Abstract
We recently showed that the antiobese efficacy of the AT1 receptor blocker telmisartan (TEL) is at least partially related to an Ang(1-7)-dependent mechanism. Ang(1-7) acts via Mas, thus raising the question of whether Mas-deficient (Mas-ko) mice are likewise predisposed to develop diet-induced obesity and, further, whether this can be prevented by TEL treatment. Mas-ko mice and FVB/N wild-type (wt) animals were treated with TEL (8 mg/kg/day) or vehicle while they were fed with high-fat diet (HFD) or chow. Mice were phenotyped regarding body weight, fat mass, insulin sensitivity, and leptin sensitivity. In response to HFD feeding, gain in body weight and impairment of leptin sensitivity were similar between wt and Mas-ko mice. TEL reduced body weight in both strains but effects were stronger in Mas-ko mice. TEL diminished fat mass and restored leptin sensitivity only in Mas-ko mice. Blood glucose was higher in wt than Mas-ko mice fed with HFD while not differing when they were fed with chow. Insulin challenge confirmed that wt mice became insulin resistant when fed with HFD while HFD feeding did not impair insulin sensitivity in Mas-ko mice. TEL had no further effect. Our findings on the influence of TEL on growth and metabolism in Mas-ko mice conflict with our previous findings in rats. We assume that the FVB/N background of the mice may partly explain these inconsistent data. Moreover, it also seems feasible that the MrgD receptor compensates for Mas deficiency.
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Acknowledgments
We thank Prof. Marcus Altfeld and Urte Matschl from the Heinrich Pette Institute, Hamburg, for the measurements with the luminex system. The authors gratefully acknowledge Sherryl Sundell for improving the English style.
Funding
Carla Dapper and Franziska Schuster were supported by a grant of the German Research Foundation to the Graduiertenkolleg 1957 “Adipocyte-Brain Crosstalk,” University of Lübeck. The study was supported by a grant of the German Centre for Cardiovascular Research (DZHK). Walter Raasch received Telmisartan from Boehringer Ingelheim Pharmaceuticals, Inc. (Ingelheim, Germany).
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CD, FS, IS, FV, NA, and LACS performed the research; WR, MB, and CD designed the research study; CD, FS, FV, NA, LACS, and WR analyzed the data; WR, MB, and CD wrote the paper.
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Dapper, C., Schuster, F., Stölting, I. et al. The antiobese effect of AT1 receptor blockade is augmented in mice lacking Mas. Naunyn-Schmiedeberg's Arch Pharmacol 392, 865–877 (2019). https://doi.org/10.1007/s00210-019-01643-0
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DOI: https://doi.org/10.1007/s00210-019-01643-0