Protection from obesity in mice lacking the VLDL receptor
Protection from obesity in mice lacking the VLDL receptor
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DOI：
10.1161/hq0901.095147
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发表时间：
2001-09-01
影响因子：
8.7
通讯作者：
Jong, MC
中科院分区：
文献类型：
--
作者：
Goudriaan, JR;Tacken, PJ;Jong, MC
先前已经报道，缺乏VLDL受体（VLDLR-/-）的小鼠表现出正常的血浆脂质水平和脂肪组织质量的适度降低。在本研究中，在小鼠中研究了VLDLR缺乏对深度体重增加的影响。通过喂食高脂肪、高热量（HFC）饮食或通过将小鼠与遗传肥胖ob/ob背景杂交来诱导肥胖。在HFC喂养17周后，VLDLR-/-小鼠保持瘦，而它们的野生型同窝小鼠（VLDLR+/+）变得肥胖。类似地，在不存在VLDLR的情况下，ob/ob小鼠的体重增加不太明显。此外，VLDLR缺乏导致HFC喂养后血浆甘油三酯增加。VLDLR-/-小鼠的肥胖保护涉及外周脂肪酸摄取减少，因为VLDLR-/-小鼠表现出全身游离脂肪酸摄取显著减少，食物摄入和脂肪吸收无明显差异。这些观察结果得到了两种肥胖模型的VLDLR-/-小鼠中平均脂肪细胞大小强烈降低的支持，这意味着在不存在VLDLR的情况下脂肪细胞甘油三酯储存减少。这些结果表明，VLDLR在将VLDL衍生的脂肪酸递送到脂肪组织中中起作用。
It has previously been reported that mice lacking the VLDL receptor (VLDLR-/-) exhibit normal plasma lipid levels and a modest decrease in adipose tissue mass. In the present study, the effect of VLDLR deficiency on profound weight gain was studied in mice. Obesity was induced either by feeding of a high-fat, high-calorie (HFC) diet or by crossbreeding mice onto the genetically obese ob/ob background. After 17 weeks of HFC feeding, VLDLR-/- mice remained lean, whereas their wild-type littermates (VLDLR+/+) became obese. Similarly, the weight gain of ob/ob mice was less profound in the absence of the VLDLR. Moreover, VLDLR deficiency led to increased plasma triglycerides after HFC feeding. The protection from obesity in VLDLR-/- mice involved decreased peripheral uptake of fatty acids, because VLDLR-/- mice exhibited a significant reduction in whole-body free fatty acid uptake, with no clear differences in food intake and fat absorption. These observations were supported by a strong decrease in average adipocyte size in VLDLR-/- mice of both obesity models, implying reduced adipocyte triglyceride storage in the absence of the VLDLR. These results suggest that the VLDLR plays a role in the delivery of VLDL-derived fatty acids into adipose tissue.