LXRs regulate the balance between fat storage and oxidation
LXRs regulate the balance between fat storage and oxidation
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DOI：
10.1016/j.cmet.2005.03.001
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发表时间：
2005-04-01
期刊：
影响因子：
29
通讯作者：
Mangelsdorf, DJ
中科院分区：
文献类型：
--
作者：
Kalaany, NY;Gauthier, KC;Mangelsdorf, DJ
尽管肝脏X受体（LXRs）在调节胆固醇稳态中的作用已经确立，但它们在脂质稳态中的作用仍不清楚。在这里，我们发现LXR缺失的小鼠在肝脏脂质代谢方面存在缺陷，并且在含有高脂肪和高胆固醇的饮食中抵抗肥胖。这种表型依赖于膳食胆固醇的存在，并伴随着肝脏中甲状腺激素的异常产生。有趣的是，LXR-/-小鼠无法诱导SREBP-1c依赖的脂肪生成并不能解释LXR-/-表型，因为SREBP-1c缺失的小鼠不耐肥胖。相反，LXR-/-反应是由于肌肉和白色脂肪中不偶联的氧化磷酸化和不偶联蛋白的异位表达引起的异常能量耗散。这些研究表明，通过选择性地感知富含脂质的饮食中的胆固醇成分，LXRs控制着膳食脂肪储存和氧化之间的平衡。
Despite the well-established role of liver X receptors (LXRs) in regulating cholesterol homeostasis, their contribution to lipid homeostasis remains unclear. Here we show that LXR null mice are defective in hepatic lipid metabolism and are resistant to obesity when challenged with a diet containing both high fat and cholesterol. This phenotype is dependent on the presence of dietary cholesterol and is accompanied by the aberrant production of thyroid hormone in liver. Interestingly, the inability of LXR-/- mice to induce SREBP-1c-dependent lipogenesis does not explain the LXR-/- phenotype, since SREBP-1c null mice are not obesity resistant. Instead, the LXR-/- response is due to abnormal energy dissipation resulting from uncoupled oxidative phosphorylation and ectopic expression of uncoupling proteins in muscle and white adipose. These studies suggest that, by selectively sensing the cholesterol component of a lipid-rich diet, LXRs govern the balance between storage and oxidation of dietary fat.