A High-Fat Diet Induces Cardiac Damage in Obesity-Resistant Rodents with Reduction in Metabolic Health

Abstract

Background/aims: Obesity resistance is associated with the complex interaction of stringent and environmental factors that confer the ability to resist mass gain and body fat deposition, even when eating high-calorie diets. Considering that there are numerous gaps in the literature on the metabolic processes that explain Obesity resistance, specifically in relation to oxidative stress, the purpose of the study was to investigate whether obesity-resistant (OR) rats develop elevated reactive oxygen species in cardiac tissue.

Methods: Wistar rats were initially randomized into two groups: a standard diet (SD) and a high-fat diet (HFD) group. The SD and HFD groups were further divided into control (C), OR, and obese prone (OP) subgroups based on body weight. This criterion consisted of organizing the animals in each group in ascending order according to body weight (BW), and the cutoff point was identified in the animals by terciles: 1) lower BW; 2) intermediate BW; and 3) higher BW. Rats were sacrificed on the 14th week, and serum and organs were collected. Nutritional assessment, food profiles, histological analysis, comorbidities, and cardiovascular characteristics were determined.

Results: BW showed a significant difference between the standard diet and high-fat diet groups in the 4th week of the experimental protocol, characterizing obesity. In the 4th week, after the characterization of Obesity resistance, there was a significant difference in BW between groups C, OP, and OR. The OP and OR groups showed a significant increase in caloric intake in relation to the C group. The OP group showed a significant increase in final BW, retroperitoneal fat pad mass, sum of corporal fat deposits and reactive oxygen species, in relation to groups C and OR. The area under the glycemic curve, insulin resistance index and basal glucose were elevated in the OP group in relation to the C. OP also promoted an increase in HOMA-IR when compared with C. OR rats showed a non-significant increase in insulin and HOMA-IR in OR vs. C (p = ~0.1), but no significant differences were observed between OP vs. OR for these parameters, suggesting that both groups suffered from decreased metabolic health. Total cardiac mass, left ventricular cross-sectional area, and cholesterol levels were significantly elevated in the OP and OR groups compared with the C group.

Conclusion: A high-fat diet induces cardiac damage in obesity-resistant rodents with reduction in metabolic health.

Keywords: Oxidative stress; Obesity Resistance; Hypercaloric diets; Cardiac; Heart.