Role of FAT/CD36 in fatty acid sensing, energy, and glucose homeostasis regulation in DIO and DR rats
Role of FAT/CD36 in fatty acid sensing, energy, and glucose homeostasis regulation in DIO and DR rats
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DOI：
10.1152/ajpregu.00367.2014
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发表时间：
2015-02-01
影响因子：
2.8
通讯作者：
Levin, Barry E.
中科院分区：
文献类型：
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作者：
Le Foll, Christelle;Dunn-Meynell, Ambrose A.;Levin, Barry E.
下丘脑脂肪酸 (FA) 传感神经元利用 FA 易位器/受体 FAT/CD36 改变其活性。用表达 CD36 shRNA (AAV CD36 shRNA) 的腺相关病毒载体消除腹内侧下丘脑 (VMH) CD36 会导致近交系大鼠脂肪储存的重新分配和胰岛素抵抗。本研究评估了使用 VMH AAV CD36 shRNA 注射选择性饲养饮食诱导肥胖 (DIO) 和饮食抗性 (DR) 大鼠的出生后第 5 天 (P5) 和 P21 中 VMH CD36 介导的 FA 传感对能量和葡萄糖稳态调节的需求。 P5 CD36 耗竭主要改变 DIO 大鼠的 VMH 神经元 FA 感知。采用 45% 脂肪饮食 10 周后，在 P21 注射 VMH AAV CD36 shRNA 的 DIO 大鼠比 DIO AAV 对照组吃得更多，体重增加更多，而注射 DR AAV CD36 shRNA 的大鼠比 DR AAV 对照组体重增加更少。 VMH CD36 耗竭增加了 DIO 和 DR 大鼠的腹股沟脂肪垫重量和瘦素水平。尽管注射 DR AAV CD36 shRNA 的大鼠变得与 DIO AAV 对照组一样肥胖，但只有 DIO 对照组和 CD36 耗尽的大鼠在 45% 脂肪饮食下出现胰岛素抵抗。 VMH CD36 耗竭会阻碍 DIO 和 DR 大鼠的线性生长。在 P5 注射 AAV CD36 shRNA 的 DIO 大鼠脂肪量增加，主要是由于皮下脂肪增加了 45%。他们还存在胰岛素抵抗，肝脏甘油三酯增加了 71%。这些结果表明，VMH CD36 介导的 FA 传感是调节 DIO 和 DR 大鼠能量和葡萄糖稳态以及脂肪沉积的关键因素。
Hypothalamic fatty acid (FA) sensing neurons alter their activity utilizing the FA translocator/receptor, FAT/CD36. Depletion of ventromedial hypothalamus (VMH) CD36 with adeno-associated viral vector expressing CD36 shRNA (AAV CD36 shRNA) leads to redistribution of adipose stores and insulin resistance in outbred rats. This study assessed the requirement of VMH CD36-mediated FA sensing for the regulation of energy and glucose homeostasis in postnatal day 5 (P5) and P21 selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats using VMH AAV CD36 shRNA injections. P5 CD36 depletion altered VMH neuronal FA sensing predominantly in DIO rats. After 10 wk on a 45% fat diet, DIO rats injected with VMH AAV CD36 shRNA at P21 ate more and gained more weight than DIO AAV controls, while DR AAV CD36 shRNA-injected rats gained less weight than DR AAV controls. VMH CD36 depletion increased inguinal fat pad weights and leptin levels in DIO and DR rats. Although DR AAV CD36 shRNA-injected rats became as obese as DIO AAV controls, only DIO control and CD36 depleted rats became insulin-resistant on a 45% fat diet. VMH CD36 depletion stunted linear growth in DIO and DR rats. DIO rats injected with AAV CD36 shRNA at P5 had increased fat mass, mostly due to a 45% increase in subcutaneous fat. They were also insulin-resistant with an associated 71% increase of liver triglycerides. These results demonstrate that VMH CD36-mediated FA sensing is a critical factor in the regulation of energy and glucose homeostasis and fat deposition in DIO and DR rats.