The metabolic syndrome (MS) is a risk of cardiovascular diseases and diabetes. While various pharmacological treatments have been used, the number of patients with MS has been increasing. We have demonstrated that mice lacking renin are lean (Cell Metab 2007). We therefore hypothesized that modulating the renin-angiotensin aldosterone system may be useful as a treatment of obesity and MS.
Design and Method:
Male mice 9–10 weeks of age lacking aldosterone synthase (AS KO) or wild type (WT) were fed a high-fat diet for 3 weeks. In another experiment C57BL/6J wild type male mice 9-weeks of age were randomly divided into two groups and given vehicle (control) or eplerenone (600 mg/kg/day) by gavage for 4 weeks. Both groups of mice were fed a high-fat diet for 4 weeks.
While body weight of WT mice increased from 23.0 ± 0.3 g to 26.3 ± 1.0 g (p < 0.01), that of AS KO mice did not significantly increase (from 20.1 ± 0.8 g to 21.1 ± 0.8 g, p = 0.43), suggesting that AS KO mice are resistant to diet-induced obesity. Body weight of control mice not treated with eplerenone increased from 24.0 ± 0.4 g to 27.0 ± 0.4 g (p < 0.01), whereas that of mice administered with eplerenone did not significantly increase (from 23.8 ± 0.4 g to 24.8 ± 0.3 g, p = 0.054). Mice administered with eplerenone were also resistant to diet-induced obesity and had low adipose tissue mass compared with controls despite similar food intake.
Aldosterone is a promising target of treatment of obesity. The mechanism of how eplerenone works is under investigation.