Research Article Details
| Article ID: | A16180 |
| PMID: | 28515456 |
| Source: | Sci Rep |
| Title: | Metabolomic analysis shows differential hepatic effects of T2 and T3 in rats after short-term feeding with high fat diet. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible. Our results showed that both T2 and T3 strongly induced autophagy and intra-hepatic acylcarnitine flux but prevented the generation of sphingolipid/ceramides in animals fed HFD. Interestingly, although both T2 and T3 decreased hepatic fat content, only T2 was able to rescue the impairment in AKT and MAPK/ERK pathways caused by HFD. In summary, we have identified and characterized the effects of T2 and T3 on hepatic metabolism during short-term exposure to HFD. These findings illuminate the common and divergent metabolic pathways by T2 and T3 that also may be important in the prevention and treatment of NAFLD. |
| DOI: | 10.1038/s41598-017-02205-1 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| 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 |