Losartan prevents body weight gain in diet induced obese rats

Abstract

The renin angiotensin system (RAS), best known for its involvement in the regulation of cardiovascular function and salt/water balance, has recently been suggested to play a role in the regulation of energy homeostasis as interference with systemic RAS activity has been shown to decrease body weight and fat. The present study was undertaken to determine whether losartan, a non‐peptide ATII Type 1 receptor blocker, would influence daily body weight gain in diet induced obese (DIO) rats.Male Sprague Dawley rats (125–150g) were exposed to either a HFD or fed standard rat chow. After 10 weeks, rats on HFD were divided into DIO or diet resistant (DR) and at 18 weeks, body weight, and food and water intake were measured daily for 5 weeks. After a 14 day control period, rats were administered losartan (30mg/kg) in drinking water for 14 days, followed by return to tap water for an additional 7 days and effects on body weight and food and water intake assessed.There was no difference in daily body weight gain during in the control period between chow fed (2.6±0.5g, n=8), DR (2.1±0.5g, n=8) or DIO rats (3.4±0.4g, n=8, p=.18, one way ANOVA). Although losartan treatment attenuated daily body weight gain in chow fed rats (1.25±0.5g, n=8), it completely abolished daily weight gain in DR (−0.65±0.3g, n=8) and DIO (−0.43±0.7g, n=8) rats. Upon return to normal tap water, all rats gained weight as they had prior to losartan administration (chow 3.3±0.2g, DR 2.9±0.5g, DIO 3.8±0.5g).Our data demonstrate that losartan attenuates body weight gain in rats fed either a HFD (DR and DIO) or chow diet, an effect which was more pronounced in animals fed the HFD. These data suggest that the RAS plays a role in body weight homeostasis and that pharmacological agents that interfere with the functioning of the RAS may have be useful in the treatment for obesity.