Abstract
The gut-liver axis is one of the most emphasized topics in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Intestinal microbiota dysbiosis has been shown to be a predictor of disease severity and progression to fatty liver disease. Therefore, research addressing gut-based therapies has become popular. To investigate the effect of lactulose and polyethylene glycol 3350 (PEG 3350) in mice with induced obesity and NAFLD at a non-diarrheal dose. Thirty-six C57BL/6J male mice were divided into 6 groups. The first 2 groups (n = 6 each) were used as an induced obesity model (group A) and NAFLD model (group B) for 8 weeks. The remaining 24 animals were categorized into control diet group, high-fat diet (HFD) group, HFD + lactulose group, and HFD + PEG 3350 group. Serum and liver tissue samples were obtained for biochemical and histopathological analyses, respectively. The HFD + lactulose treatment group displayed a significant decrease in liver weight (1.3 (1.3-1.4) kg compared to 1.8 (1.6-1.9) kg) and NAFLD activity score (NAS) (1.5 (1.0-3.0) compared to 5.0 (4.0-5.0), respectively; p = 0.0043, p = 0.0021) when compared with the HFD group. However, a decrease in body weight (35.0 (34.6-36.0) kg compared to 40.9 (34.7-41.9) kg) and hepatosteatosis (HS) rate (33.3% compared to 100.0%) were not statistically significant (p = 0.1796, p = 0.0606, respectively). The HFD + PEG 3350 treatment group showed a statistically significant decrease in body weight (32.4 (30.2-33.9) kg compared to 40.9 (34.7-41.9) kg), liver weight (1.5 (1.3-1.5) kg compared to 1.8 (1.6-1.9) kg), HS rate (16.7% compared to 100.0%) and NAS (0.5 (0.0-1.0) compared to 5.0 (4.0-5.0); p = 0.0086, p = 0.0086, p = 0.0151, and p = 0.0021, respectively) when compared with the HFD group. We demonstrated that non-diarrheal dose of lactulose and PEG 3350 reduced hepatic inflammation in mice with induced NAFLD. It was also observed that PEG 3350 decreased HS and body weight. We believe these mechanisms can be utilized as novel therapeutic approaches in NAFLD in prospective human studies.
Highlights
The gut-liver axis is one of the most emphasized topics in the pathogenesis of non-alcoholic fatty liver disease (NAFLD)
The high-fat diet (HFD) + lactulose treatment group displayed a significant decrease in liver weight (1.3 (1.3– 1.4) kg compared to 1.8 (1.6–1.9) kg) and NAFLD activity score (NAS) (1.5 (1.0–3.0) compared to 5.0 (4.0–5.0), respectively; p = 0.0043, p = 0.0021) when compared with the HFD group
We demonstrated that non-diarrheal dose of lactulose and PEG 3350 reduced hepatic inflammation in mice with induced NAFLD
Summary
The gut-liver axis is one of the most emphasized topics in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease (NAFLD) is an everincreasing major public health problem worldwide, and due to the high rates of hepatitis B immunization and the introduction of the hepatitis C vaccine, likely the most common cause of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a histologically more aggressive subgroup of NAFLD and is more frequently associated with the development of fibrosis and cirrhosis. Mitochondrial dysfunction and the 2nd hit occurs, resulting in hepatocyte damage, inflammation and fibrosis.[2] the majority of NAFLD patients are overweight or obese, there is a subgroup of patients with normal body mass index (BMI); such situation is defined as lean NAFLD. Other factors in the pathogenesis besides insulin resistance, dyslipidemia and obesity are thought to be involved
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