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

  • Martina Winkler
  • Michael Bader
  • Franziska Schuster
  • Ines Stölting
  • Sonja Binder
  • Walter RaaschEmail author
Integrative Physiology
Part of the following topical collections:
  1. Integrative Physiology

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 

Abbreviations

AngII

Angiotensin II

AngI

Angiotensin I

Ang(1–7)

Angiotensin-(1–7)

AOGEN

Angiotensinogen

ARB

AT1 receptor blocker

AT1 receptor

Angiotensin II type 1 receptor

AUC

Area under the curve

BBB

Blood-brain barrier

BMI

Body mass index

Bw

Body weight

CD

Cafeteria diet

Cmax

Maximal concentration

EDTA

Ethylenediaminetetraacetic acid

GFAP

Glial fibrillary acidic protein

HDL

High-density lipoproteins

HPA axis

Hypothalamic-pituitary-adrenal axis

Ko

Knock out

LepR

Leptin receptor

LRT

Leptin resistance test

MRI

Magnetic resonance imaging

OGTT

Oral glucose tolerance test

POMC

Proopiomelanocortin

PPARγ

Peroxisome proliferator-activated receptor delta

PPARδ

Peroxisome proliferator-activated receptor gamma

RAS

Renin-angiotensin system

RER

Respiratory exchange rate

SBP

Systolic blood pressure

SD

Sprague Dawley rat

TEL

Telmisartan

TG

Transgenic rat

T2DM

Type 2 diabetes mellitus

Notes

Acknowledgments

MW, MB, FS, IS, SB, and WR performed the research, WR, MW, and MB designed the research study, WR and MW analyzed the data, and WR, MW, and MB wrote the paper. The authors gratefully acknowledge Sherryl Sundell for improving the English style.

Source(s) of funding

Martina Winkler received funding from the Konrad Adenauer Stiftung (Germany). Franziska Schuster was 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).

Compliance with ethical standards

Conflict(s) of interest/disclosure(s)

No conflict of interests

Supplementary material

424_2018_2117_MOESM1_ESM.docx (257 kb)
ESM 1 (DOCX 256 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Martina Winkler
    • 1
  • Michael Bader
    • 2
    • 3
    • 4
    • 5
    • 6
  • Franziska Schuster
    • 1
    • 7
  • Ines Stölting
    • 1
  • Sonja Binder
    • 1
  • Walter Raasch
    • 1
    • 7
    • 8
    Email author
  1. 1.Institute of Experimental and Clinical Pharmacology and ToxicologyUniversity of LübeckLübeckGermany
  2. 2.National Institute of Science and Technology in Nanobiopharmaceutics, Department of Physiology and Biophysics, Institute of Biological SciencesFederal University of Minas GeraisBelo HorizonteBrazil
  3. 3.Max-Delbrück-Center for Molecular Medicine (MDC)BerlinGermany
  4. 4.DZHK (German Centre for Cardiovascular Research)partner site BerlinGermany
  5. 5.Center for Structural and Cell Biology in Medicine, Institute for BiologyUniversity of LübeckLübeckGermany
  6. 6.Charité – University Medicine BerlinBerlinGermany
  7. 7.CBBM (Center of Brain, Behavior and Metabolism)LübeckGermany
  8. 8.DZHK (German Centre for Cardiovascular Research)LübeckGermany

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