Research Article Details
| Article ID: | A10234 |
| PMID: | 31419466 |
| Source: | Mol Cell Endocrinol |
| Title: | Empaglifozin mitigates NAFLD in high-fat-fed mice by alleviating insulin resistance, lipogenesis and ER stress. |
| Abstract: | AIM: To evaluate the pleiotropic effects of empagliflozin in the liver through lipogenesis, beta-oxidation, and endoplasmic reticulum stress pathways. METHODS: Male C57Bl/6 mice, 3 months of age, received a control diet (C, 10% lipids, n = 20) or high-fat diet (HF, 50% lipids, n = 20) for 10 weeks, after that, the groups were subdivided to receive empagliflozin, during 5 weeks at a dose of 10 mg/kg/day added to the diets, totalizing four groups: C, C-EMPA, HF, and HF-EMPA. We performed biochemical analyzes, oral glucose tolerance test, homeostasis model assessment of insulin resistance (HOMA-IR), indirect calorimetry, liver stereology, western blotting, RT-qPCR for genes related to beta-oxidation, lipogenesis, and endoplasmic reticulum stress. RESULTS: After the treatment with empagliflozin, there was a 4% increase in energy expenditure, a 5% reduction in body mass, improvement in glucose tolerance and insulin sensitivity and insulin resistance. The expression of Ppar alpha was greater in the HF-EMPA group with a concomitant reduction in the expression of the lipogenic genes Fas, Srebp1c and Ppar gamma, according to protein expression. In addition, HF-EMPA showed a reduction in the genes related to endoplasmic reticulum stress Chop, Atf4, and Gadd45. CONCLUSION: Empagliflozin mitigates the development of NAFLD, confirmed through reduced expression of the genes involved in hepatic lipogenesis and genes involved in endoplasmic reticulum stress. Thus, empagliflozin may be an important tool to treat the progression of hepatic steatosis. |
| DOI: | 10.1016/j.mce.2019.110539 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D122 | Empagliflozin | Chemical drug | DB09038 | SLC5A2 inhibitor; SGLT-2 inhibitor | Improve insulin resistance | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |