Research Article Details
| Article ID: | A04192 |
| PMID: | 33721354 |
| Source: | Clin Exp Pharmacol Physiol |
| Title: | Sodium butyrate ameliorates non-alcoholic fatty liver disease by upregulating miR-150 to suppress CXCR4 expression. |
| Abstract: | Sodium butyrate (NaB) in the gut of animals possesses the potential to modulate lipid metabolism, regulate innate immunity and protect intestinal health. Accumulating data have supported the important function of metabolites of intestinal microflora (MIM) in non-alcoholic fatty liver disease (NAFLD). This study intended to investigate the role of NaB in NAFLD and its specific mechanism. Mice were fed a high-fat diet (HFD) for 16 weeks to establish the NAFLD mouse model. The mice were intragastrically administrated MIM (200 µL/day) or NaB (200 mg/kg/day) by gavage for another 8 weeks. The morphology of liver tissues was observed by hematoxylin and eosin (H&E) staining, and the lipid deposition of liver tissues was examined by oil red O staining. The NAFLD cell model was constructed in alpha mouse liver 12 (AML12) cells by 24 hours of stimulation with 0.5 mM free fatty acids. After treatment with 10 mM NaB, AML12 cells were transfected with mimic-miR-150 or inhibitor-miR-150. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure the contents of interleukin 1β (IL-1β), IL-6 and tumour necrosis factor α (TNF-α) and the expression of microRNA (miR)-150 and CXCR4 in liver tissues of mice and in AML12 cells. A luciferase reporter assay was applied to verify the binding relationship between miR-150 and CXCR4. The H&E and oil red O staining results showed hepatic steatosis in the liver tissues of HFD-fed mice. There were elevated contents of triacylglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose, enhanced activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST), increased homeostatic model assessment of insulin resistance scores and increased inflammatory responses in the serum of HFD-fed mice. However, intervention with MIM or NaB reversed the above trends, indicating that MIM or NaB intervention relieved hepatic steatosis in mice. HFD-fed mice had downregulated expression of miR-150, whereas the expression level was upregulated after MIM or NaB treatment. Sodium butyrate attenuated NAFLD progression by regulating miR-150. MiR-150 can negatively target CXCR4. Sodium butyrate mitigates HFD-induced NAFLD in mice by upregulating miR-150 expression to downregulate CXCR4. |
| DOI: | 10.1111/1440-1681.13497 |
| 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 | |
|---|---|---|---|---|---|---|---|
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |