Editors' ChoiceMetabolism

Priming the liver for a feast after famine

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Sci. Signal.  27 Nov 2018:
Vol. 11, Issue 558, eaaw1457
DOI: 10.1126/scisignal.aaw1457

Food perception activates a hypothalamus-to-liver pathway that prepares the liver for nutrient influx.

Seeing, smelling, and tasting food are sufficient to trigger physiological changes that prepare the body for food ingestion. Brandt et al. investigated the effects of sensory perception of food on the liver, which would need to adapt to an influx of nutrients and enhanced protein synthesis during refeeding. The authors used fasted mice that were refed, presented with food that they could see and smell but not eat, or presented with artificial food. Food presentation to fasted mice—whether they were allowed to eat the food or not—resulted in increased hepatic expression of spliced Xbp1, which generates a key effector in the endoplasmic reticulum (ER) stress pathway, and of Xbp1 target genes encoding factors involved in protein chaperoning or processing. In addition, the liver showed increased signaling through the kinase mechanistic target of rapamycin (mTOR), which triggers cell growth and proliferation in response to nutrient availability, and increased synthesis of phosphatidylcholines and phosphatidylethanolamines, lipids that are required to expand the ER during protein synthesis. These changes were absent in fasted mice that were not refed and/or those presented with artificial food. Proopiomelanocortin (POMC) neurons in the hypothalamus are activated by refeeding and suppress appetite. Similar to refeeding, presentation of inaccessible food activated these neurons, as shown by increased Ca2+ signaling and Fos expression. Stimulation of POMC neurons increased the splicing of Xbp1 and mTORC1 activity in the liver. These effects required melanocortin-4 receptors (MC4Rs), stimulation of hepatic sympathetic nerve activity by POMC neurons, hepatic sympathetic nerve release of norepinephrine, and α1-adrenergic receptors in hepatocytes. Thus, food perception activates a hypothalamus-to-liver pathway that prepares the liver for nutrient influx.

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