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The single nucleotide polymorphism I148M of the lipase patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an unfavorable prognosis in alcoholic and non-alcoholic steatohepatitis (ASH, NASH), with progression to liver cirrhosis and development of hepatocellular carcinoma. In this study, we investigated the mechanistic interaction of PNPLA3 with lipid droplet (LD)-associated proteins of the perilipin family, which serve as gatekeepers for LD degradation. In a collective of 106 NASH, ASH and control liver samples, immunohistochemical analyses revealed increased ballooning, inflammation and fibrosis, as well as an accumulation of PNPLA3–perilipin 5 complexes on larger LDs in patients homo- and heterozygous for PNPLA3(I148M). Co-immunoprecipitation demonstrated an interaction of PNPLA3 with perilipin 5 and the key enzyme of lipolysis, adipose triglyceride lipase (ATGL). Localization studies in cell cultures and human liver showed colocalization of perilipin 5, ATGL and PNPLA3. Moreover, the lipolytic activity of ATGL was negatively regulated by PNPLA3 and perilipin 5, whereas perilipin 1 displaced PNPLA3 from the ATGL complex. Furthermore, ballooned hepatocytes, the hallmark of steatohepatitis, were positive for PNPLA3 and perilipins 2 and 5, but showed decreased perilipin 1 expression with respect to neighboured hepatocytes. In summary, PNPLA3- and ATGL-driven lipolysis is significantly regulated by perilipin 1 and 5 in steatohepatitis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk factors for unintentional injury among children in the rural areas of Liling, Hunan Province, China, as a basis for developing prevention and intervention measures for unintentional injury in rural children., Methods: A total of 3 257 students, aged between 5 and 16 years from 4 middle schools and 2 primary schools in eastern and western rural areas of Liling were recruited in October 2013 by stratified sampling and cluster sampling. The general personal information and data on family backgrounds, living environment, and incidence of unintentional injury were collected from all subjects through a self-designed questionnaire. The risk factors for childhood unintentional injury were assessed by an unconditional multiple logistic regression analysis., Results: Out of the 3 257 subjects, 356 (10.93%) were injured during the 12-month period prior to the study. The univariate analysis showed that unintentional injury in these subjects was related to sex, left-behind status, times of internet surfing in internet bars per week, parent companion or not, age of guardian, degree of harmony of parents' marital relationship, employment status of one or both parents as a migrant worker, storage of fireworks and firecrackers at home or not, violence in residential areas, and participation or not in violence in residential areas. The unconditional multiple logistic regression analysis showed that the major risk factors for unintentional injury in these subjects were male gender (OR=0.751, P=0.013), left-behind status (OR=1.779, P<0.001), storage of fireworks and firecrackers at home (OR=1.337, P=0.028) and violence around residential areas (OR=1.517, P<0.001)., Conclusions: Risk for unintentional injury is multifactorial among children in the rural areas of Liling, Hunan. To reduce the incidence of unintentional injury in children in Liling, particular attention should be paid to boys, left-behind children, children who have home storage of fireworks and firecrackers and children who are living in areas with frequent violence.