Four-week-old male and female C57BL/6N mice were obtained from the Central Lab Animal Inc. (Seoul, South Korea) and housed in 42 x 27 x 15 cm polycarbonate cages (six mice per cage). The animals were assigned into either the control group (n = 12; six mice per sex) or fructose intervention group (n = 12; six mice per sex). After a week of acclimation, the fructose group was subjected to 34% fructose in deionized water (wt:vol) over six weeks to induce NAFLD conditions as previously described.11 To note, compared to conventional sugary beverages (e.g., soft drinks), the supplementation level of fructose is higher (11% vs. 34%) to induce liver damage markers within a reasonable intervention time range (i.e., 6 weeks).

Four-week-old male and female C57BL/6N mice were obtained from the Central Lab Animal Inc. (Seoul, South Korea) and housed in 42 x 27 x 15 cm polycarbonate cages (six mice per cage). The animals were assigned into either the control group (n = 12; six mice per sex) or fructose intervention group (n = 12; six mice per sex). After a week of acclimation, the fructose group was subjected to 34% fructose in deionized water (wt:vol) over six weeks to induce NAFLD conditions as previously described.11 To note, compared to conventional sugary beverages (e.g., soft drinks), the supplementation level of fructose is higher (11% vs. 34%) to induce liver damage markers within a reasonable intervention time range (i.e., 6 weeks).

The male C57BL/6J mice (6-8 weeks, Beijing Vital River Laboratory Animal Technology Co., Ltd., China) were exposed to 12 h of light and darkness at temperature (22 ± 2 ), humidity (55%) with free access to water and food. All the mice were acclimated for 1 week before the experiment, then the mice were fed normal chow diet (NCD) and high-fat diet (HFD, D12492) for 12 weeks. The HFD group was divided into 3 groups (HFD, low dose of DA (DA-L, 10 mg/kg/d), high dose of DA (DA-H, 20 mg/kg/d),n = 8)). DA was administered by gavage for 9 weeks, and 0.5% CMC-Na was administered by NCD and HFD.

Male 8-week-old C57/BL6 ApoE-/-mice of weight (22~25 g) were purchased from Changzhou Cavens experimental animal Co., Ltd (Jiangsu, China). After 5 weeks of feeding, HFD-fed mice were randomly assigned into 4 groups (n = 10) : HFD group (0.9 % sodium chloride by gavage), GB-L group (at a high dose of 20 mg kg-1d-1 GB in 0.9 % sodium chloride by gavage), GB-H group (at a high dose of 30 mg kg-1d-1 GB in 0.9 % sodium chloride by gavage), and Ato group (1.3 mg kg-1d-1 Ato in 0.9 % sodium chloride by gavage) as a positive control. The mice in ND group were given the same volume of 0.9 % sodium chloride.

Adult male Sprague-Dawley rats (300 g-350 g, specific pathogen free) were obtained from Institute of Genome Engineered Animal Models for Human Disease of Dalian Medical University (Dalian, China). To explore the influence of NaAsO2 (CAS No.7784-46-5, Sigma-Aldrich, USA) on the liver, the rats were subjected to NaAsO2 at the dosage of 0, 2.5, and 5 mg/kg by gavage for 9 months. The control group was gavaged with distilled water as vehicle.

Adult male Sprague-Dawley rats (300 g-350 g, specific pathogen free) were obtained from Institute of Genome Engineered Animal Models for Human Disease of Dalian Medical University (Dalian, China). To explore the influence of NaAsO2 (CAS No.7784-46-5, Sigma-Aldrich, USA) on the liver, the rats were subjected to NaAsO2 at the dosage of 0, 2.5, and 5 mg/kg by gavage for 9 months. The control group was gavaged with distilled water as vehicle.

