Abstract
BackgroundDietary interventions have been shown to attenuate some of the myocardial pathological alterations associated with obesity. This study evaluated the effect of dietary normalization from a fat/fructose/cholesterol-rich diet to chow on left ventricular (LV) myocardial fibrosis, fat infiltration and hypertrophy but also the specific influence of obesity, plasma lipids and glucose metabolism markers on heart morphology in a Göttingen Minipig model of obesity.MethodsForty castrated male Göttingen Minipigs were assigned to three groups fed either standard minipig chow (SD, n = 8) for 13 months, fat/fructose/cholesterol-rich diet (FFC, n = 16) for 13 months or fat/fructose/cholesterol-rich diet for 7 months and then changed to standard minipig chow for the remaining 6 months (FFC/SD, n = 16). Body weight, body fat percentage, plasma lipids and glucose metabolism markers were evaluated in all three groups after 6–7 months (prior to diet adjustment for FFC/SD) and again before termination. Further, biochemical quantification of myocardial collagen and triglyceride content, semi-quantitative histological evaluation of fibrosis and fat infiltration and quantitative histological analysis of collagen and cardiomyocyte diameter were performed and heart weight was obtained after termination. Group differences were evaluated using Kruskal-Wallis test and Fisher’s exact test for categorical variables. Pearson correlation analysis was performed to test for correlations between myocardial changes and selected explanatory variables. For non-parametric response variables, a Spearman correlation analysis was applied.ResultsMyocardial collagen content quantified biochemically was significantly lower in FFC/SD compared to FFC (P = 0.02). Furthermore, dietary normalization from a fat/fructose/cholesterol-rich diet to chow caused stagnation of body weight and body fat percentage, normalized intravenous glucose tolerance index (KG) and plasma lipid levels.ConclusionDietary normalization led to lower LV collagen content in obese Göttingen Minipigs. Despite gross obesity and significant deteriorations in glucose and lipid metabolism, only mild myocardial changes were found in this model of obesity and therefore further model optimization is warranted in order to induce more severe myocardial changes before dietary or pharmacological interventions.
Highlights
Dietary interventions have been shown to attenuate some of the myocardial pathological alterations associated with obesity
Body fat percentage and lean body mass (LBM) were significantly higher in Obese animals fed fat/fructose/cholesterol-rich diet (FFC) and FFC/Lean control animals fed standard minipig chow (SD) compared to SD animals mid-study
SD fed standard chow, FFC fed fat/fructose/cholesterol-rich diet, FFC/SD dietary normalization, BW body weight, LBM lean body mass, HW heart weight **P < 0.01; ***P < 0.001, significantly different from SD, †††P < 0.001; ††††P < 0.0001, significantly different from FFC a n = 13 study termination BW and body fat percentage were significantly higher in FFC and FFC/SD compared to SD animals, and these body composition measurements were significantly lower in FFC/SD compared to FFC
Summary
Dietary interventions have been shown to attenuate some of the myocardial pathological alterations associated with obesity. Obesity is associated with myocardial accumulation of intra-myocellular lipids causing lipoapoptosis [5,6,7], left ventricular (LV) hypertrophy [8, 9], and to some degree increased myocardial fibrosis [10, 11]. These obesity-induced myocardial alterations may contribute to impairment of LV function [7, 12,13,14,15] and HF. Translational animal models mimicking human obesity could facilitate more effective research in this field, enabling investigations of the underlying mechanisms and providing a better understanding of the related co-morbidities
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