Department of Nutrition, Gillings School of Global Public Health, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
PLoS One. 2012;7(6):e38812. doi: 10.1371/journal.pone.0038812. Epub 2012 Jun 12.
Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to "Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic Syndrome.
肥胖已在全球范围内达到流行程度。存在几种肥胖动物模型，但缺乏将传统的猪油基高脂肪饮食（HFD）与由营养不佳的人类垃圾食品组成的“自助餐厅饮食”（CAF）进行比较的研究。我们之前的工作表明，与 HFD 相比，CAF 具有快速而严重的致肥胖和炎症后果，包括体重迅速增加、代谢综合征标志物、多组织脂质积累以及剧烈的炎症。为了确定 CAF 诱导肥胖和代谢综合征的潜在介质，我们使用代谢组学分析来分析喂食 CAF、HFD 或标准对照饮食的大鼠的血清、肌肉和白色脂肪。主成分分析确定了脂肪酸和酰基辅酶 A 簇的升高。这些代谢物的增加与全身线粒体功能障碍有关，与 CAF 喂养大鼠的体重增加、代谢综合征的生理测量以及组织炎症平行。代谢物、生理和组织学发现之间的斯皮尔曼成对相关性表明，CAF 喂养动物中升高的炎症标志物之间存在很强的相关性，这些标志物表现为脂肪中的冠状结构，特别是促炎饱和脂肪酸和氧化中间产物月桂酸和月桂酰肉碱。用肉碱处理骨髓来源的巨噬细胞可通过下调 AMPK 和分泌促炎细胞因子使巨噬细胞向 M1 促炎表型极化。本文介绍的结果表明，与传统的 HFD 模型相比，CAF 饮食为饮食诱导的人类肥胖提供了一个强大的模型，该模型模拟了与代谢综合征相关的线粒体功能障碍在血清、肌肉和脂肪中的变化，以及促炎代谢物的改变。这些数据还表明，改变饱和脂肪酸的可用性或代谢可能会限制与肥胖相关的炎症，从而导致代谢综合征。
