von Holstein-Rathlou Stephanie, BonDurant Lucas D, Peltekian Lila, Naber Meghan C, Yin Terry C, Claflin Kristin E, Urizar Adriana Ibarra, Madsen Andreas N, Ratner Cecilia, Holst Birgitte, Karstoft Kristian, Vandenbeuch Aurelie, Anderson Catherine B, Cassell Martin D, Thompson Anthony P, Solomon Thomas P, Rahmouni Kamal, Kinnamon Sue C, Pieper Andrew A, Gillum Matthew P, Potthoff Matthew J
Section for Metabolic Imaging and Liver Metabolism, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Cell Metab. 2016 Feb 9;23(2):335-43. doi: 10.1016/j.cmet.2015.12.003. Epub 2015 Dec 24.
The liver is an important integrator of nutrient metabolism, yet no liver-derived factors regulating nutrient preference or carbohydrate appetite have been identified. Here we show that the liver regulates carbohydrate intake through production of the hepatokine fibroblast growth factor 21 (FGF21), which markedly suppresses consumption of simple sugars, but not complex carbohydrates, proteins, or lipids. Genetic loss of FGF21 in mice increases sucrose consumption, whereas acute administration or overexpression of FGF21 suppresses the intake of both sugar and non-caloric sweeteners. FGF21 does not affect chorda tympani nerve responses to sweet tastants, instead reducing sweet-seeking behavior and meal size via neurons in the hypothalamus. This liver-to-brain hormonal axis likely represents a negative feedback loop as hepatic FGF21 production is elevated by sucrose ingestion. We conclude that the liver functions to regulate macronutrient-specific intake by producing an endocrine satiety signal that acts centrally to suppress the intake of "sweets."
肝脏是营养物质代谢的重要整合器官，但尚未发现有肝脏衍生因子调节营养偏好或碳水化合物食欲。在此，我们表明肝脏通过产生肝细胞因子成纤维细胞生长因子21（FGF21）来调节碳水化合物摄入，FGF21能显著抑制单糖的消耗，但不影响复合碳水化合物、蛋白质或脂质的消耗。小鼠体内FGF21基因缺失会增加蔗糖消耗量，而急性给予或过表达FGF21则会抑制糖和无热量甜味剂的摄入。FGF21不会影响鼓索神经对甜味剂的反应，而是通过下丘脑神经元减少对甜味的寻求行为和进食量。由于蔗糖摄入会使肝脏FGF21的产生增加，这种从肝脏到大脑的激素轴可能代表一种负反馈回路。我们得出结论，肝脏通过产生一种内分泌饱腹感信号来调节特定宏量营养素的摄入，该信号在中枢起作用以抑制“甜食”的摄入。
