Ethanol and its major metabolite acetate both induced histone H3 acetylation in primary culture of rat hepatocytes. The acetylation by ethanol was dependent on the reactive oxygen species and mitogen-activated protein kinase pathway, whereas that by acetate was independent of both pathways. Ethanol increased CYP2E1 protein expression but acetate had negligible effect. The level of phospho-H2AX,...

Genome-wide association studies (GWAS) have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeo...

Members of the Patatin-like Phospholipase Domain containing Protein A (PNPLA) family play key roles in triglyceride hydrolysis, energy metabolism, and lipid droplet (LD) homoeostasis. Here we report the identification of two distinct LD targeting motifs (LTM) for PNPLA family members. Transient transfection of truncated versions of human adipose triglyceride lipase (ATGL, also known as PNPLA2),...

We conducted a meta-analysis to assess the association between patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) and its subtypes simple steatosis(SS) and nonalcoholic steatohepatitis (NASH). The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models...

OBJECTIVE Genetic variation in six genes has been associated with elevated liver fat and nonalcoholic fatty liver disease in adults. The influence of these genes on liver fat and whether a genetic risk score (GRS) would improve upon the ability of common clinical risk factors to predict elevated liver fat content (ELF) in Hispanic children was determined. DESIGN AND METHODS 223 obese Hispanic...

The genetic factors affecting the natural history of nonalcoholic fatty liver disease (NAFLD), including the development of nonalcoholic steatohepatitis (NASH) and NASH-derived hepatocellular carcinoma (NASH-HCC), are still unknown. In the current study, we sought to identify genetic factors related to the development of NAFLD, NASH, and NASH-HCC, and to establish risk-estimation models for the...

Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A's functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central ro...

沖縄県は脂肪肝有病率が本邦において最も高いため，疾患感受性遺伝子であるpatatinlike phospholipase domain containing 3（PNPLA3）の一塩基多型（rs2896019）との関連を調べた。解析対象者として，健診受診者178名から36名（男性18名，女性18名）の肝腎コントラスト陽性者，年齢・性別を対応させた38名（男性19名，女性19名）の陰性者の計74名を抽出し，結果を横断研究に用いた。女性に比べて男性の肝腎コントラスト陽性率が高かった（p＝0.0020）。PNPLA3 SNP解析では，TTの比率は16.2％，GT/TGは58.1％，GGは25.7％であった。女性では，肝腎コントラスト陽性者のBMIおよび体脂肪率は陰性者に比べて高値を示した（p＝0.0003，p＜0.0001）。女性の体脂肪率（％）では，TT（29.8±7.1）に比べてGG（...