Effects of Obesity and Diabesity on Ventricular Muscle Structure and Function in the Zucker Rat

Abstract

(1) Background: Cardiovascular complications are a leading cause of morbidity and mortality in diabetic patients. The effects of obesity and diabesity on the function and structure of ventricular myocytes in the Zucker fatty (ZF) rat and the Zucker diabetic fatty (ZDF) rat compared to Zucker lean (ZL) control rats have been investigated. (2) Methods: Shortening and intracellular Ca2+ were simultaneously measured with cell imaging and fluorescence photometry, respectively. Ventricular muscle protein expression and structure were investigated with Western blot and electron microscopy, respectively. (3) Results: The amplitude of shortening was increased in ZF compared to ZL but not compared to ZDF myocytes. Resting Ca2+ was increased in ZDF compared to ZL myocytes. Time to half decay of the Ca2+ transient was prolonged in ZDF compared to ZL and was reduced in ZF compared to ZL myocytes. Changes in expression of proteins associated with cardiac muscle contraction are presented. Structurally, there were reductions in sarcomere length in ZDF and ZF compared to ZL and reductions in mitochondria count in ZF compared to ZDF and ZL myocytes. (4) Conclusions: Alterations in ventricular muscle proteins and structure may partly underlie the defects observed in Ca2+ signaling in ZDF and ZF compared to ZL rat hearts.

Regulation of Prepro-NeuropeptideW/B and Its Receptor in the Heart of ZDF Rats: An Animal Model of Type II DM

“…The calcium transient amplitude was decreased in the cardiomyocytes from diabetic animals, similar to other animal models, db/db type 2 diabetic mice [ 28 ], and streptozotocin-induced type 1 diabetic rats [ 29 ]. The calcium transient reduction was not observed in studies on type 2 diabetic ZDF rats [ 30 , 31 ] which were performed on 10 and 14 weeks, i.e., younger animals than in the presented study, however. The diminished calcium transient did not cause a significant change in the amplitude of sarcomeric contraction in diabetic cardiomyocytes which followed previous findings in ZDF rats [ 30 , 31 ].…”

“…The calcium transient reduction was not observed in studies on type 2 diabetic ZDF rats [ 30 , 31 ] which were performed on 10 and 14 weeks, i.e., younger animals than in the presented study, however. The diminished calcium transient did not cause a significant change in the amplitude of sarcomeric contraction in diabetic cardiomyocytes which followed previous findings in ZDF rats [ 30 , 31 ]. A possible explanation could be provided by an increased myofilament calcium sensitivity serving as a compensatory mechanism in ZDF rats [ 32 ].…”