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Chronic blockade of angiotensin AT 1 receptors improves cardinal symptoms of metabolic syndrome in diet‐induced obesity in rats
Author(s) -
MüllerFielitz Helge,
Hübel Nils,
Mildner Martin,
Vogt Florian M,
Barkhausen Jörg,
Raasch Walter
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12510
Subject(s) - telmisartan , endocrinology , medicine , amlodipine , leptin , blood pressure , losartan , metabolic syndrome , angiotensin ii , obesity
Background and Purpose AT 1 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 ( C chow ) or CD ‐fed rats treated with vehicle ( C CD ) 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 C CD 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.