Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats

• Published in: British journal of nutrition 2016-07, Vol.116 (2), p.191-203
• Main Authors: Jegatheesan, Prasanthi, Beutheu, Stéphanie, Freese, Kim, Waligora-Dupriet, Anne-Judith, Nubret, Esther, Butel, Marie-Jo, Bergheim, Ina, De Bandt, Jean-Pascal
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Bacteroides; Bacteroides - drug effects; Bacteroides - growth & development; Citrulline - pharmacology; Citrulline - therapeutic use; Claudin-1 - metabolism; Colon - drug effects; Colon - metabolism; Colon - microbiology; Diet; Diet, Western - adverse effects; Drinking water; Endoplasmic Reticulum Stress - drug effects; Inflammation - metabolism; Inflammation - prevention & control; Injuries; Insulin - blood; Insulin Resistance; Interleukin-6 - metabolism; Lipid Droplets; Liver; Liver - drug effects; Liver - metabolism; Male; Molecular Nutrition; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; Prevotella; Prevotella - drug effects; Prevotella - growth & development; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Rodents; Studies; Toll-Like Receptor 4 - metabolism; Translocation; Triglycerides - blood; Triglycerides - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114516001793

A Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague–Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks. The high-fat, high-fructose diet (Western diet) was fed either alone (group WD) or with Cit (1 g/kg per d) (group WDC) or an isonitrogenous amount of non-essential amino acids (group WDA). We evaluated nutritional and metabolic status, liver function, intestinal barrier function, gut microbiota and splanchnic inflammatory status. Cit led to a lower level of hepatic TAG restricted to microvesicular lipid droplets and to a lower mRNA expression of CCAAT-enhancer-binding protein homologous protein, a marker of endoplasmic reticulum stress, of pro-inflammatory cytokines Il6 (P