van der Heijden Roel A, Morrison Martine C, Sheedfar Fareeba, Mulder Petra, Schreurs Marijke, Hommelberg Pascal P H, Hofker Marten H, Schalkwijk Casper, Kleemann Robert, Tietge Uwe J F, Koonen Debby P Y, Heeringa Peter
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands; Top Institute Food and Nutrition, 6709 AN Wageningen, Netherlands.
Top Institute Food and Nutrition, 6709 AN Wageningen, Netherlands; Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, Netherlands.
Mediators Inflamm. 2016;2016:2042107. doi: 10.1155/2016/2042107. Epub 2016 Jun 6.
Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential. Methods. Male C57BL/6J mice (n = 52) received a control low-fat diet (LFD; 10 kcal% fat) for 6 weeks followed by 24 weeks of either LFD (n = 13) or high-fat diet (HFD; 45 kcal% fat; n = 13) or HFD supplemented with 0.1% w/w of the flavanol compound epicatechin (HFD+E; n = 13) or an anthocyanin-rich bilberry extract (HFD+B; n = 13). Energy substrate utilization was determined by indirect calorimetry in a subset of mice following the dietary switch and at the end of the experiment. Blood samples were collected at baseline and at 3 days and 4, 12, and 20 weeks after dietary switch and analyzed for systemic lipids and proinflammatory cytokines. Adipose tissue (AT) histopathology and inflammatory gene expression as well as hepatic lipid content were analyzed after sacrifice. Results. The switch from a LFD to a HFD lowered the respiratory exchange ratio and increased plasma cholesterol and hepatic lipid content. These changes were not attenuated by HFD+E or HFD+B. Furthermore, the polyphenol compounds could not prevent HFD-induced systemic rise of TNF-α levels. Interestingly, a significant reduction in Tnf gene expression in HFD+B mice was observed in the AT. Furthermore, HFD+B, but not HFD+E, significantly prevented the early upregulation of circulating neutrophil chemoattractant mKC. However, no differences in AT histopathology were observed between the HFD types. Conclusion. Supplementation of HFD with an anthocyanin-rich bilberry extract but not with the flavanol epicatechin may exert beneficial effects on the systemic early inflammatory response associated with diet-induced obesity. These systemic effects were transient and not observed after prolongation of HFD-feeding (24 weeks). On the tissue level, long-term treatment with bilberry attenuated TNF-α expression in adipose tissue.
背景。来自黄烷醇和花青素家族的天然多酚类物质已被认为在肥胖过程中发挥有益作用。我们推测它们对减轻肥胖诱导的血脂异常以及相关炎症后遗症的作用尤其具有促进健康的潜力。方法。雄性C57BL/6J小鼠(n = 52)先接受6周的对照低脂饮食(LFD;10千卡%脂肪),随后24周分别给予LFD(n = 13)、高脂饮食(HFD;45千卡%脂肪;n = 13)、补充0.1% w/w黄烷醇化合物表儿茶素的HFD(HFD+E;n = 13)或富含花青素的越橘提取物的HFD(HFD+B;n = 13)。在饮食转换后及实验结束时,通过间接量热法在一部分小鼠中测定能量底物利用情况。在基线以及饮食转换后3天、4周、12周和20周采集血样,分析全身血脂和促炎细胞因子。处死小鼠后分析脂肪组织(AT)组织病理学、炎症基因表达以及肝脏脂质含量。结果。从LFD转换为HFD降低了呼吸交换率,增加了血浆胆固醇和肝脏脂质含量。这些变化未被HFD+E或HFD+B减弱。此外,多酚化合物无法阻止HFD诱导的TNF-α水平全身性升高。有趣的是,在HFD+B小鼠的AT中观察到Tnf基因表达显著降低。此外,HFD+B而非HFD+E显著阻止了循环中性粒细胞趋化因子mKC的早期上调。然而,不同HFD类型之间在AT组织病理学上未观察到差异。结论。用富含花青素的越橘提取物而非黄烷醇表儿茶素补充HFD可能对与饮食诱导肥胖相关的全身早期炎症反应产生有益影响。这些全身效应是短暂的,在延长HFD喂养(24周)后未观察到。在组织水平上,长期用越橘治疗可减弱脂肪组织中TNF-α的表达。
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