Research Article Details
| Article ID: | A09771 |
| PMID: | 31616384 |
| Source: | Front Endocrinol (Lausanne) |
| Title: | Inhibiting Ceramide Synthesis Attenuates Hepatic Steatosis and Fibrosis in Rats With Non-alcoholic Fatty Liver Disease. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic disorder diseases, which include a histological spectrum of conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Dysregulated metabolism of sphingomyelin in the liver plays a critical role in the pathogenesis of NAFLD. Ceramides are central molecules of sphingolipid biosynthesis and catabolism and play an important role in insulin resistance, apoptosis, and inflammation. In addition, apoptosis is a main contributor to the development of NAFLD. This study detected whether the inhibition of ceramide synthesis ameliorated hepatic steatosis and fibrosis in rats with NAFLD. Sprague-Dawley rats were used to establish the NAFLD model. Here, we showed that hepatic ceramide, steatosis, and fibrosis increased in liver tissue from rats with NAFLD. Chronic treatment with myriocin inhibited ceramide and lipid accumulation and improved fibrosis in liver tissue samples of high fat diet (HFD)-fed rats. In addition, hepatic inflammation and apoptosis were markedly ameliorated in HFD-fed rats treated with myriocin. Furthermore, myriocin treatment regulated the expression of pro-apoptosis and anti-apoptosis proteins by inactivating the c-Jun N-terminal kinase (JNK) signaling pathway in the liver of HFD-fed rats. Collectively, ceramide plays an important role in the pathogenesis of NASH and may represent a potential therapeutic strategy to prevent NAFLD. |
| DOI: | 10.3389/fendo.2019.00665 |
| 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 |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | 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 |