Walter Raasch

Institute of Experimental and Clinical Pharmacology and Toxicology

Group Members

Walter Raasch (Group leader)
Gianna Huber (PhD student)
Viktorija Gustaityte (MD student)
Laura Beckmann (MD student)
Carla Dapper (MD student)
Elias Rawish (MD student)

Research Interests

In recent years, metabolic syndrome (MetS) has evolved into a problem of epidemic proportions in Western countries and associates obesity with numerous other abnormalities, including alterations in glucose metabolism, dyslipidemia and hypertension. Accumulating evidence suggests an activation of the renin-angiotensin-aldosterone-system (RAAS) in patients with MetS. Inhibition of the RAAS represents not only one established approach for lowering high blood pressure but also for treating other cardinal symptoms of MetS. Findings of our group support the broad efficacy of AT1-receptor blockers (ARBs) and ACE-inhibitors on hypertension, glucose utilization and the reactivity of the hypothalamus-pituitary-adrenal (HPA)-axis. We actually focus on antiobese actions of ARBs, in particular showing that reduction of body weight after AT1-blockade is related to a downregulation of orexigenic hypothalamic peptides, a reduction of food intake and an increase in energy expenditure. These antiobese effects of ARBs occurs 1.) only after high-dosing, 2.) independently on its antihypertensive potency and 3.) in a manner dependent on an intact leptin signaling. Current projects address the questions whether:

  • The leptin sensitivity is enhanced by ARBs for promoting antiobese effects;
  • The gut microbiome is involved in ARB-induced weight loss;
  • An Ang(1-7)/Mas dependent pathway is involved in weight regulation
  • Reduced weight gain after ARB treatment has to be attributed to a brain and/or fat tissue related mechanism.
  • The ARB-reduced weight loss is also related to an impaired drive of the HPA axis


Collaborations

  • Bader, Max-Delbrück-Center for Molecular Medicine (MDC), Berlin
  • Lars Kuerschner, LIMES-Institut, Universität Bonn
  • Stefan Dhein, Herzzentrum, Klinik für Herzchirurgie, Leipzig
  • William A. Banks, University of Washington, Seattle, USA
  • Robson A Santos, Federal University of Minas Gerais, Brazil


Latest Publications

  1. Winkler M, Schuchard J, Stölting I, Vogt FM, Barkhausen J, Thorns C, Bader M, Raasch W. The brain renin-angiotensin system plays a crucial role in regulating body weight in diet-induced rat obesity. Br J Pharmacol. 2016 Feb 19. doi: 10.1111/bph.13461. [Epub ahead of print]
  2. Blanke K, Schlegel F, Dhein S, Raasch W, Bader M, Dähnert I, Salameh A. Effect of angiotensin(1-7) on heart function in an experimental rat model of obesity. Front Physiol, 2015, 6:392, doi: 10.3389/fphys.2015.00392.
  3. Schuchard J, Winkler M, Stoelting I, Schuster F, Vogt F, Barkhausen J, Thorns C, Santos RA, Bader M, Raasch W. Prevention of weight gain after AT1 receptor blockade in diet-induced rat obesity is at least partially related to an angiotensin(1-7)/Mas-dependent mechanism. Br J Pharmacol, 2015, 72:3764-78
  4. Müller-Fielitz H, Lau M, Geißler C, Werner L, Winkler M, Raasch W. Preventing leptin resistance by blocking angiotensin II AT1 receptors in diet-induced obese rats. Br J Pharmacol, 2015, 172:857-68.
  5. Müller-Fielitz H, Hübel N, Mildner M, Vogt FM, Barkhausen J, Raasch W. Chronic blockade of angiotensin AT1 receptors improves cardinal symptoms of metabolic syndrome in diet-induced obesity in rats. Br J Pharmacol. 2014;171:746-60.