Dietary cholesterol reverses resistance to diet-induced weight gain in mice lacking Niemann-Pick C1-Like 1
Dietary cholesterol reverses resistance to diet-induced weight gain in mice lacking Niemann-Pick C1-Like 1
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DOI：
10.1194/jlr.m008599
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发表时间：
2010-10-01
影响因子：
6.5
通讯作者：
Yu, Liqing
中科院分区：
文献类型：
--
作者：
Jia, Lin;Ma, Yinyan;Yu, Liqing
Niemann-Pick C1-Like 1 (NPC1L1) 介导肠道胆固醇吸收。最近的一项研究表明，NPC1L1 敲除 (L1-KO) 小鼠对高脂饮食 (HFD) 诱导的肥胖具有抵抗力，这与其他几项研究相反。这些研究中对膳食成分的仔细比较表明膳食胆固醇在调节体重增加方面具有潜在作用。为了检验这种潜力，野生型 (WT) 和 L1-KO 小鼠被喂食三组饮食中的一组，持续时间不同：(1) 不添加胆固醇的 HFD 5 周； (2)添加或不添加胆固醇的高碳水化合物饮食5周； (3) 合成 HFD，添加或不添加胆固醇，持续 18 周。我们发现，只有在不添加胆固醇的饮食中，L1-KO 小鼠才能免受饮食引起的体重增加，而在含有 0.16% 或 0.2% (w/w) 胆固醇的饮食中则不然，胆固醇含量与典型的西方饮食相似，无论饮食的主要能量来源如何。两种基因型的食物摄入量和肠道脂肪吸收相似。 L1-KO小鼠肠道胆固醇吸收被阻断，粪便胆固醇排泄增加。在所有饮食下，L1-KO 小鼠均免受肝脂肪变性的影响。总之，增加膳食胆固醇可以恢复缺乏 NPC1L1 依赖性胆固醇吸收的小鼠的饮食引起的体重增加。-Jia，L.，Y. Ma，G. Liu，和 L. Yu。膳食胆固醇可逆转缺乏 Niemann-Pick C1-Like 1 的小鼠对饮食引起的体重增加的抵抗力。 J. Lipid Res。 2010。51：3024-3033。
Niemann-Pick C1-Like 1 (NPC1L1) mediates intestinal cholesterol absorption. NPC1L1 knockout (L1-KO) mice were recently shown to be resistant to high-fat diet (HFD)-induced obesity in one study, which was contrary to several other studies. Careful comparison of dietary compositions in these studies implies a potential role of dietary cholesterol in regulating weight gain. To examine this potential, wild-type (WT) and L1-KO mice were fed one of three sets of diets for various durations: (1) a HFD without added cholesterol for 5 weeks; (2) a high-carbohydrate diet with or without added cholesterol for 5 weeks; or (3) a synthetic HFD with or without added cholesterol for 18 weeks. We found that L1-KO mice were protected against diet-induced weight gain only on a diet without added cholesterol but not on a diet containing 0.16% or 0.2% (w/w) cholesterol, an amount similar to a typical Western diet, regardless of the major energy source of the diet. Food intake and intestinal fat absorption were similar between the two genotypes. Intestinal cholesterol absorption was blocked, and fecal cholesterol excretion increased in L1-KO mice. Under all diets, L1-KO mice were protected from hepatosteatosis. In conclusion, increasing dietary cholesterol restores diet-induced weight gain in mice deficient in NPC1L1-dependent cholesterol absorption.-Jia, L., Y. Ma, G. Liu, and L. Yu. Dietary cholesterol reverses resistance to diet-induced weight gain in mice lacking Niemann-Pick C1-Like 1. J. Lipid Res. 2010. 51: 3024-3033.