Nature子刊:延长母乳喂养时间,可预防成年后肥胖

2022-07-28 生物世界 生物世界

该研究发现,延长母乳喂养时间,能够避免长大后由饮食引起的肥胖,这种现象可能是因为肝脏分泌的FGF21蛋白对下丘脑的作用,下丘脑在调控机体能量消耗与利用方面起到了关键作用。

母乳是婴儿最理想的天然食物,不仅安全,而且容易消化吸收,有利于促进肠道健康发育。

由于母乳含有新生儿出生后6个月内所需的所有营养素,世界卫生组织的母乳喂养指南建议,在婴儿半岁前应得到纯母乳喂养,以实现生长发育的最佳健康水平;而且即使6个月以后的母乳,也仍然是婴儿能量和高质量营养素的重要来源。

已有大量研究表明,母乳喂养无论是对母体还是对婴儿都具有多种健康益处,包括降低母亲患乳腺癌卵巢癌骨质疏松,以及肥胖的风险;对于婴儿来说,母乳喂养可以增加免疫力,预防多种疾病,同时,也包括降低日后肥胖的风险。

众所周知,肥胖是一种多因素病理,受环境、遗传和表观遗传因素的影响。总的来说,肥胖是由于长期的热量摄入超过能量消耗而导致的能量稳态失衡。近二十年来,高脂肪饮食加上久坐不动的生活方式使肥胖已成为全球性的大流行病。

一项新研究发现,要想降低新生儿未来的肥胖风险,或许可以在母乳喂养方面“多下功夫”。

2022年7月25日,西班牙圣地亚哥联合大学的研究人员在 Nature 子刊 Nature Metabolism 上发表了题为:Prolonged breastfeeding protects from obesity by hypothalamic action of hepatic FGF21 的研究论文。

该研究发现,延长母乳喂养时间,能够避免长大后由饮食引起的肥胖,这种现象可能是因为肝脏分泌的FGF21蛋白对下丘脑的作用,下丘脑在调控机体能量消耗与利用方面起到了关键作用,这一作用增加对脂肪组织的动员和使用,同时增加能量消耗。

该研究不仅揭示了延长母乳喂养如何改变正常饮食或高脂饮食喂养的后代代谢参数,还阐明了由外周信号触发的一种预防肥胖的保护机制。 

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母体在哺乳期的营养变化对后代肥胖的影响已在动物模型中得到了广泛研究。高脂肪饮食会改变母体乳汁的成分,使后代在成年后容易出现肥胖和葡萄糖稳态失调。这种代谢功能障碍与白色脂肪组织(WAT)功能受损、棕色脂肪组织(BAT)产热活性受到抑制和下丘脑回路受损有关。虽然动物研究表明幼崽过度喂养是影响长期代谢结果的关键因素,但母乳喂养对于后代整个成年期能量稳态的影响至今尚无定论。

为了确定母乳喂养对能量稳态的重新编程是暂时的还是持续到成年期,以及哪些分子因素可能导致代谢变化。该团队建立了大鼠延长母乳喂养的模型。首先,他们观察了两组新生幼崽:一组在出生后3周断奶(SW,标准断奶组);另一组在4周断奶(DW,延迟断奶组)。然后,研究人员用正常食物或高脂肪食物喂养两组大鼠直到18周大。

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研究人员观察到,在正常食物组中,两组大鼠在体重上没有显著差异。然而,在高脂肪食物喂养的大鼠中,延迟断奶组的大鼠体重明显低于同一时期内标准断奶组的大鼠。

 

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随后,研究人员使用定量核磁共振(NMR)对大鼠身体成分分析后发现,正常食物喂养的两组大鼠具有相似的脂肪和非脂肪质量值;但在高脂肪食物喂养的大鼠中,与标准断奶组相比,延迟断奶组大鼠积累的脂肪量显著减少,但两组能量消耗的变化与活动量、呼吸商或食物摄入量的差异无关。

此外,与喂食高脂肪食物的标准断奶组相比,延迟断奶组大鼠的循环甘油三酯、胆固醇、非酯化脂肪酸和瘦素水平降低、葡萄糖耐量提高,胰岛素敏感性增强。

接下来,研究人员在热中性环境(30℃)中评估了两组高脂肪喂食的大鼠。他们发现,在食物摄入量和活动量没有差异的情况下,延迟断奶组大鼠能量消耗较高,但体重却较低。

 

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然后,他们又进行了冷暴露测试以评估棕色脂肪组织(BAT) 的产热反应,并发现延迟断奶组大鼠在4℃时比标准断奶组大鼠能更好地保持体温。

 

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这些发现表明,延长母乳喂养的时间增加了喂食高脂肪食物的动物棕色脂肪组织的产热活性以及能量消耗,从而最终以不依赖喂养的方式减少了体重增加。

最后,研究人员在该大鼠模型和转基因小鼠中进行的深入代谢表型分析表明,延长母乳喂养的影响是由成纤维细胞生长因子21(FGF21)的表达增加和伸长细胞(Tanycytes,一种神经胶质细胞)控制的下丘脑通路介导的。具体来说,FGF21激活了下丘脑外侧表达多巴胺受体2(D2R)的GABA神经元;而下丘脑在调控机体能量消耗与利脂肪用方面发挥了关键作用。

总的来说,该研究结果提出了母乳喂养通过影响肝脏-下丘脑通信和下丘脑代谢调节的长期生理变化,构成了一种预防肥胖的保护机制。此外,这些发现还为更好地理解生命早期的饮食结构对长期生理重塑的潜在机制奠定了基础。

Nature Metabolism 期刊同期发表的“新闻与观点”文章中,俄亥俄州立大学的 Elisa Félix-Soriano 和 Kristin Stanford 表示这项工作“必将在发育生物学开启新的研究,同时推动能更好理解母乳喂养长期代谢益处的临床研究”。

参考链接:

https://www.nature.com/articles/s42255-022-00602-z

https://www.nature.com/articles/s42255-022-00604-x

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    2022-09-17 liye789132251
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    2022-07-30 villahu
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    2022-07-28 ms5000001466266882

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    2022-07-28 ms3000000967837204

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