丁酸盐通过肠-脑神经回路降低食欲并激活褐色脂肪组织

Title：
Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit

DOI：
10.1136/gutjnl-2017-314050

Abstract：
Butyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what extent these two components contribute to the beneficial metabolic effects of butyrate.Acute effects of butyrate on appetite and its method of action were investigated in mice following an intragastric gavage or intravenous injection of butyrate. To study the contribution of satiety to the metabolic benefits of butyrate, mice were fed a high-fat diet with butyrate, and an additional pair-fed group was included. Mechanistic involvement of the gut-brain neural circuit was investigated in vagotomised mice.Acute oral, but not intravenous, butyrate administration decreased food intake, suppressed the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus, and decreased neuronal activity within the nucleus tractus solitarius and dorsal vagal complex in the brainstem. Chronic butyrate supplementation prevented diet-induced obesity, hyperinsulinaemia, hypertriglyceridaemia and hepatic steatosis, largely attributed to a reduction in food intake. Butyrate also modestly promoted fat oxidation and activated brown adipose tissue (BAT), evident from increased utilisation of plasma triglyceride-derived fatty acids. This effect was not due to the reduced food intake, but explained by an increased sympathetic outflow to BAT. Subdiaphragmatic vagotomy abolished the effects of butyrate on food intake as well as the stimulation of metabolic activity in BAT.Butyrate acts on the gut-brain neural circuit to improve energy metabolism via reducing energy intake and enhancing fat oxidation by activating BAT.

All Authors：
Zhuang Li, Chun-Xia Yi, Saeed Katiraei, Sander Kooijman, Enchen Zhou, Chih Kit Chung, Yuanqing Gao, José K van den Heuvel, Onno C Meijer, Jimmy FP Berbée, Marieke Heijink, Martin Giera, Ko Willems van Dijk, Albert K Groen, Patrick CN Rensen, Yanan Wang

First Authors：
Zhuang Li

Correspondence：
Yanan Wang

内容要点：

本研究通过向高脂饮食小鼠的食物中添加5%丁酸钠，喂食9周的处理，发现口服而非静脉注射丁酸盐，可抑制下丘脑中促进食欲的神经元活性，减少食物摄入，预防饮食引发的肥胖、血脂异常、胰岛素抵抗和脂肪肝。 并促进脂肪氧化，经交感神经激活褐色脂肪组织，增强其代谢产热能力。这些作用依赖于肠-脑神经回路，即迷走神经通路。丁酸盐摄入还可改变肠道菌群构成，提高厚壁菌门丰度，尤其是产芽胞菌。口服补充丁酸盐，或可用于防治肥胖及相关的心血管代谢疾病。