Dietary normalization from a fat, fructose and cholesterol-rich diet to chow limits the amount of myocardial collagen in a Göttingen Minipig model of obesity

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.

Experimental non-alcoholic steatohepatitis in Göttingen Minipigs: consequences of high fat-fructose-cholesterol diet and diabetes

“…Results are presented as median and 25% and 75% quartiles. Results for BW, BF%, TC, TG, KG and AUC Insulin in diet group SD, FFC and FFC/SD have been presented previously [17] ALB albumin, ALP alkaline phosphatase, ALT alanine transaminase, AST aspartate transaminase, AUC Insulin area under the curve of insulin, BF% total body fat percentage, BW body weight, CRP C-reactive protein, FRA fructosamine, GLDH glutamate dehydrogenase, GLU glucose, FFC high fat/fructose/cholesterol diet group, FFC DIA diabetic group, FFC/SD diet-normalization group, HOMA-IR homeostasis model assessment of insulin resistance, K G intravenous glucose tolerance index, LW liver weight, LW:BW liver weight:body weight, NA not applicable, SD lean control group, TC total cholesterol, TG triglycerides ^ Transformed a Significantly different from SD b Significantly different from FFC 1 n = 6 for SD, n = 13 for FFC, n = 12 for FFC/SD, n = 6 for FFC DIA , due to catheter failure 2 n = 6 for SD, n = 13 for FFC, n = 9 for FFC/SD, n = 6 for FFC DIA 3 n = 5 for SD, n = 13 for FFC, n = 8 for FFC/SD, n = 4 for FFC DIA 4 n = 6 for SD, n = 14 for FFC, n = 10 for FFC/SD…”

“…Results are presented as median and 25% and 75% quartiles. Results for BW, BF%, TC, TG, KG and AUC Insulin in diet group SD, FFC and FFC/SD have been presented previously [17]…”

“…1a) and fed once daily for 13 months. The pigs were part of a larger study (n = 84 in total) looking at different aspects of obesity [17] and diabetes related complications (two intervention groups were not included in the present study). The included groups were: lean control pigs (SD, n = 8) fed standard diet (Mini-pig, SDS, UK (Table 1)); a group fed high fat/fructose/cholesterol (2%) diet (5B4L) for the first 5 months and subsequently changed to a similar diet with 1% cholesterol (9G4U) for the next 8 months [both diets from Test diet ® , Missouri, USA (Table 1)] (high fat/fructose/cholesterol, FFC, n = 16); a group fed the same diets as FFC for the first 7 months but returned to standard diet the last 6 months of the study (diet-normalization, FFC/SD, n = 16) and a diabetic group fed a high fat/fructose/cholesterol (1%) diet throughout the study (9G4U) (FFC DIA , n = 14).…”

“…After centrifugation EDTA plasma and serum were pipetted into appropriate tubes and stored at − 80 °C. The IVGTT procedure including calculation of intravenous glucose tolerance index (K G ) and area under the curve for insulin response (AUC Insulin ) were performed as previously described [17]. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as fasting insulin (µU/mL) × fasting glucose (mM)/22.5 [19] in all animals except for the diabetic animals since their fasting glucose values were also influenced by the long-acting insulin glargine.…”

The expression signatures in liver and adipose tissue from obese Göttingen Minipigs reveal a predisposition for healthy fat accumulation

“…The included groups were: a lean control pigs (SD, N = 7) fed standard diet (Mini-pig, SDS, UK); a group fed high fat/fructose/cholesterol diet (FFC, N = 14) with (2%) cholesterol (5B4L) for the first five months and changed to a similar diet with 1% cholesterol (9G4U) for the next eight months (Test diet®, Missouri, USA); a streptozotocin-induced diabetic group (FFC DIA , N = 8) fed a high fat/fructose/cholesterol (1%) diet throughout the study (9G4U). Data from the same 29 pigs have been included in parallel studies focusing on histological changes in the liver tissue and myocardial changes 12,15 . Basic phenotypic and metabolic characteristics, measured as described in 12 are reported in Table 1.…”