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Development of obesity can be prevented in rats by chronic icv infusions of AngII but less by Ang(1-7)

Item Type:Article
Title:Development of obesity can be prevented in rats by chronic icv infusions of AngII but less by Ang(1-7)
Creators Name:Winkler, M. and Bader, M. and Schuster, F. and Stölting, I. and Binder, S. and Raasch, W.
Abstract:Considering that obesity is one of the leading risks for death worldwide, it should be noted that a brain-related mechanism is involved in AngII-induced and AT1-receptor-dependent weight loss. It is moreover established that activation of the Ang(1-7)/ACE2/Mas axis reduces weight, but it remains unclear whether this Ang(1-7) effect is also mediated via a brain-related mechanism. Additionally to Sprague Dawley (SD) rats, we used TGR(ASrAOGEN) selectively lacking brain angiotensinogen, the precursor to AngII, as we speculated that effects are more pronounced in a model with low brain RAS activity. Rats were fed with high-calorie cafeteria diet. We investigated weight regulation, food behavior, and energy balance in response to chronic icv.-infusions of AngII (200 ng*h(-1)), or Ang(1-7) (200/600 ng*h(-1)) or artificial cerebrospinal fluid. High- but not low-dose Ang(1-7) slightly decreased weight gain and energy intake in SD rats. AngII showed an anti-obese efficacy in SD rats by decreasing energy intake and increasing energy expenditure and also improved glucose control. TGR(ASrAOGEN) were protected from developing obesity. However, Ang(1-7) did not reveal any effects in TGR(ASrAOGEN) and those of AngII were minor compared to SD rats. Our results emphasize that brain AngII is a key contributor for regulating energy homeostasis and weight in obesity by serving as a negative brain-related feedback signal to alleviate weight gain. Brain-related anti-obese potency of Ang(1-7) is lower than AngII but must be further investigated by using other transgenic models as TGR(ASrAOGEN) proved to be less valuable for answering this question.
Keywords:Angiotensin II, Angiotensin (1-7), Brain, Glycemic Control, Insulin Resistance, Obesity, Animals, Rats
Source:Pflugers Archiv
ISSN:0031-6768
Publisher:Springer
Volume:470
Number:6
Page Range:867-881
Date:June 2018
Official Publication:https://doi.org/10.1007/s00424-018-2117-0
PubMed:View item in PubMed

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