Empagliflozin Improves Metabolic and Hepatic Outcomes in a Non-Diabetic Obese Biopsy-Proven Mouse Model of Advanced NASH
Abstract
:1. Introduction
2. Results
2.1. Empagliflozin Has No Major Effect on Body Weight or Body Composition in DIO-NASH Mice
2.2. Empagliflozin Improves Glucose Homeostasis Without Affecting Insulin Sensitivity in DIO-NASH Mice
2.3. Empagliflozin Improves Histopathological NAFLD Activity Score (NAS) But Not Fibrosis Stage In DIO-NASH Mice
2.4. Empagliflozin Reduces Lactosylceramides and Increases Unsaturated Triglycerides
3. Discussion
4. Methods
4.1. Study Design
4.2. Biochemical Measurements and Tolerance Tests
4.3. Liver Pathology and Immunohistochemistry (IHC) Staining
4.4. EchoMRI Body Composition
4.5. Lipidomics
4.6. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
a-SMA | Alpha-smooth muscle actin |
ALT | Alanine aminotransferase |
AST | Aspartate aminotransferase |
CAP | Controlled attenuation parameter |
Col1a1 | Collagen 1a1 |
GLP-1 | Glucagon-like peptide 1 |
H&E | Hematoxylin-eosin |
HOMA-IR | Homeostatic model assessment of insulin resistance |
IHC | Immunohistochemistry |
ipITT | Intraperitoneal insulin tolerance test |
KITT | Calculated plasma glucose disappearance rate |
NAFL | Non-alcoholic fatty liver |
NAFLD | Non-alcoholic fatty liver disease |
NAS | NAFLD activity score |
NASH | Non-alcoholic steatohepatitis |
OGTT | Oral glucose tolerance test |
PLS-DA | Partial least squares-discriminant analysis |
QUICKI | Quantitative insulin sensitivity check index |
RCT | Randomized controlled trial |
SGLT2i | Sodium-glucose cotransporter 2 inhibitors |
SPMs | Pro-resolving mediators |
T2DM | Type 2 diabetes mellitus |
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Perakakis, N.; Chrysafi, P.; Feigh, M.; Veidal, S.S.; Mantzoros, C.S. Empagliflozin Improves Metabolic and Hepatic Outcomes in a Non-Diabetic Obese Biopsy-Proven Mouse Model of Advanced NASH. Int. J. Mol. Sci. 2021, 22, 6332. https://doi.org/10.3390/ijms22126332
Perakakis N, Chrysafi P, Feigh M, Veidal SS, Mantzoros CS. Empagliflozin Improves Metabolic and Hepatic Outcomes in a Non-Diabetic Obese Biopsy-Proven Mouse Model of Advanced NASH. International Journal of Molecular Sciences. 2021; 22(12):6332. https://doi.org/10.3390/ijms22126332
Chicago/Turabian StylePerakakis, Nikolaos, Pavlina Chrysafi, Michael Feigh, Sanne Skovgard Veidal, and Christos S. Mantzoros. 2021. "Empagliflozin Improves Metabolic and Hepatic Outcomes in a Non-Diabetic Obese Biopsy-Proven Mouse Model of Advanced NASH" International Journal of Molecular Sciences 22, no. 12: 6332. https://doi.org/10.3390/ijms22126332