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

Artur Junio Togneri Ferron,Bruno Barcellos Jacobsen,Dijon Henrique Salomé De Campos,Loreta Casquel De Tomasi,Paula Grippa Sant’Ana,Ana Paula Lima-Leopoldo,André Soares Leopoldo,Antonio Carlos Cicogna,Renata De Azevedo Mello Luvizotto,Xiongwen Chen

doi:10.1371/journal.pone.0138605

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.

Highlights

Obesity is a complex disease characterised by excessive accumulation of adipose tissue that affects 30% of the world population and 10.5 million Brazilians [1,2]
From the exclusion criteria mentioned in the characterisation of the groups, twenty rats remained in the study in the C group (C, n = 20) and seventeen remained in the obese group (Ob, n = 17)
Despite the greater amount of energy from high-fat diets, the calorie intake was similar between the groups due to the reduced food consumption (FC) in the Ob rats compared to the C rats (Fig 2A and 2B)

Summary

Introduction

Obesity is a complex disease characterised by excessive accumulation of adipose tissue that affects 30% of the world population and 10.5 million Brazilians [1,2]. Clinical research shows that excess fat causes cardiac abnormalities such as haemodynamic, morphologic and functional changes that correlate with the duration and intensity of obesity [5,6]. Within this context, experimental obesity using genetic models [7,8] or dietary manipulations [9,10,11,12] has become an important alternative for the study of obesity and cardiac function. Several studies have shown that obesity induced by different types of high-fat diets and/or highly energetic diets promotes myocardial dysfunction in rodents [10,13,14]. Recent researches performed in our laboratory show that obese rats fed a high-fat diet for 15 weeks presented myocardial dysfunction at the baseline condition and after inotropic manoeuvres [14,16]

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Results

Conclusion