Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation

Background and Aims Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult population. A significant subset of patients are lean, but their underlying pathophysiology is not well understood. Approach and Results We investigated the role of bile acids (BAs) and the gut microbiome in...

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Veröffentlicht in:	Hepatology (Baltimore, Md.) Md.), 2020-04, Vol.71 (4), p.1213-1227
Hauptverfasser:	Chen, Fei, Esmaili, Saeed, Rogers, Geraint B., Bugianesi, Elisabetta, Petta, Salvatore, Marchesini, Giulio, Bayoumi, Ali, Metwally, Mayada, Azardaryany, Mahmoud Karimi, Coulter, Sally, Choo, Jocelyn M., Younes, Ramy, Rosso, Chiara, Liddle, Christopher, Adams, Leon A., Craxì, Antonio, George, Jacob, Eslam, Mohammed
Format:	Artikel
Sprache:	eng
Schlagworte:	Adult Animal models Animals Bile acids Bile Acids and Salts - metabolism Biopsy Cyclic N-Oxides - therapeutic use Digestive system Disease Models, Animal Fatty liver Female Fibroblast growth factors Fibroblast Growth Factors - blood Fibrosis Gastrointestinal Microbiome Gastrointestinal tract Hepatology Humans Intestinal microflora Intestine Liver diseases Male Metabolism Mice Mice, Inbred C57BL Microbiomes Microbiota Middle Aged Non-alcoholic Fatty Liver Disease - drug therapy Non-alcoholic Fatty Liver Disease - metabolism Non-alcoholic Fatty Liver Disease - microbiology Pathogenesis Phospholipase Phospholipases A2, Calcium-Independent Receptors, Cytoplasmic and Nuclear - metabolism Thinness - metabolism Tropanes - therapeutic use
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Zusammenfassung:	Background and Aims Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult population. A significant subset of patients are lean, but their underlying pathophysiology is not well understood. Approach and Results We investigated the role of bile acids (BAs) and the gut microbiome in the pathogenesis of lean NAFLD. BA and fibroblast growth factor (FGF) 19 levels (a surrogate for intestinal farnesoid X receptor [FXR] activity), patatin‐like phospholipase domain containing 3 (PNPLA3), and transmembrane 6 superfamily member 2 (TM6SF2) variants, and gut microbiota profiles in lean and nonlean NAFLD were investigated in a cohort of Caucasian patients with biopsy‐proven NAFLD (n = 538), lean healthy controls (n = 30), and experimental murine models. Patients with lean NAFLD had a more favorable metabolic and histological profile compared with those with nonlean NAFLD (P
ISSN:	0270-9139 1527-3350
DOI:	10.1002/hep.30908