A low-carbohydrate ketogenic diet induces the expression of very-low-density lipoprotein receptor in liver and affects its associated metabolic abnormalities
A low-carbohydrate ketogenic diet induces the expression of very-low-density lipoprotein receptor in liver and affects its associated metabolic abnormalities
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DOI：
10.1038/s41538-019-0058-4
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发表时间：
2019-12
影响因子：
6.4
通讯作者：
T. Okuda
中科院分区：
文献类型：
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作者：
T. Okuda
低碳水化合物生酮饮食（LCKD）促进C57 BL/6野生型小鼠肝脏脂肪变性的进展，但改善瘦素缺乏型肥胖（ob/ob）小鼠的状况。在这里，我们展示了LCKD的一种新效应，与这些小鼠的相互冲突的效应相关。基因表达微阵列分析表明，在LCKD-fedob/ob小鼠中诱导了编码极低密度脂蛋白受体（VLDLR）的Vldlr基因的表达。尽管VLDLR在肝脏中不正常表达，但LCKD导致bothob/oband野生型小鼠中VLDLR表达。为了阐明这种对VLDL动力学的影响，我们分析了血清脂蛋白的脂质含量，发现仅在LCKD喂养的野生型小鼠中VLDL-甘油三酯显著降低。进一步的分析表明，甘油三酯通过VLDL从肝脏转运到肝外组织被LCKD诱导的肝脏VLDLR表达抑制，但在瘦素缺乏的条件下获救。
A low-carbohydrate ketogenic diet (LCKD) promotes the progression of hepatic steatosis in C57BL/6 wild-type mice, but improves the condition in leptin-deficient obese (ob/ob) mice. Here, we show a novel effect of LCKD associated with the conflicting effects on these mice. Gene expression microarray analyses showed that expression of theVldlrgene, which encodes the very-low-density lipoprotein receptor (VLDLR), was induced in LCKD-fedob/obmice. Although the VLDLR is not normally expressed in the liver, the LCKD led to VLDLR expression in bothob/oband wild-type mice. To clarify this effect on VLDL dynamics, we analyzed the lipid content of serum lipoproteins and found a marked decrease in VLDL-triglycerides only in LCKD-fed wild-type mice. Further analyses suggested that transport of triglycerides via VLDL from the liver to extrahepatic tissues was inhibited by LCKD-induced hepatic VLDLR expression, but rescued under conditions of leptin deficiency.