High fat diet activates adult mouse lung stem cells and accelerates several aging-induced effects
High fat diet activates adult mouse lung stem cells and accelerates several aging-induced effects
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DOI：
10.1016/j.scr.2018.10.006
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发表时间：
2018-12-01
影响因子：
1.2
通讯作者：
Betsuyaku, Tomoko
中科院分区：
文献类型：
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作者：
Hegab, Ahmed E.;Ozaki, Mani;Betsuyaku, Tomoko
高脂饮食（HFD）降低小鼠的寿命，并且是多种人类疾病的危险因素。在这里，我们研究了HFD对肺上皮细胞和干细胞的影响及其与衰老的相互作用。用标准饮食（SD）或HFD喂养年轻和年老小鼠，然后检查它们的气管和肺的组织学变化、炎症和线粒体功能。使用体外类器官/集落形成效率（CFE）测定来检查它们的干细胞功能。衰老减少了气管基底和肺泡2型（AT 2）细胞的数量。HFD显著增加AT 2细胞的数量。衰老也会导致肺部炎症的显著增加，而HFD在年轻小鼠中也会导致类似的增加。衰老降低了线粒体的质量和功能，并增加了活性氧。在年轻小鼠中，HFD引起的线粒体变化类似于衰老引起的变化。与SD喂养的小鼠相比，从年轻和年老的HFD喂养的小鼠收集的气管和肺上皮细胞的类器官培养物显示出更高的CFE。将HFD转换为低热量/脂肪饮食（LCD）有效地逆转了几种HFD诱导的效应。因此，HFD诱导肺中的几种组织学、炎症和功能变化，并加剧衰老诱导的肺部炎症和线粒体退化。LCD可以逆转许多HFD引起的效应。
High fat diet (HFD) decreases the lifespan of mice, and is a risk factor for several human diseases. Here, we investigated the effects of a HFD on lung epithelial and stem cells and its interaction with aging. Young and old mice were fed with either a standard diet (SD) or a HFD then their trachea and lung were examined for histological changes, inflammation, and mitochondrial function. Their stem cell function was examined using the in vitro organoid/colony forming efficiency (CFE) assay. Aging reduced the number of tracheal basal and alveolar type-2 (AT2) cells. HFD significantly increased the number of AT2 cells. Aging also caused a significant increase in lung inflammation, and HFD caused a similar increase, in young mice. Aging reduced mitochondrial mass and function, and increased reactive oxygen species. In young mice, HFD caused mitochondrial changes similar to the aging-induced changes. Organoid culture of tracheal and lung epithelial cells collected from both young and old HFD-fed mice showed higher CFE compared to SD-fed mice. Switching the HFD to low calorie/fat diet (LCD) efficiently reversed several of the HFD-induced effects. Thus, HFD induces several histological, inflammatory, and functional changes in the lung, and exacerbates the aging-induced lung inflammation and mitochondrial deterioration. LCD can reverse many of the HFD-induced effects.