Supplementation of sodium butyrate protects mice from the development of non-alcoholic steatohepatitis (NASH)

Abstract

Overnutrition, insulin resistance and an impaired intestinal barrier function are discussed as critical factors in the development of nonalcoholic fatty liver disease. Not only butyrate-producing probiotics as well as supplementation of sodium butyrate (SoB) have been suggested to bear protective effects on liver damage of various aetiologies. However, whether an oral consumption of SoB has a protective effect on Western-style diet (WSD)-induced non-alcoholic steatohepatitis (NASH) and if so molecular mechanism involved has not yet been determined. Eight-week-old C57BL/6J mice were pair-fed either a liquid control or WSD ± 0·6 g/kg body weight SoB. After 6 weeks, markers of liver damage, inflammation, toll-like receptor (TLR)-4 signalling, lipid peroxidation and glucose as well as lipid metabolism were determined in the liver tissue. Tight junction protein levels were determined in the duodenal tissue. SoB supplementation had no effects on the body weight gain or liver weight of WSD-fed mice, whereas liver steatosis and hepatic inflammation were significantly decreased (e.g. less inflammatory foci and neutrophils) when compared with mice fed only a WSD. Tight junction protein levels in duodenum, hepatic mRNA expression of TLR-4 and sterol regulatory element-binding protein 1c were altered similarly in both WSD groups when compared with controls, whereas protein levels of myeloid differentiation primary response gene 88, inducible nitric oxide synthase, 4-hydroxynonenal protein adducts and F4/80 macrophages were only significantly induced in livers of mice fed only the WSD. In summary, these data suggest that an oral supplementation of SoB protects mice from inflammation in the liver and thus from the development of WSD-induced NASH.

Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota

“…The gut microbiota metabolite butyrate, which obviously increased after FMT intervention, is a pivotal immune regulator and anti-inflammatory substance. It improves the hepatic insulin resistance and attenuates HFD-induced steatohepatitis 23, 39–41 . In this study, the pro-inflammatory factors in the liver, such as TNF-α, MCP-1, IL-1 and IL-6, were decreased in the FMT-treated mice.…”

“…The improvement in hepatic steatosis may result from enhanced intrahepatic insulin sensitivity after FMT. Others showed that in mice with NASH, supplementation of sodium butyrate caused increased expression of insulin receptor in the liver, leading to improved liver insulin sensitivity and hepatic steatosis 41 . Here we also showed that in mice subjected to FMT, the protein level of insulin receptor was upregulated, following a significant increase of butyrate concentration in cecal content after FMT.…”

Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin

“…It has been reported that supplementation of butyrate producing probiotics improved the lipid profile and reduced the progression of obesity in mice [26]. Further, intervention of NaB reduced the development of non-alcoholic steatohepatitis (NASH) in C57BL/6J mice [37]. Tributyrin (a pro-drug of butyrate) also attenuates the obesity-associated inflammation and insulin-resistance in HFD fed mice [23].…”

Changes in the Intestinal Microbiome and Alcoholic and Nonalcoholic Liver Diseases: Causes or Effects?

“…Interestingly, simply adding butyrate to the diets of mice with steatosis reduced liver injury 70 . A meta-analysis found that this probiotic use can reduce serum levels of ALT and aspartate aminotransferase (AST), inflammation, and insulin resistance in NAFLD patients 71 .…”