Depletion of the gut microbiota differentially affects the impact of whey protein on high-fat diet-induced obesity and intestinal permeability.
Depletion of the gut microbiota differentially affects the impact of whey protein on high-fat diet-induced obesity and intestinal permeability.
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DOI：
10.14814/phy2.14867
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发表时间：
2021-06
影响因子：
2.5
通讯作者：
Nilaweera KN
中科院分区：
文献类型：
--
作者：
Boscaini S;Cabrera-Rubio R;Golubeva A;Nychyk O;Fülling C;Speakman JR;Cotter PD;Cryan JF;Nilaweera KN
乳清蛋白分离物（WPI）被认为是肥胖的饮食解决方案。然而，WPI作用的确切机制仍然知之甚少，但可能与其对能量平衡，肥胖和代谢的有益作用有关。最近，它调节肠道微生物群的能力受到越来越多的关注。在这里，我们使用抗生素鸡尾酒（ABX）管理的微生物群消耗，以研究肠道微生物群是否介导高脂饮食（HFD）-WPI消耗期间观察到的生理和代谢变化。C57 BL/6 J小鼠接受含HFD的WPI（HFD-WPI）或对照非乳清乳蛋白酪蛋白（HFD-CAS）5或10周。在5周或10周的ABX治疗干预后，相对于HFD-CAS-喂养小鼠，补充WPI的HFD-喂养小鼠显示体重增加、肥胖、皮下脂肪组织（eWAT）中的Ob基因表达水平和血浆瘦素降低。在10周的干预后，ABX和WPI在降低肥胖和瘦素可用性方面具有累加效应。与喂食HFD-CAS的小鼠相比，喂食HFD-WPI的小鼠显示回肠和eWAT内编码促炎标志物（MCP-1、TNFα和CD 68）的基因表达降低，但在微生物群耗竭后未显示变化。此外，WPI补充降低了HFD诱导的回肠远端肠通透性破坏;这种作用可通过长期ABX治疗逆转。总之，WPI主要通过非微生物群依赖性机制逆转HFD对代谢和生理功能的影响。此外，我们证明了WPI对HFD诱导的炎症和回肠通透性破坏的保护作用，后者被肠道微生物群消耗逆转。在这项研究中，我们对乳清蛋白消费的抗肥胖作用提供了新的见解。在这种情况下，我们通过使用基于抗生素治疗的消耗方法研究了肠道微生物群的作用。此外，我们还发现了含有乳清蛋白的高脂肪饮食对炎症、肠道通透性和代谢产物谱的影响。
Whey protein isolate (WPI) is considered a dietary solution to obesity. However, the exact mechanism of WPI action is still poorly understood but is probably connected to its beneficial effect on energy balance, adiposity, and metabolism. More recently its ability to modulate the gut microbiota has received increasing attention. Here, we used a microbiota depletion, by antibiotic cocktail (ABX) administration, to investigate if the gut microbiota mediates the physiological and metabolic changes observed during high‐fat diet (HFD)‐WPI consumption. C57BL/6J mice received a HFD containing WPI (HFD‐WPI) or the control non‐whey milk protein casein (HFD‐CAS) for 5 or 10 weeks. HFD‐fed mice supplemented with WPI showed reduced body weight gain, adiposity, Ob gene expression level in the epidydimal adipose tissue (eWAT) and plasma leptin relative to HFD‐CAS‐fed mice, after 5‐ or 10‐weeks intervention both with or without ABX treatment. Following 10‐weeks intervention, ABX and WPI had an additive effect in lowering adiposity and leptin availability. HFD‐WPI‐fed mice showed a decrease in the expression of genes encoding pro‐inflammatory markers (MCP‐1, TNFα and CD68) within the ileum and eWAT, compared to HFD‐CAS‐fed mice, without showing alterations following microbiota depletion. Additionally, WPI supplementation decreased HFD‐induced intestinal permeability disruption in the distal ileum; an effect that was reversed by chronic ABX treatment. In summary, WPI reverses the effects of HFD on metabolic and physiological functions through mainly microbiota‐independent mechanisms. Moreover, we demonstrate a protective effect of WPI on HFD‐induced inflammation and ileal permeability disruption, with the latter being reversed by gut microbiota depletion. In this study, we provided new insights on the anti‐obesity effect of whey protein consumption. In this instance, we investigated the role of the gut microbiota by using an antibiotic treatment‐based depletion approach. Moreover, we showed novel findings on the effect of a high‐fat diet containing whey protein on inflammation, intestinal permeability and metabolites profile.