Influence of bariatric surgery on cardiac beta-adrenergic signalling
MD student: Pia Schlinkert Supervisor at TUD: Ali El-Armouche Supervisor at KCL: Francesco Rubino Start date: 01.10.2017 Date of defense: 26.05.2021 Dr. med. |
Obesity and diabetes are turning into global health issues. A promising therapeutic option for the treatment of severe obesity is bariatric surgery. Bariatric interventions lead to an improved heart function and help to reduce the cardiovascular risk. The molecular links between bariatric interventions and the heart are not yet understood. Material and methods. To investigate the effects of obesity and bariatric interventions upon the heart we used a high fat diet mouse model and a high fat diet rat model with bariatric intervention (duodenojejunal bypass, DJB). Left ventricular tissue of those models was analysed using qPCR and Western Blot. RNA sequencing of the rat heart tissue was performed.
The HFD did not result in alterations in the contractility parameters analysed by echocardiography of the mouse hearts. The high fat feeding led to alterations in the glucose metabolism, the HFD mice showed a different reaction to glucose and insulin injections. The analysis of left ventricular tissue showed a down-regulation of Glut1 and Glut4. In the left ventricular tissue of the rats we observed an upregulation of Glut1 expression in the DJB group. Protein expression was not altered. The expression of representative genes in the fatty acid oxidation was not affected by DJB. The RNA sequencing showed alterations in the adrenergic signalling pathway and the oxidative phosphorylation.
Obesity and a prediabetic metabolism lead to down-regulation of Glut1 and Glut4 in the left ventricle. The bariatric intervention DJB promoted an upregulation of cardiac Glut1 expression. The molecular analysis of representative genes involved in the adrenergic signalling cascade did not show any alterations but RNA sequencing analysis showed significant changes in other genes involved in this pathway. The protective effects of Glut1 upregulation and the possible role of oxidative phosphorylation seem like promising targets for future experiments.
Publications:
Estrogen determines sex differences in adrenergic vessel tone by regulation of endothelial beta-adrenoceptor expression. K. Riedel, A.J. Deussen, J. Tolkmitt, S. Weber, P. Schlinkert, B. Zatschler, C. Friebel, B. Muller, A. El-Armouche, H. Morawietz, K. Matschke, I. Kopaliani. Am J Physiol Heart Circ Physiol. 2019;317:H243-H254.
Insulin and obesity transform hypothalamic-pituitary-adrenal axis stemness and function in a hyperactive state. M. Werdermann, I. Berger, L.D. Scriba, A. Santambrogio, P. Schlinkert, H. Brendel, H. Morawietz, A. Schedl, M. Peitzsch, A.J.F. King, C.L. Andoniadou, S.R. Bornstein, C. Steenblock. Mol Metab. 2021;43:101112.