Research Article Details
| Article ID: | A06578 |
| PMID: | 32821721 |
| Source: | J Lipid Atheroscler |
| Title: | Ceramides: Nutrient Signals that Drive Hepatosteatosis. |
| Abstract: | Ceramides are minor components of the hepatic lipidome that have major effects on liver function. These products of lipid and protein metabolism accumulate when the energy needs of the hepatocyte have been met and its storage capacity is full, such that free fatty acids start to couple to the sphingoid backbone rather than the glycerol moiety that is the scaffold for glycerolipids (e.g., triglycerides) or the carnitine moiety that shunts them into mitochondria. As ceramides accrue, they initiate actions that protect cells from acute increases in detergent-like fatty acids; for example, they alter cellular substrate preference from glucose to lipids and they enhance triglyceride storage. When prolonged, these ceramide actions cause insulin resistance and hepatic steatosis, 2 of the underlying drivers of cardiometabolic diseases. Herein the author discusses the mechanisms linking ceramides to the development of insulin resistance, hepatosteatosis and resultant cardiometabolic disorders. |
| DOI: | 10.12997/jla.2020.9.1.50 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D201 | L-Carnitine | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D062 | Carnitine complex | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |