Cardiac Dysfunction Induced by Obesity Is Not Related to β-Adrenergic System Impairment at the Receptor-Signalling Pathway

Abstract

Obesity has been shown to impair myocardial performance. Some factors have been suggested as responsible for possible cardiac abnormalities in models of obesity, among them beta-adrenergic (βA) system, an important mechanism of regulation of myocardial contraction and relaxation. The objective of present study was to evaluate the involvement of βA system components in myocardial dysfunction induced by obesity. Thirty-day-old male Wistar rats were distributed in control (C, n = 25) and obese (Ob, n = 25) groups. The C group was fed a standard diet and Ob group was fed four unsaturated high-fat diets for 15 weeks. Cardiac function was evaluated by isolated papillary muscle preparation and βA system evaluated by using cumulative concentrations of isoproterenol and Western blot. After 15 weeks, the Ob rats developed higher adiposity index than C rats and several comorbidities; however, were not associated with changes in systolic blood pressure. Obesity caused structural changes and the myocardial responsiveness to post-rest contraction stimulus and increased extracellular calcium (Ca2+) was compromised. There were no changes in cardiac function between groups after βA stimulation. The obesity was not accompanied by changes in protein expression of G protein subunit alpha (Gsα) and βA receptors (β1AR and β2AR). In conclusion, the myocardial dysfunction caused by unsaturated high-fat diet-induced obesity, after 15 weeks, is not related to βAR system impairment at the receptor-signalling pathway.

Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β -adrenergic system and does not compromise cardiac function

“…; Ferron et al. ), and oppose to Carroll et al. (), who observed decreased responsiveness to isoproterenol in obese rabbits fed with UHFD for 12 weeks.…”

Early Weight Loss Independent Effects of Sleeve Gastrectomy on Diet-Induced Cardiac Dysfunction in Obese, Wistar Rats

“…We have found the Wistar rat to be obesity-prone, and multiple authors have published the Wistar rat to be a susceptible rodent strain to cardiac dysfunction of a HFD [19–22]. Samniang et al found 12 weeks of a HFD fed to male Wistar rats induced significantly increased body weight, plasma insulin, HOMA index, total cholesterol, and LDL levels as well as significant reductions in FS% and systolic blood pressure.…”

“…A HFD also induced cardiac autonomic imbalance, cardiac myocardial dysfunction, and increased circulating and cardiac tissue oxidative stress [21]. Many of these metabolic derangements are shared with patients who are morbidly obese with cardiac metabolic disease including hypertriglyceridemia, hypertension, glucose intolerance, and hyperleptinemia [22]. However, the relationship between obesity and heart failure development in humans is complex involving multiple different pathways that ultimately affect cardiac function.…”

Cardiac β‐adrenergic responsiveness of obese Zucker rats: The role of AMPK

“…Our observation of reduced β‐adrenergic responsiveness in hearts of obese rats confirms previous findings, not only in isolated rat and rabbit hearts (Carroll et al., ; Carroll, Kyser, & Martin, ; Jiang et al., ; Lima‐Leopoldo et al., ), but also using cardiac membranes (Bass & Ritter, ; Chatelain et al., ; Strassheim et al., ), and more importantly, in vivo assessment in conscious conditions (Bunag et al., ; Bussey et al., ). In some studies, it was not possible to associate the reduced β‐adrenergic responsiveness of the obese heart with a downregulation of the β‐ARs (Carroll et al., ; Ernsberger, Koletsky, Baskin, & Foley, ; Ferron et al., ; Hohl et al., ; Minhas et al., ; Vileigas et al., ), potentially owing to differences in obese animal models and technical approaches. However, in several other studies, using obese Zucker rats, downregulation of β‐ARs was observed (Chatelain et al., ; Jiang et al., ; Strassheim et al., ), as found in our study.…”

“…This, however, does not exclude the possibility that other β‐AR subtypes could be affected during obesity (Chatelain et al., ; Jiang et al., ; Strassheim et al., ) or play an important supportive role in the pathophysiology of obesity and diabetes (Cook et al., ; Li et al., ; Perez‐Schindler et al., ). More importantly, given that from a clinical viewpoint targeting β‐ARs with β‐blockers is commonly advised against in obese individuals owing to their unfavourable metabolic effects (Gress et al., ; Sharma et al., ) and given that β‐AR downregulation is most probably not the sole mechanism underlying the reduced β‐adrenergic responsiveness of the heart in obesity (Ferron et al., ; Vileigas et al., ), alternative mechanisms should be explored.…”