|
| References | Model | Agent, mechanism, and duration | Findings |
|
| McMahan et al. [98] | Obese db/db mice with NAFLD | INT-767, dual FXR/TGR5 agonist, 6 weeks | (1) Improved the histological features of NAFLD
(2) Increased the proportion of intrahepatic monocytes with the anti-inflammatory phenotype |
| Roth et al. [99] | ob/ob mice with NAFLD | INT-767, dual FXR/TGR5 agonist, 6 weeks | (1) Improved the histological features of NAFLD
(2) Reduced liver fibrosis, inflammation, and hepatocyte lipid droplet area |
| Jadhav et al. [100] | TGR5, FXR, Apoe, and SHP knockout mice with diet-induced NAFLD | INT-767, dual FXR/TGR5 agonist, 12 weeks | (1) Reversed atherosclerosis and NAFLD
(2) Reduced high-fat diet-induced obesity dependent on activation of both TGR5 and FXR |
| Hu et al. [101] | High-fat diet-induced rat NAFLD | INT-767, dual FXR/TGR5 agonist, 4 weeks | (1) Reduced lipid accumulation and hepatic infiltration of immune cells
(2) Restored lipid and glucose metabolism |
| Comeglio et al. [102] | High-fat diet-induced rabbit metabolic syndrome | INT-767, dual FXR/TGR5 agonist, 12 weeks | (1) Alleviated NAFLD and fat alterations
(2) Restored insulin sensitivity and induced preadipocytes toward a metabolically healthy phenotype |
| Ma et al. [103] | High-fat diet-induced mouse NAFLD | GW4064, FXR agonist, 6 weeks | (1) Ameliorated NAFLD and liver inflammation
(2) Reversed diet-induced hyperinsulinemia and hyperglycemia |
| de Oliveira et al. [104] | Ovariectomized and high-fat diet-induced mouse NAFLD | OCA (FXR) and INT-777 (TGR5), 4 weeks | (1) Corrected NAFLD and metabolic changes
(2) Elevated energy expenditure and expression of key metabolic genes |
| Haczeyni et al. [105] | Dietary and metabolic obesity mouse NAFLD | OCA, 24 weeks | Improved glucose tolerance and NAFLD in dietary but not metabolic obesity mouse |
| Liles et al. [106] | High-fat, cholesterol, and sugar diet-induced mouse NAFLD | GS-9674, FXR agonist, 90 days | (1) Improved the histological features of NAFLD
(2) Decreased serum transaminases and liver fibrosis |
| Zheng et al. [107] | High-fat diet-induced mouse NAFLD | Altenusin, FXR agonist, 3 weeks | (1) Reversed NAFLD, alleviated dyslipidemia and insulin resistance, and reduced body weight and fat mass
(2) No effect on FXR knockout mice |
| Zhang et al. [108] | MCD diet-induced mouse NAFLD | WAY-362450, FXR agonist, 4 weeks | (1) Reduced inflammatory cell infiltration and fibrosis
(2) Protection was lost in FXR knockout mice |
| Carino et al. [109] | High-fat/high-fructose diet-induced NAFLD | BAR502, dual FXR/TGR5 agonist, 8 weeks | (1) Alleviated NAFLD, increased insulin sensitivity, and elevated circulating levels of HDL
(2) Improved browning of white fat tissue |
| Carino et al. [110] | High-fat/high-fructose diet-induced NAFLD | BAR501, TGR5 agonist, 9 weeks | (1) Reversed insulin resistance and NAFLD
(2) Promoted energy expenditure and the browning of white fat tissue. Lost effect in TGR5 knockout mice |
| Jin et al. [111] | High-fat diet-induced mouse NAFLD | Avermectin, FXR agonist, 14 days | (1) Ameliorated NAFLD, reduced glucose levels, and improved insulin sensitivity
(2) Protection was FXR dependent |
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