After adaptive feeding, mice were randomly assigned to five groups (n = 10 per group). The details of the groups are as follows: 1) the normal diet (ND) group in which mice were fed ND (18% calories from fat); 2) the HFD group in which mice were fed HFD (60% calories from fat); 3) the HFD-EGCG/L group in which mice received 20 mg/kgbw EGCG by oral gavage daily during HFD feeding; 4) the HFD-EGCG/H group in which mice received 100 mg/kgbw EGCG by oral gavage daily during HFD feeding; and 5) the HFD-Fer-1 group in which mice received intraperitoneal injection of Fer-1 at 1 mg/kg. bw every 3 days during HFD feeding. Mice in the EGCG treatment groups were supplemented with EGCG (20 and 100 mg/kgbw) for 12 weeks. Meanwhile, mice in the ND group and the HFD group were orally gavaged with deionized water daily.

After adaptive feeding, mice were randomly assigned to five groups (n = 10 per group). The details of the groups are as follows: 1) the normal diet (ND) group in which mice were fed ND (18% calories from fat); 2) the HFD group in which mice were fed HFD (60% calories from fat); 3) the HFD-EGCG/L group in which mice received 20 mg/kgbw EGCG by oral gavage daily during HFD feeding; 4) the HFD-EGCG/H group in which mice received 100 mg/kgbw EGCG by oral gavage daily during HFD feeding; and 5) the HFD-Fer-1 group in which mice received intraperitoneal injection of Fer-1 at 1 mg/kg. bw every 3 days during HFD feeding. Mice in the EGCG treatment groups were supplemented with EGCG (20 and 100 mg/kgbw) for 12 weeks. Meanwhile, mice in the ND group and the HFD group were orally gavaged with deionized water daily.

After adaptive feeding, mice were randomly assigned to five groups (n = 10 per group). The details of the groups are as follows: 1) the normal diet (ND) group in which mice were fed ND (18% calories from fat); 2) the HFD group in which mice were fed HFD (60% calories from fat); 3) the HFD-EGCG/L group in which mice received 20 mg/kgbw EGCG by oral gavage daily during HFD feeding; 4) the HFD-EGCG/H group in which mice received 100 mg/kgbw EGCG by oral gavage daily during HFD feeding; and 5) the HFD-Fer-1 group in which mice received intraperitoneal injection of Fer-1 at 1 mg/kg. bw every 3 days during HFD feeding. Mice in the EGCG treatment groups were supplemented with EGCG (20 and 100 mg/kgbw) for 12 weeks. Meanwhile, mice in the ND group and the HFD group were orally gavaged with deionized water daily.

Eight-week-old C57BL/6 mice, body weight about 22-24 g, male (n = 24) were purchased from Beijing Vital River Laboratory Animal Technology Co. Ltd China. The mice were randomly divided into four groups and were maintained on a MCD diet (Medicience, Yangzhou, China) for 4, 8, and 12 weeks to induce NASH. Liver tissue and blood samples (from the eyeballs of the mice) were harvested for further analyses. Mice on a normal diet were used as the control.

Six-week-old male C57BL/6 mice were purchased from the Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). All of the mice were fed either a standard chow diet (SCD) (containing 62.2% carbohydrate, 24.6% protein, and 13.2% fat) or only a methionine-choline deficient diet (MCD) (containing 20% carbohydrate, 20% protein, and 60% fat) for 8 wk.

The 42 Specified Pathogen Free (SPF)-grade Sprague Dawley (SD) male rats with weighing (180 ± 20) g were purchased from Changsha Tianqin Experimental Animal Center. All rat were randomly divided into seven groups (6 rat per group) using a random number table. Rats were deeply anesthetized with chloral hydrate (0.5 ml/kg) and killed at the end of the experiment, after 8 weeks of modeling and 4 weeks of drug treatment.

The 42 Specified Pathogen Free (SPF)-grade Sprague Dawley (SD) male rats with weighing (180 ± 20) g were purchased from Changsha Tianqin Experimental Animal Center. All rat were randomly divided into seven groups (6 rat per group) using a random number table. Rats were deeply anesthetized with chloral hydrate (0.5 ml/kg) and killed at the end of the experiment, after 8 weeks of modeling and 4 weeks of drug treatment.