Li Rosa J W, Batchuluun Battsetseg, Zhang Song-Yang, Abraham Mona A, Wang Beini, Lim Yu-Mi, Yue Jessica T Y, Lam Tony K T
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Toronto General Hospital Research Institute, UHN, MaRS Center, TMDT 101 College Street, 10-705, Toronto, ON M5G 1L7, Canada.
iScience. 2021 Mar 26;24(4):102366. doi: 10.1016/j.isci.2021.102366. eCollection 2021 Apr 23.
Hypothalamic regulation of lipid and glucose homeostasis is emerging, but whether the dorsal vagal complex (DVC) senses nutrients and regulates hepatic nutrient metabolism remains unclear. Here, we found in rats DVC oleic acid infusion suppressed hepatic secretion of triglyceride-rich very-low-density lipoprotein (VLDL-TG), which was disrupted by inhibiting DVC long-chain fatty acyl-CoA synthetase that in parallel disturbed lipid homeostasis during intravenous lipid infusion. DVC glucose infusion elevated local glucose levels similarly as intravenous glucose infusion and suppressed hepatic glucose production. This was independent of lactate metabolism as inhibiting lactate dehydrogenase failed to disrupt glucose sensing and neither could DVC lactate infusion recapitulate glucose effect. DVC oleic acid and glucose infusion failed to lower VLDL-TG secretion and glucose production in high-fat fed rats, while inhibiting DVC farnesoid X receptor enhanced oleic acid but not glucose sensing. Thus, an impairment of DVC nutrient sensing may lead to the disruption of lipid and glucose homeostasis in metabolic syndrome.
下丘脑对脂质和葡萄糖稳态的调节作用正在逐渐显现，但背侧迷走神经复合体（DVC）是否能感知营养物质并调节肝脏营养代谢仍不清楚。在此，我们发现，给大鼠的DVC输注油酸可抑制富含甘油三酯的极低密度脂蛋白（VLDL-TG）的肝脏分泌，而抑制DVC长链脂肪酰基辅酶A合成酶会破坏这种作用，同时在静脉输注脂质期间扰乱脂质稳态。DVC输注葡萄糖与静脉输注葡萄糖类似，可提高局部葡萄糖水平并抑制肝脏葡萄糖生成。这与乳酸代谢无关，因为抑制乳酸脱氢酶未能破坏葡萄糖感知，DVC输注乳酸也无法模拟葡萄糖的作用。在高脂喂养的大鼠中，DVC输注油酸和葡萄糖未能降低VLDL-TG分泌和葡萄糖生成，而抑制DVC法尼醇X受体可增强油酸感知但不能增强葡萄糖感知。因此，DVC营养感知受损可能导致代谢综合征中脂质和葡萄糖稳态的破坏。
