CD36 deficiency impairs intestinal lipid secretion and clearance of chylomicrons from the blood.
CD36 deficiency impairs intestinal lipid secretion and clearance of chylomicrons from the blood.
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DOI：
10.1172/jci21514
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发表时间：
2005-05
期刊：
影响因子：
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通讯作者：
V. Drover;M. Ajmal;F. Nassir;N. Davidson;Andromeda M. Nauli;D. Sahoo;P. Tso;N. Abumrad
中科院分区：
文献类型：
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作者：
V. Drover;M. Ajmal;F. Nassir;N. Davidson;Andromeda M. Nauli;D. Sahoo;P. Tso;N. Abumrad
CD 36介导脂肪酸（FA）穿过肌肉和脂肪细胞质膜的转移，从而在体内调节外周FA代谢方面发挥重要作用。在近端肠中，CD 36大量定位于上皮细胞的顶端表面，其模式类似于涉及膳食FA摄取的其他蛋白质。为了确定CD 36在肠道中的作用，我们研究了WT和CD 36缺失小鼠对急性和慢性脂肪喂养的FA利用和脂蛋白分泌。通过管饲法给予脂肪团或喂食高脂肪饮食的CD 36-null小鼠在近端肠中积累中性脂质，这表明脂质加工异常。使用小鼠配备淋巴瘘的模型，我们通过直接测量脂质输出获得了脂蛋白分泌缺陷的证据。分泌缺陷似乎反映了CD 36-null肠细胞在内质网中从膳食FA有效合成三酰甘油的能力受损。在完整小鼠的血浆中，小肠脂质分泌减少被精氨酸衍生脂蛋白的缓慢清除所掩盖。尽管脂蛋白脂肪酶活性正常，但清除率受损，这可能反映了脂肪酶被脂肪酸反馈抑制，因为脂肪酸从血浆中的清除有缺陷。我们的结论是，CD 36是重要的分泌和肠道脂蛋白的清除。CD 36缺乏导致餐后和空腹状态下的高甘油三酯血症，并且在人类中可能构成饮食诱导的2型糖尿病和心血管疾病的风险因素。
CD36 mediates the transfer of fatty acids (FAs) across the plasma membranes of muscle and adipose cells, thus playing an important role in regulating peripheral FA metabolism in vivo. In the proximal intestine, CD36 is localized in abundant quantities on the apical surface of epithelial cells, a pattern similar to that of other proteins implicated in the uptake of dietary FAs. To define the role of CD36 in the intestine, we examined FA utilization and lipoprotein secretion by WT and CD36-null mice in response to acute and chronic fat feeding. CD36-null mice given a fat bolus by gavage or fed a high-fat diet accumulated neutral lipid in the proximal intestine, which indicated abnormal lipid processing. Using a model in which mice were equipped with lymph fistulae, we obtained evidence of defective lipoprotein secretion by directly measuring lipid output. The secretion defect appeared to reflect an impaired ability of CD36-null enterocytes to efficiently synthesize triacylglycerols from dietary FAs in the endoplasmic reticulum. In the plasma of intact mice, the reduced intestinal lipid secretion was masked by slow clearance of intestine-derived lipoproteins. The impaired clearance occurred despite normal lipoprotein lipase activity and likely reflected feedback inhibition of the lipase by FAs due to their defective removal from the plasma. We conclude that CD36 is important for both secretion and clearance of intestinal lipoproteins. CD36 deficiency results in hypertriglyceridemia both in the postprandial and fasting states and in humans may constitute a risk factor for diet-induced type 2 diabetes and cardiovascular disease.