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Published on: May 26, 2022
Angiotensin II receptor blockers downsize adipocytes in spontaneously type 2 diabetic rats with visceral fat obesity
Yutaka Mori1, Yohta Itoh, Naoko Tajima
1Department of Internal Medicine, National Hospital Organization, Utsunomiya National Hospital, Kawachi-gun, Tochigi, Japan. moriyutakajp@yahoo.com
Objective:
To investigate the influence of blockade of the renin-angiotensin system (RAS) on adipocytes, we compared the effect of telmisartan versus valsartan and amlodipine on adipocyte cellularity in the spontaneously type 2 diabetic, obese rat model.
Methods:
Male Otsuka Long Evans Tokushima Fatty rats, 8-week-old, were divided into four groups as follows: valsartan (V) group (10 mg/kg, n = 12), telmisartan (T) group (5 mg/kg, n = 12), amlodipine (A) group (2 mg/kg, n = 12), and control (C) group (n = 12). Each drug was mixed with chow and given for 16 weeks.
Results:
Although no significant differences were observed in the fasting plasma glucose level between the groups, the fasting plasma insulin level for group T was significantly lower than that for group C. Histopathologic examination showed that the ratio of small adipocytes in groups V and T was significantly higher than that in group C, with the ratio of large adipocytes and the mean adipocyte size shown to be significantly lower in groups V and T than in group C. Furthermore, group T was shown to have a significantly higher ratio of small adipocytes, a significantly lower ratio of large adipocytes, as well as a significantly lower mean adipocyte size, compared to group V.
Conclusions:
Although both valsartan and telmisartan downsized adipocytes, adipocyte downsizing was significantly greater with telmisartan compared to valsartan. The likely mechanism for this difference was thought to be the PPAR-gamma-mediated action of telmisartan.
Insights
Telmisartan and valsartan reduced adipocyte size in diabetic rats. Telmisartan demonstrated a greater effect on adipocyte downsizing, likely due to PPAR-gamma activation.
Area of Science:
- Endocrinology
- Pharmacology
- Metabolic Research
Background:
- The renin-angiotensin system (RAS) plays a role in metabolic regulation.
- Adipocyte size and number are critical in obesity and type 2 diabetes.
Purpose of the Study:
- To compare the effects of telmisartan and valsartan on adipocyte cellularity.
- To investigate the influence of renin-angiotensin system (RAS) blockade on adipocytes in a type 2 diabetic rat model.
Main Methods:
- Otsuka Long Evans Tokushima Fatty rats were treated with valsartan, telmisartan, or amlodipine for 16 weeks.
- Adipocyte cellularity was assessed via histopathologic examination.
- Fasting plasma glucose and insulin levels were measured.
Main Results:
- Telmisartan significantly reduced fasting insulin levels compared to controls.
- Both valsartan and telmisartan decreased the ratio of large adipocytes and mean adipocyte size.
- Telmisartan showed a more pronounced reduction in large adipocytes and mean adipocyte size than valsartan.
Conclusions:
- Telmisartan and valsartan effectively reduce adipocyte size in this model.
- Telmisartan exhibits superior adipocyte downsizing effects compared to valsartan.
- Peroxisome proliferator-activated receptor gamma (PPAR-gamma) activation is a potential mechanism for telmisartan's enhanced effect.
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