Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca²⁺Handling

Abstract

BackgroundDiet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that.ObjectiveTo evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling.MethodsThirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers.ResultsThe high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats.ConclusionObesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling.

Cardiac Remodeling in Obesity-Resistance Model is not Related to Collagen I and III Protein Expression

“…However, some individuals remain resistant to becoming obese, a condition also observed in some animals' fed with high-fat diets, which are defined as obesity-resistant animals. [8][9][10]24,25 Within this context, some authors have reported that around 40% of the animals fed with a high-fat diet are classified as ROb. [8][9][10]23 Some possible pathways to explain the obesity resistance include: increased expression of some thermogenic enzymes and decreased expression of lipogenic enzymes in adipose tissues of ROb rats, as well as the suppression of lipogenesis and the acceleration of fatty-acid oxidation in visceral fat.…”

“…11 However, no studies have evaluated the contribution of collagen expression to cardiac remodeling in obesity-resistant animal models, and the few studies that evaluated the cardiac changes in this condition found divergent results. Sá et al 9 found isolated papillary muscle contraction impairment, while Carroll et al 10 found cardiac no abnormalities in obesity-resistant animals fed with a high-fat diet.…”

“…The sample size and the experimental period were based on previous studies conducted by our research group. 9,11,12 Animals were kept in individual cages with controlled temperature (24 ± 2 ºC), humidity (55 ± 5%), and light (12-h light/dark cycle). The diet and water were ad libitum.…”

“…The diet and water were ad libitum. The experimental procedures were performed according to the "Guide for the Care and Use of Laboratory Animals" 9,13 and approved by the Animal Ethics Committee of the Botucatu Medical School (991/2012). At the end of the experimental protocol, after 8h fasting, the animals were euthanized by decapitation after intraperitoneal anesthesia with a mixture of ketamine (1 mg/kg) and xylazine (100 mg/kg) (Syntec, Rhobifarma Indústria Farmacêutica Ltda., Hortolândia, São Paulo, Brazil).…”

“…Within this context, experiments using animals fed with a high-fat diet try to understand the pathophysiological susceptibility of obesity-resistant individuals to cardiometabolic diseases. [8][9][10]…”