Apolipoprotein A-IV enhances fatty acid uptake by adipose tissues of male mice via sympathetic activation.
Apolipoprotein A-IV enhances fatty acid uptake by adipose tissues of male mice via sympathetic activation.
复制标题
DOI：
10.1210/endocr/bqaa042
复制
发表时间：
2020-03
期刊：
影响因子：
4.8
通讯作者：
Qi Zhu;Jonathan Weng;Minqian Shen;J. Fish;Z. Shen;Karen T Coschigano;W. Davidson;P. Tso;Haifei Shi;Chunmin C Lo
中科院分区：
文献类型：
--
作者：
Qi Zhu;Jonathan Weng;Minqian Shen;J. Fish;Z. Shen;Karen T Coschigano;W. Davidson;P. Tso;Haifei Shi;Chunmin C Lo
肠道合成的载脂蛋白 A-IV (ApoA-IV) 调节脂质代谢。脂肪组织的交感神经支配也控制脂质代谢。我们假设 ApoA-IV 需要交感神经支配来增加脂肪组织对脂肪酸 (FA) 的摄取和棕色脂肪组织 (BAT) 的产热作用。在标准饲料或高脂饮食 (HFD) 喂养 3 周后，单侧脂肪组织去神经的小鼠接受腹膜内施用重组 ApoA-IV 蛋白和静脉输注含有放射性三油酸甘油酯的脂质混合物。在食物喂养的小鼠中，ApoA-IV 给药增加了完整 BAT 的 FA 摄取，但不增加对侧去神经 BAT 或完整白色脂肪组织 (WAT) 的 FA 摄取。免疫印迹显示，在食物喂养的小鼠中，ApoA-IV 增加了完整 BAT 和腹股沟 WAT (IWAT) 中脂蛋白脂肪酶 (LPL) 和酪氨酸羟化酶 (TH) 的表达；而 ApoA-IV 仅增强完整 BAT 中的 β3 肾上腺素能受体 (β3-AR)、脂肪甘油三酯脂肪酶 (ATGL) 和解偶联蛋白 1 (UCP1) 的蛋白质水平。在 HFD 喂养的小鼠中，ApoA-IV 提高了完整附睾 WAT (EWAT) 的 FA 摄取，但不提高完整 BAT 或 IWAT 的 FA 摄取。 ApoA-IV 增加了食物喂养小鼠 BAT 和 EWAT 中去甲肾上腺素周转率 (NETO) 的交感活性，而仅提高了 HFD 喂养小鼠 EWAT 中的 NETO。这些观察结果表明，在食物喂养的小鼠中，ApoA-IV 激活 BAT 的交感活性，并通过神经支配增加 BAT 对 FA 的摄取，而在 HFD 喂养的小鼠中，ApoA-IV 刺激 EWAT 的交感活性，将 FA 分流到 EWAT 中。
Apolipoprotein A-IV (ApoA-IV) synthesized by the gut regulates lipid metabolism. Sympathetic innervation of adipose tissues also controls lipid metabolism. We hypothesized that ApoA-IV required sympathetic innervation to increase fatty acid (FA) uptake by adipose tissues and brown adipose tissue (BAT) thermogenesis. After 3 weeks feeding of either a standard chow diet or a high-fat diet (HFD), mice with unilateral denervation of adipose tissues received intraperitoneal administration of recombinant ApoA-IV protein and intravenous infusion of lipid mixture with radioactive triolein. In chow-fed mice, ApoA-IV administration increased FA uptake by intact BAT, but not the contralateral denervated BAT or intact white adipose tissue (WAT). Immunoblots showed that, in chow-fed mice, ApoA-IV increased expression of lipoprotein lipase (LPL) and tyrosine hydroxylase (TH) in both intact BAT and inguinal WAT (IWAT); while ApoA-IV enhanced protein levels of β3 adrenergic receptor (β3-AR), adipose triglyceride lipase (ATGL), and uncoupling protein 1 (UCP1) in the intact BAT only. In HFD-fed mice, ApoA-IV elevated FA uptake by intact epididymal WAT (EWAT), but not intact BAT or IWAT. ApoA-IV increased sympathetic activity assessed by norepinephrine turnover (NETO) rate in BAT and EWAT of chow-fed mice, whereas it elevated NETO only in EWAT of HFD-fed mice. These observations suggest that, in chow-fed mice, ApoA-IV activates sympathetic activity of BAT and increases FA uptake by BAT via innervation, while in HFD-fed mice, ApoA-IV stimulates sympathetic activity of EWAT to shunt FAs into the EWAT.