.

Genetic determinants of acquired cholestasis: a systems biology approach.

Cholestatic liver diseases encompass a complex spectrum of intrahepatic and cholangiocellular cholestasis, whose etiologies include genetic and environmental components. This review focuses on the role of the genetic component of three adult cholestatic diseases, namely, primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), and intrahepatic cholestasis of pregnancy (ICP). In particular, we integrate genomic, molecular, and physiological data to understand the putative interplay between the underlying genetic mechanisms involved in the susceptibility of these diseases.

Liver transcriptional profile of atherosclerosis-related genes in human nonalcoholic fatty liver disease.

Objectives And Design: Epidemiological studies have suggested a role of nonalcoholic fatty liver disease (NAFLD) in the development of cardiovascular disease. We evaluated liver mRNA expression of 84 genes encoding proteins involved in the atherosclerosis pathway in patients with NAFLD proven through biopsy in a case-control design, and examined the putative role of the histological disease severity in the molecular events associated with the atherogenic profile.

Results: Nonalcoholic steatohepatitis (NASH), when compared with simple steatosis (SS), significantly increases the expression of TGFB1 (6.

Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease.

Unlabelled: Our objective was to estimate the strength of the effect of the I148M (rs738409 C/G) patatin-like phospholipase domain containing 3 (PNPLA3) variant on nonalcoholic fatty liver (NAFLD) and disease severity across different populations. We performed a systematic review by a meta-analysis; literature searches identified 16 studies. Our results showed that rs738409 exerted a strong influence not only on liver fat accumulation (GG homozygous showed 73% higher lipid fat content when compared with CC ones, data from 2,937 subjects; P < 1 × 10(-9) ), but also on the susceptibility of a more aggressive disease (GG homozygous had 3.

Odor perception between heterosexual partners: its association with depression, anxiety, and genetic variation in odorant receptor OR7D4.

We performed a study on a sample of 856 individuals to answer whether the pleasantness/unpleasantness of the odor perception of their partners (rating of partner odor) is associated with depression and anxiety. To evaluate the influence of common genetic variation of the odorant receptor OR7D4 on the rating of partner odor, the variant rs8109935 was genotyped in the whole sample. The rating of partner odor was significantly associated with scores of anxiety and depression.

Metabolic syndrome: from the genetics to the pathophysiology.

The metabolic syndrome (MS) constitutes a combination of underlying risk factors for an adverse outcome, cardiovascular disease. Thus, the clinical behavior of the MS can be regarded as a whole. Nevertheless, from a pathogenic point of view, understanding of the underlying mechanisms of each MS intermediate phenotype is far beyond their understanding as an integrative process.

Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor γ coactivator 1α promoter.

Unlabelled: Insulin resistance (IR) and mitochondrial dysfunction play a central role in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). We hypothesized that genetic factors and epigenetic modifications occurring in the liver contribute to the IR phenotype. We specifically examined whether fatty liver and IR are modified by hepatic DNA methylation of the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) and mitochondrial transcription factor A (TFAM) promoters, and also evaluated whether liver mitochondrial DNA (mtDNA) content is associated with NAFLD and IR.

High fat diet-induced liver steatosis promotes an increase in liver mitochondrial biogenesis in response to hypoxia.

Mitochondrial DNA (mtDNA) copy number plays a key role in the pathophysiology of metabolic syndrome-related phenotypes, but its role in non-alcoholic fatty liver disease (NAFLD) is not well understood. We evaluated the molecular mechanisms that may be involved in the regulation of liver mtDNA content in a high-fat-induced rat model of NAFLD. In particular, we tested the hypothesis that liver mtDNA copy number is associated with liver expression of HIF-1α.