Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 396, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2020.114997
Keywords
Insulin Resistance; Dapagliflozin; Statins; Renal Lipotoxicity; Liver Steatosis
Categories
Funding
- Thailand Research Fund [RSA6080015]
- Royal Golden Jubilee PhD program [PhD/0063/2560]
- Faculty of Medicine Research Fund, Chiang Mai University [058-2563]
- Graduate Research Scholarship Chiang Mai University
- Functional Food Research Center for Well-being, Chiang Mai University
- Chiang Mai University
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High-fat high-fructose diet (HFF) in obesity can induce dyslipidemia and lipid accumulation both in kidney and liver which related to insulin resistance and lipotoxicity-induced cellular damage. We investigated whether dapagliflozin with or without atorvastatin could improve lipid accumulation-induced kidney and liver injury in HFF-induced insulin resistant rats. Male Wistar rats were fed with HFF for 16 weeks and then received drug treatments for 4 weeks; vehicle, dapagliflozin, atorvastatin and dapagliflozin plus atorvastatin treatment groups. HFF rats demonstrated insulin resistance, dyslipidemia, liver injury and renal dysfunction associated with impaired renal lipid metabolism and lipid accumulation. Dapagliflozin and combination treatment could improve HFF-induced insulin resistance, lipogenesis and lipotoxicity-related renal oxidative stress, inflammation, fibrosis and apoptosis leading to kidney dysfunction recovery. Liver injury-associated inflammation was also improved by these two regimens. Notably, the reduced lipid accumulation in liver and kidney that linked to an improvement of lipid oxidation was prominent in the combination treatment. Therefore, dapagliflozin combined with atorvastatin treatment exert the beneficial effects on lipid metabolism and lipotoxicity in liver and kidney injury via the attenuation of oxidative stress, fibrosis and apoptosis in insulin resistant model.
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