Research Article Details
| Article ID: | A19622 |
| PMID: | 26450277 |
| Source: | Br J Nutr |
| Title: | 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 non-alcoholic 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. |
| DOI: | 10.1017/S0007114515003621 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T09 | Toll-like receptor 4 | TLR4 | antagonist | Membrane receptor | O00206 | TLR4_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |