Abstract：
Lipids from cow milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for neurodevelopment, cognitive maintenance and human health in general. Nevertheless, it is largely unknown whether intake of infant formulas and medical nutrition products rich in these particles promote accretion of specific lipids and whether this affects metabolic homeostasis. To address this, we carried out a 16-week dietary intervention study where mice were supplemented with a MFGM/EV-rich concentrate, a control diet supplemented with a whey protein concentrate and devoid of milk lipids, or regular chow. Assessment of commonly used markers of metabolic health, including body weight, glucose intolerance and liver microanatomy, demonstrated no differences across the dietary regimes. In contrast, in-depth lipidomic analysis revealed accretion of milk-derived very long odd-chain sphingomyelins and ceramides in blood plasma and multiple tissues of mice fed the MFGM/EV diet. Furthermore, lipidomic flux analysis uncovered that mice fed the MFGM/EV diet have increased lipid metabolic turnover at the whole-body level. These findings help fill a long-lasting knowledge gap between the intake of MFGM/EV-containing foods and the health-promoting effects of their lipid constituents. In addition, the findings suggest that dietary sphingomyelins or ceramide-breakdown products with very long-chains can be used as structural components of cellular membranes, lipoprotein particles and signaling molecules that modulate metabolic homeostasis and health.
摘要：
来自牛乳脂肪球膜（MFGM）和细胞外囊泡（EV）的脂质被认为对神经发育有益，认知维护和人类健康。然而，摄入富含这些颗粒的婴儿配方奶粉和医学营养产品是否会促进特定脂质的增加，以及这是否会影响代谢稳态，这在很大程度上是未知的。为了解决这个问题，我们进行了一项为期16周的饮食干预研究，其中小鼠补充了富含MFGM/EV的浓缩物，补充乳清蛋白浓缩物和缺乏乳脂的对照饮食，或者普通的食物。评估常用的代谢健康标志物，包括体重,葡萄糖不耐受和肝脏显微解剖学，显示出不同的饮食制度没有差异。相比之下,深入的脂质组学分析显示，饲喂MFGM/EV饮食的小鼠的血浆和多个组织中增加了牛奶来源的超长奇数链鞘磷脂和神经酰胺。此外，脂质组学通量分析发现，饲喂MFGM/EV饮食的小鼠在全身水平上的脂质代谢周转增加。这些发现有助于填补含MFGM/EV食品的摄入量与其脂质成分的健康促进作用之间的长期知识空白。此外,研究结果表明，膳食鞘磷脂或神经酰胺分解产物具有非常长的链可以用作细胞膜的结构成分，脂蛋白颗粒和信号分子，调节代谢稳态和健康。
