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

Abstract

Obesity is a worldwide pandemic associated with high incidence of cardiovascular disease. The mechanisms by which the obesity leads cardiac dysfunction are not fully elucidated and few studies have evaluated the relationship between obesity and proteins involved in myocardial β‐adrenergic (βA) system. The purpose of this study was to evaluate the cardiac function and βA pathway components in myocardium of obese rats. Male Wistar rats were distributed into two groups: control (n = 17; standard diet) and obese (n = 17; saturated high‐fat diet) fed for 33 weeks. Nutritional profile and comorbidities were assessed. Cardiac structure and function was evaluated by macroscopic postmortem, echocardiographic and isolated papillary muscle analyzes. Myocardial protein expression of β 1‐ and β 2‐adrenergic receptors, Gαs protein, adenylate cyclase (AC) and protein kinase A (PKA) was performed by Western blot. Cardiac cyclic adenosine monophosphate (cAMP) levels and PKA activity were assessed by ELISA. Obese rats showed increased adiposity index (P < 0.001) and several comorbidities as hypertension, glucose intolerance, insulin resistance, and dyslipidemia compared with control rats. Echocardiographic assessment revealed increased left atrium diameter (C: 4.98 ± 0.38 vs. Ob: 5.47 ± 0.53, P = 0.024) and posterior wall shortening velocity (C: 37.1 ± 3.6 vs. Ob: 41.8 ± 3.8, P = 0.007) in obese group. Papillary muscle evaluation indicated that baseline data and myocardial responsiveness to isoproterenol stimulation were similar between the groups. Protein expression of myocardial AC was higher in obese group than in the control (C: 1.00 ± 0.21 vs. Ob: 1.25 ± 0.10, P = 0.025), whereas the other components were unchanged. These results suggest that saturated high‐fat diet‐induced obesity was not effective in triggering cardiac dysfunction and impair the beta‐adrenergic signaling.

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.…”

“…given that from a clinical viewpoint targeting -ARs with -blockers is commonly advised against in obese individuals owing to their unfavourable metabolic effects (Gress et al, 2000;Sharma et al, 2001) and given that -AR downregulation is most probably not the sole mechanism underlying the reduced -adrenergic responsiveness of the heart in obesity (Ferron et al, 2015;Vileigas et al, 2016), alternative mechanisms should be explored.…”

The influence of obesity by a diet high in saturated fats and carbohydrates balance in the manifestation of systemic complications and comorbidities

“…However, in this study, this type of carbohydrate was not used, since this would not allow knowing if the manifestation of the complications and comorbidities would be exclusively due to the increase of the amount of fat or its association with a carbohydrate with harmful capacity. It is believed that other factors may also have influenced this result as time of exposure to diet, fat percentage, and type (saturated or unsaturated) and source (animal or vegetable) of fatty acids and animal model [6,17,18,30,33,[35][36][37].…”

A Redução do Colágeno Tipo I está Associada ao Aumento da Atividade da Metaloproteinase-2 e da Expressão Proteica de Leptina no Miocárdio de Ratos Obesos

“…The sample size used in this study was based on the literature and on our previous studies. 13,[17][18][19] The control group was fed standard rat chow (RC Focus 1765, Agroceres ® , Rio Claro, SP, Brazil) containing 12.3% of kilocalories from fat, 57.9% from carbohydrates, and 29.8% from protein, whereas the obese group was fed one of four alternating high-fat diets (RC Focus 2413, 2414, 2415, and 2416, Agroceres ® , Rio Claro, SP, Brazil) containing 49.2% of kilocalories from fat, 28.9% from carbohydrates, and 21.9% from protein. The four high-fat diets had the same nutritional composition, except flavoring additives, namely, cheese, bacon, chocolate, or vanilla.…”