Empagliflozin Improves Metabolic and Hepatic Outcomes in a Non-Diabetic Obese Biopsy-Proven Mouse Model of Advanced NASH
| Autor: | Nikolaos Perakakis, Christos S. Mantzoros, Pavlina Chrysafi, Michael Feigh, Sanne Skovgård Veidal |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Biopsy Mice Obese Type 2 diabetes SGLT2 0302 clinical medicine Glucosides Non-alcoholic Fatty Liver Disease steatosis Homeostasis Medicine Glucose homeostasis Biology (General) Spectroscopy diabetes Fatty liver NASH General Medicine Computer Science Applications Chemistry Body Composition medicine.medical_specialty QH301-705.5 Lactosylceramides 030209 endocrinology & metabolism liver digestive system Article Catalysis Inorganic Chemistry 03 medical and health sciences Antigens CD Diabetes mellitus Internal medicine NAFLD Empagliflozin Animals Benzhydryl Compounds Physical and Theoretical Chemistry QD1-999 Molecular Biology Triglycerides business.industry Body Weight Organic Chemistry nutritional and metabolic diseases medicine.disease Mice Inbred C57BL Disease Models Animal Glucose 030104 developmental biology Endocrinology lipidomics Liver function Insulin Resistance Steatosis Steatohepatitis business |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 12 International Journal of Molecular Sciences, Vol 22, Iss 6332, p 6332 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22126332 |
| Popis: | Empagliflozin, an established treatment for type 2 diabetes (T2DM), has shown beneficial effects on liver steatosis and fibrosis in animals and in humans with T2DM, non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). However, little is known about the effects of empagliflozin on liver function in advanced NASH with liver fibrosis and without diabetes. This study aimed to assess the effects of empagliflozin on hepatic and metabolic outcomes in a diet-induced obese (DIO) and insulin-resistant but non-diabetic biopsy-confirmed mouse model of advanced NASH. Male C57BL/6JRj mice with a biopsy-confirmed steatosis and fibrosis on AMLN diet (high fat, fructose and cholesterol) for 36-weeks were randomized to receive for 12 weeks: (a) Empagliflozin (10 mg/kg/d p.o.), or (b) vehicle. Metabolic outcomes, liver pathology, markers of Kupffer and stellate cell activation and lipidomics were assessed at the treatment completion. Empagliflozin did not affect the body weight, body composition or insulin sensitivity (assessed by intraperitoneal insulin tolerance test), but significantly improved glucose homeostasis as assessed by oral glucose tolerance test in DIO-NASH mice. Empagliflozin improved modestly the NAFLD activity score compared with the vehicle, mainly by improving inflammation and without affecting steatosis, the fibrosis stage and markers of Kupffer and stellate cell activation. Empagliflozin reduced the hepatic concentrations of pro-inflammatory lactosylceramides and increased the concentrations of anti-inflammatory polyunsaturated triglycerides. Empagliflozin exerts beneficial metabolic and hepatic (mainly anti-inflammatory) effects in non-diabetic DIO-NASH mice and thus may be effective against NASH even in non-diabetic conditions. |
| Databáze: | OpenAIRE |
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