Targeting the Liver-Brain Axis with Hop-Derived Flavonoids Improves Lipid Metabolism and Cognitive Performance in Mice.
Targeting the Liver-Brain Axis with Hop-Derived Flavonoids Improves Lipid Metabolism and Cognitive Performance in Mice.
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DOI：
10.1002/mnfr.202000341
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发表时间：
2020-08
影响因子：
5.2
通讯作者：
Stevens JF
中科院分区：
文献类型：
--
作者：
Paraiso IL;Revel JS;Choi J;Miranda CL;Lak P;Kioussi C;Bobe G;Gombart AF;Raber J;Maier CS;Stevens JF
包括神经酰胺在内的鞘脂与肥胖和胰岛素抵抗的发病机制有关。相应地，抑制促炎性和神经毒性神经酰胺积累可预防肥胖介导的胰岛素抵抗和认知障碍。越来越多的证据表明法尼醇X受体（FXR）参与神经酰胺代谢，因为胆汁酸-FXR串扰控制沿着肠-肝轴的神经酰胺水平。我们之前曾报道过，FXR激动剂黄腐酚（XN）（啤酒花（啤酒花）中主要的异戊烯化类黄酮）及其氢化衍生物α，β-二羟黄腐酚（DXN）和四羟黄腐酚（TXN）改善肥胖介导的胰岛素抵抗和认知障碍喂食高脂肪饮食（HFD）的小鼠的认知障碍。为了更好地了解黄酮类化合物如何改善两者，我们分析了肝脏中的脂质和胆汁酸谱，测量了海马中的鞘脂相对丰度，并将其与代谢和神经认知性能联系起来。XN，DXN和TXN（30 mg/kg BW/天）降低肝脏和海马中的神经酰胺含量;后者与空间学习和记忆的改善有关。此外，XN，DXN和TXN通过促进胆汁酸的从头合成来降低肝脏胆固醇含量。这些观察结果表明，XN，DXN和TXN可能通过靶向肝-脑轴来减轻肥胖引起的代谢和神经认知障碍。
Sphingolipids including ceramides are implicated in the pathogenesis of obesity and insulin resistance. Correspondingly, inhibition of pro-inflammatory and neurotoxic ceramide accumulation prevents obesity-mediated insulin resistance and cognitive impairment. Increasing evidence suggests the farnesoid X receptor (FXR) is involved in ceramide metabolism, as bile acid-FXR crosstalk controls ceramide levels along the gut-liver axis. We previously reported that FXR agonist xanthohumol (XN), the principal prenylated flavonoid in hops (Humulus lupulus), and its hydrogenated derivatives, α,β-dihydroxanthohumol (DXN) and tetrahydroxanthohumol (TXN), ameliorated obesity-mediated insulin resistance and cognitive impairment in mice fed a high-fat diet (HFD). To better understand how the flavonoids improved both, we analyzed lipid and bile acid profiles in the liver, measured sphingolipid relative abundance in the hippocampus, and linked them to metabolic and neurocognitive performance. XN, DXN and TXN (30mg/kg BW/day) decreased ceramide content in liver and hippocampus; the latter was linked to improvements in spatial learning and memory. In addition, XN, DXN and TXN decreased hepatic cholesterol content by enhancing de novo synthesis of bile acids. These observations suggest that XN, DXN and TXN may alleviate obesity-induced metabolic and neurocognitive impairments by targeting the liver-brain axis.
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影响因子：
13.6
作者：
Kim, Hee-Yong;Huang, Bill X.;Spector, Arthur A.
通讯作者：
Spector, Arthur A.
影响因子：
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de la Monte, Suzanne M.;Tong, Ming;Wands, Jack R.
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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