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Angiotensin-II receptor antagonist alleviates non-alcoholic fatty liver in KKAy obese mice with type 2 diabetes
1Department of General Medicine, Kanazawa Medical University, Ishikawa, Japan.
Abstract:
We examined the effects of the angiotensin-II receptor antagonist candesartan on non-alcoholic fatty liver (NAFL) and circulating adiponectin concentrations in KKAy obese mice with type 2 diabetes mellitus. The KKAy mice were randomly assigned to receive either candesartan at a once-daily dose of 10 mg/kg (n = 5) or placebo (n = 5). The differences in liver weight, histological evaluation of hepatic lipid infiltration, serum adiponectin concentration and hepatic adiponectin mRNA levels between the two groups were determined on day 7 after treatment was initiated. Candesartan-treated mice demonstrated significantly lower liver weights and reduced lipid droplets in hepatic cells compared with control mice. The circulating adiponectin levels and hepatic expression of adiponectin mRNA were significantly higher in candesartan-treated mice than control mice. These results suggest that candesartan might alleviate NAFL through elevation of circulating adiponectin levels in KKAy obese mice with type 2 diabetes mellitus.
Insights
Candesartan treatment significantly reduced non-alcoholic fatty liver (NAFL) and increased adiponectin levels in obese mice with type 2 diabetes. This suggests candesartan may be a potential therapeutic for NAFL by boosting adiponectin.
Area of Science:
- Metabolic disorders
- Pharmacology
- Hepatology
Background:
- Non-alcoholic fatty liver (NAFL) is a growing health concern, particularly in individuals with obesity and type 2 diabetes.
- Adiponectin, a key adipokine, plays a crucial role in regulating glucose and lipid metabolism and is often found at lower levels in NAFL patients.
Purpose of the Study:
- To investigate the therapeutic potential of candesartan, an angiotensin-II receptor antagonist, in ameliorating NAFL.
- To determine the effect of candesartan on circulating adiponectin levels and hepatic adiponectin mRNA expression in a mouse model of type 2 diabetes and obesity.
Main Methods:
- KKAy obese mice with type 2 diabetes were randomly assigned to receive either candesartan (10 mg/kg/day) or a placebo for 7 days.
- Evaluated liver weight, hepatic lipid infiltration via histological analysis, serum adiponectin concentrations, and hepatic adiponectin mRNA levels.
Main Results:
- Candesartan treatment resulted in significantly lower liver weights and reduced hepatic lipid droplets compared to the placebo group.
- Mice treated with candesartan exhibited significantly higher circulating adiponectin levels and increased hepatic adiponectin mRNA expression.
Conclusions:
- Candesartan demonstrates a potential to alleviate non-alcoholic fatty liver disease in obese mice with type 2 diabetes.
- The beneficial effects of candesartan on NAFL may be mediated through the elevation of circulating adiponectin levels and enhanced hepatic adiponectin expression.
