Liver plays an essential role in regulating lipid metabolism, and chronically disturbed hepatic metabolism may cause obesity and metabolic syndrome, which may lead to non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates long noncoding RNAs (lncRNAs) play an important role in energy metabolism. Here, we investigated the role of lncRNA H19 in hepatic lipid metabolism and its potential association with NAFLD. We found that H19 was up-regulated in oleic acid-induced steatosis and during the development of high-fat diet (HFD)-induced NAFLD. Exogenous overexpression of H19 in hepatocytes induced lipid accumulation and up-regulated the expression of numerous genes involved in lipid synthesis, storage and breakdown, while silencing endogenous H19 led to a decreased lipid accumulation in hepatocytes. Mechanistically, H19 was shown to promote hepatic steatosis by up-regulating lipogenic transcription factor MLXIPL. Silencing Mlxipl diminished H19-induced lipid accumulation in hepatocytes. Furthermore, H19-induced lipid accumulation was effectively inhibited by PI3K/mTOR inhibitor PF-04691502. Accordingly, H19 overexpression in hepatocytes up-regulated most components of the mTORC1 signalling axis, which were inhibited by silencing endogenous H19. In vivo hepatocyte implantation studies further confirm that H19 promoted hepatic steatosis by up-regulating both mTORC1 signalling axis and MLXIPL transcriptional network. Collectively, these
Objective: To derive age-and sex-specific reference values for waist circumference (WC) and waist-to-height ratio (WHtR) for Han Chinese children and adolescents and to establish the prevalence of excess central adiposity in our study population. Design: Cross-sectional study of schoolchildren attending randomly selected primary and secondary schools in south-west China in October 2003 and April 2004. Anthropometry was measured using standard procedures. The LMS method was used to construct smoothed WC and WHtR percentile curves. Overweight and obesity were defined by the International Obesity Task Force (IOTF) criteria and the Working Group on Obesity in Children. Excess central adiposity fat was defined by previously published WC cut-points and a WHtR $ 0?5. Setting: Primary and secondary schools in Chongqing, south-west China. Subjects: A total of 7326 (49?2 % boys) Han Chinese students at 5-17 years old. Results: On the basis of the IOTF criteria, 26?4 % of boys were overweight or obese compared with 16?4 % of girls (P , 0?001). WC cut-points identified 31 % of boys and 28 % of girls as having excess central adiposity, whereas using the WHtR criterion, 14?8 % of boys and 5?6 % of girls were identified. Young boys (5-12 years) had a significantly (P , 0?001) higher WHtR than girls. Conclusions: We have constructed WC and WHtR percentile curves for Han Chinese children and adolescents living in Chongqing. Our measurements were based on a student population with a relatively high rate of overweight and obesity. These data will provide a point of reference for future studies measuring the prevalence of overweight and obesity in China.
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