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

Pflugers Arch. 2018 Jun;470(6):867-881. doi: 10.1007/s00424-018-2117-0. Epub 2018 Feb 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / administration & dosage
  • Angiotensin I / therapeutic use*
  • Animals
  • Anti-Obesity Agents / administration & dosage
  • Anti-Obesity Agents / therapeutic use*
  • Diet, High-Fat / adverse effects
  • Infusions, Intraventricular
  • Male
  • Obesity / drug therapy
  • Obesity / etiology
  • Obesity / prevention & control*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley


  • Anti-Obesity Agents
  • Peptide Fragments
  • Angiotensin I
  • angiotensin I (1-7)