Patatin-like phospholipase domain-containing 3(PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism,and has been reported to be significantly associated with liver fat content.Variouss...Patatin-like phospholipase domain-containing 3(PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism,and has been reported to be significantly associated with liver fat content.Variousstudies have established a strong link between the 148 isoleucine to methionine protein variant(I148M) of PNPLA3 and liver diseases,including nonalcoholic fatty liver disease(NAFLD).However,detailed demographic and ethnic characteristics of the I148 M variant and its role in the development of nonalcoholic fatty liver fibrosis have not been fully elucidated.The present review summarizes the current knowledge on the association between the PNPLA3 I148 M variant and NAFLD,and especially its role in the development of nonalcoholic fatty liver fibrosis.First,we analyze the impact of demographic and ethnic characteristics of the PNPLA3 I148 M variant and the presence of metabolic syndrome on the association between PNPLA3 I148 M and NAFLD.Then,we explore the role of the PNPLA3 I148 M in the development of nonalcoholic fatty liver fibrosis,and hypothesize the underlying mechanisms by speculating a pro-fibrogenic network.Finally,we briefly highlight future research that may elucidate the specific mechanisms of the PNPLA3 I148 M variant in fibrogenesis,which,in turn,provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.展开更多
基金Supported by National Natural Science Foundation of China No.81170337/H0304
文摘Patatin-like phospholipase domain-containing 3(PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism,and has been reported to be significantly associated with liver fat content.Variousstudies have established a strong link between the 148 isoleucine to methionine protein variant(I148M) of PNPLA3 and liver diseases,including nonalcoholic fatty liver disease(NAFLD).However,detailed demographic and ethnic characteristics of the I148 M variant and its role in the development of nonalcoholic fatty liver fibrosis have not been fully elucidated.The present review summarizes the current knowledge on the association between the PNPLA3 I148 M variant and NAFLD,and especially its role in the development of nonalcoholic fatty liver fibrosis.First,we analyze the impact of demographic and ethnic characteristics of the PNPLA3 I148 M variant and the presence of metabolic syndrome on the association between PNPLA3 I148 M and NAFLD.Then,we explore the role of the PNPLA3 I148 M in the development of nonalcoholic fatty liver fibrosis,and hypothesize the underlying mechanisms by speculating a pro-fibrogenic network.Finally,we briefly highlight future research that may elucidate the specific mechanisms of the PNPLA3 I148 M variant in fibrogenesis,which,in turn,provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.
