The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understoo...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2016/2862173 |
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| author | Jinsheng Yu Sharon Marsh Junbo Hu Wenke Feng Chaodong Wu |
| author_facet | Jinsheng Yu Sharon Marsh Junbo Hu Wenke Feng Chaodong Wu |
| author_sort | Jinsheng Yu |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression. |
| format | Article |
| id | doaj-art-48ab680df2e2442591d6523428ffb626 |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
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| series | Gastroenterology Research and Practice |
| spelling | doaj-art-48ab680df2e2442591d6523428ffb6262025-02-03T01:25:05ZengWileyGastroenterology Research and Practice1687-61211687-630X2016-01-01201610.1155/2016/28621732862173The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic BackgroundJinsheng Yu0Sharon Marsh1Junbo Hu2Wenke Feng3Chaodong Wu4Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USAFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H7, CanadaDepartment of General Surgery, Tongji Hospital, Huazhong Science & Technology University, Wuhan, Hubei 430030, ChinaDepartment of Medicine, University of Louisville, Louisville, KY 40208, USADepartment of Nutrition and Food Science, Texas A&M University, Houston, TX 77843, USANonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression.http://dx.doi.org/10.1155/2016/2862173 |
| spellingShingle | Jinsheng Yu Sharon Marsh Junbo Hu Wenke Feng Chaodong Wu The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background Gastroenterology Research and Practice |
| title | The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background |
| title_full | The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background |
| title_fullStr | The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background |
| title_full_unstemmed | The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background |
| title_short | The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background |
| title_sort | pathogenesis of nonalcoholic fatty liver disease interplay between diet gut microbiota and genetic background |
| url | http://dx.doi.org/10.1155/2016/2862173 |
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