Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Nat Commun. 2013;4:2316. doi: 10.1038/ncomms3316.
During fasting, animals maintain their energy balance by shifting their energy source from carbohydrates to triglycerides. However, the trigger for this switch has not yet been entirely elucidated. Here we show that a selective hepatic vagotomy slows the speed of fat consumption by attenuating sympathetic nerve-mediated lipolysis in adipose tissue. Hepatic glycogen pre-loading by the adenoviral overexpression of glycogen synthase or the transcription factor TFE3 abolished this liver-brain-adipose axis activation. Moreover, the blockade of glycogenolysis [corrected] through the knockdown of the glycogen phosphorylase gene and the resulting elevation in the glycogen content abolished the lipolytic signal from the liver, indicating that glycogen is the key to triggering this neurocircuitry. These results demonstrate that liver glycogen shortage activates a liver-brain-adipose neural axis that has an important role in switching the fuel source from glycogen to triglycerides under prolonged fasting conditions.
在禁食期间，动物通过将能量来源从碳水化合物转移到甘油三酯来维持能量平衡。然而，这种转变的触发因素尚未完全阐明。在这里，我们表明选择性肝迷走神经切断术通过减弱脂肪组织中交感神经介导的脂肪分解来减缓脂肪消耗的速度。通过腺病毒过表达糖原合酶或转录因子 TFE3 预先加载肝糖原，可消除这种肝-脑-脂肪轴的激活。此外，通过敲低糖原磷酸化酶基因阻断糖原分解[已更正]并导致糖原含量升高，可消除来自肝脏的脂肪分解信号，表明糖原是触发这种神经回路的关键。这些结果表明，肝糖原不足会激活肝-脑-脂肪神经轴，在长时间禁食期间，该神经轴在将燃料来源从糖原切换到甘油三酯方面起着重要作用。
