Department of Physiology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, 3010, VIC, Australia; Metabolic Disease, Obesity and Diabetes Program, Biomedicine Discovery Institute and the Department of Physiology, Monash University, Clayton, 3800, VIC, Australia.
Metabolic Disease, Obesity and Diabetes Program, Biomedicine Discovery Institute and the Department of Physiology, Monash University, Clayton, 3800, VIC, Australia; Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Mol Metab. 2020 Apr;34:54-71. doi: 10.1016/j.molmet.2020.01.002. Epub 2020 Jan 9.
Nutrient sensing by hypothalamic neurons is critical for the regulation of food intake and energy expenditure. We aimed to identify long- and medium-chain fatty acid species transported into the brain, their effects on energy balance, and the mechanisms by which they regulate activity of hypothalamic neurons.
Simultaneous blood and cerebrospinal fluid (CSF) sampling was undertaken in rats and metabolic analyses using radiolabeled fatty acid tracers were performed on mice. Electrophysiological recording techniques were used to investigate signaling mechanisms underlying fatty acid-induced changes in activity of pro-opiomelanocortin (POMC) neurons.
Medium-chain fatty acid (MCFA) octanoic acid (C8:0), unlike long-chain fatty acids, was rapidly transported into the hypothalamus of mice and almost exclusively oxidized, causing rapid, transient reductions in food intake and increased energy expenditure. Octanoic acid differentially regulates the excitability of POMC neurons, activating these neurons directly via GPR40 and inducing inhibition via an indirect non-synaptic, purine, and adenosine receptor-dependent mechanism.
MCFA octanoic acid is a central signaling nutrient that targets POMC neurons via distinct direct and indirect signal transduction pathways to instigate changes in energy status. These results could explain the beneficial health effects that accompany MCFA consumption.
下丘脑神经元对营养物质的感应对于调节食物摄入和能量消耗至关重要。我们旨在确定进入大脑的长链和中链脂肪酸种类、它们对能量平衡的影响，以及它们调节下丘脑神经元活动的机制。
在大鼠中进行同时的血液和脑脊液（CSF）采样，并在小鼠中使用放射性标记的脂肪酸示踪剂进行代谢分析。使用电生理记录技术研究脂肪酸诱导的 POMC 神经元活动变化的信号机制。
与长链脂肪酸不同，中链脂肪酸（MCFA）辛酸（C8:0）迅速被转运到小鼠的下丘脑，并几乎完全被氧化，导致食物摄入迅速、短暂减少和能量消耗增加。辛酸通过 GPR40 直接调节 POMC 神经元的兴奋性，并通过间接的非突触、嘌呤和腺苷受体依赖的机制诱导抑制。
MCFA 辛酸是一种中枢信号营养物质，通过独特的直接和间接信号转导途径靶向 POMC 神经元，引发能量状态的变化。这些结果可以解释伴随 MCFA 消耗的有益健康影响。
