Animal models of obesity/diabetes: Influence of the angiotensin system on neurovascular coupling and memory formation

Project Description:

Chronic therapy with AT1 receptor blockers (ARBs, which are clinically established for treating high blood pressure) are experimental demonstrated to prevent obesity without exactly knowing the underlying mechanisms. We recently had shown that brain- and Ang(1-7)-dependent pathways are involved and that leptin function is improved. We here mainly want to investigate whether improved leptin function after ARB treatment is related to a better cerebral blood flow and whether brain glucose uptake is affected by ARB treatment.


Experimental Methods:

  • Working with genetically modified mice (Mas ko mice, db/db mice, ob/ob mice)
  • Chronic treatment of mice with ARB
  • Phenotyping of mice including measurement of blood pressure, food intake, locomotion, energy expenditure (indirect calorimetry), glucose control (insulin tolerance test), fat mass (MRT)
  • Cerebral blood flow by laser speckle imaging
  • Cerebral glucose uptake by PET scanning (provided that PET is available)
  • DNA and RNA extraction, PCR, qPCR
  • Biochemical multiplex analysis of adipokines and various endocrine parameters

Publications

Schuster, F., Huber, G., Stölting, I., Wing, E. E., Saar, K., Hübner, N., Banks, W. A., and Raasch, W.: Telmisartan prevents diet-induced obesity and preserves leptin transport across the blood-brain barrier in high-fat diet-fed mice. Pflugers Arch, vol. [Epub ahead of print], , 2018, doi: 10.1007/s00424-018-2178-0

Huber, G., Schuster, F., and Raasch, W.: Brain renin-angiotensin system in the pathophysiology of cardiovascular diseases. Pharmacol Res., vol. pii: S1043-6618(17), pp. 30514-5, 2017, doi: 10.1016/j.phrs.2017.06.016