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从富含脂肪、果糖和胆固醇的饮食恢复到正常饮食,在哥廷根小型猪肥胖模型中可限制心肌胶原蛋白的含量。

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.

作者信息

Andreasen Laura Jul, Krog Simone, Ludvigsen Trine Pagh, Nielsen Ole Lerberg, Møller Jacob Eifer, Christoffersen Berit Østergaard, Pedersen Henrik Duelund, Olsen Lisbeth Høier

机构信息

1Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg, Denmark.

Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Måløv, Denmark.

出版信息

Nutr Metab (Lond). 2018 Sep 25;15:64. doi: 10.1186/s12986-018-0303-x. eCollection 2018.

Abstract

BACKGROUND

Dietary 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.

METHODS

Forty castrated male Göttingen Minipigs were assigned to three groups fed either standard minipig chow (SD,  = 8) for 13 months, fat/fructose/cholesterol-rich diet (FFC,  = 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,  = 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.

RESULTS

Myocardial collagen content quantified biochemically was significantly lower in FFC/SD compared to FFC ( = 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 (K) and plasma lipid levels.

CONCLUSION

Dietary 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.

摘要

背景

饮食干预已被证明可减轻一些与肥胖相关的心肌病理改变。本研究评估了从富含脂肪/果糖/胆固醇的饮食恢复到正常饮食对左心室(LV)心肌纤维化、脂肪浸润和肥大的影响,以及肥胖、血脂和糖代谢标志物对哥廷根小型猪肥胖模型心脏形态的具体影响。

方法

40只去势雄性哥廷根小型猪被分为三组,分别喂食标准小型猪饲料(SD,n = 8)13个月、富含脂肪/果糖/胆固醇的饮食(FFC,n = 16)13个月,或富含脂肪/果糖/胆固醇的饮食7个月,然后在剩余6个月改为标准小型猪饲料(FFC/SD,n = 16)。在6 - 7个月后(FFC/SD组饮食调整前)和处死前,对所有三组动物评估体重、体脂百分比、血脂和糖代谢标志物。此外,在处死时进行心肌胶原和甘油三酯含量的生化定量、纤维化和脂肪浸润的半定量组织学评估以及胶原和心肌细胞直径的定量组织学分析,并获取心脏重量。使用Kruskal - Wallis检验和Fisher精确检验对分类变量评估组间差异。进行Pearson相关分析以检验心肌变化与选定解释变量之间的相关性。对于非参数响应变量,应用Spearman相关分析。

结果

与FFC组相比,FFC/SD组生化定量的心肌胶原含量显著降低(P = 0.02)。此外,从富含脂肪/果糖/胆固醇的饮食恢复到正常饮食导致体重和体脂百分比停滞不前,静脉葡萄糖耐量指数(K)和血脂水平正常化。

结论

饮食恢复正常可使肥胖的哥廷根小型猪左心室胶原含量降低。尽管存在严重肥胖以及糖脂代谢显著恶化,但在该肥胖模型中仅发现轻度心肌变化,因此在进行饮食或药物干预之前,有必要进一步优化模型以诱导更严重的心肌变化。

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