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Background and Purpose Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin‐(1‐7) is a metabolite of angiotensin I and of angiotensin II . As an agonist of Mas receptors, angiotensin‐(1‐7) has beneficial cardiovascular and metabolic effects. Experimental Approach We investigated the anti‐obesity effects of transgenically overexpressed angiotensin‐(1‐7) in rats. We secondly examined whether weight loss due to telmisartan (8 mg·kg−1·d−1) in diet‐induced obese Sprague Dawley (SD) rats can be blocked when the animals were co‐treated with the Mas receptor antagonist A779 (24 or 72 μg·kg−1·d−1). Key Results In contrast to wild‐type controls, transgenic rats overexpressing angiotensin‐(1‐7) had 1.) diminished body weight when they were regularly fed with chow; 2.) were protected from developing obesity although they were fed with cafeteria diet (CD); 3.) showed a reduced energy intake that was mainly related to a lower CD intake; 5.) remained responsive to leptin despite chronic CD feeding; 6.) had a higher, strain‐dependent energy expenditure, and 7.) were protected from developing insulin resistance despite CD feeding. Telmisartan‐induced weight loss in SD rats was partially antagonized after a high, but not a low dose of A779. Conclusions and Implications Angiotensin‐(1‐7) regulated food intake and body weight and contributed to the weight loss after AT1 receptor blockade. Angiotensin‐(1‐7)‐like agonists may be drug candidates for treating obesity.

Background and Purpose AT1 receptor antagonists decrease body weight gain in models of murine obesity. However, fewer data are available concerning the anti‐obesity effects of these antagonists, given as a treatment after obesity had been established. Experimental Approach In spontaneously hypertensive rats, obesity was established by cafeteria diet (CD) feeding for 19 weeks. Rats were then were treated with telmisartan (8 mg·kg−1·d−1) or amlodipine (10 mg·kg−1·d−1; serving as blood pressure control) or telmisartan + amlodipine (2 + 10 mg·kg−1·d−1; to control for dose‐dependency) for 17 weeks. Rats receiving only chow (Cchow) or CD‐fed rats treated with vehicle (CCD) served as controls. Key Results The CD feeding induced obesity, hyperphagia, hyperlipidaemia, and leptin and insulin resistance. Telmisartan reduced the CD‐induced increase in body weight and abdominal fat mass. Whereas energy intake was higher rather than lower, the respiratory ratio was lower. After telmisartan, leptin‐induced energy intake was reduced and respiratory ratio was increased compared with CCD rats. Telmisartan also decreased plasma levels of triglycerides, free fatty acids and low‐density lipoprotein. Amlodipine alone or the combination telmisartan + amlodipine did not affect body weight and eating behaviour. Telmisartan, but not amlodipine and telmisartan + amlodipine, improved glucose utilization. The decrease in BP reduction was almost the same in all treatment groups. Conclusions and Implications Telmisartan exerted anti‐obesity effects and restored leptin sensitivity, given as a treatment to rats with obesity. Such effects required high doses of telmisartan and were independent of the decrease in blood pressure.