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

• Published in: Gut Vol. 67; no. 7; pp. 1269 - 1279
• Main Authors: Li, Zhuang, Yi, Chun-Xia, Katiraei, Saeed, Kooijman, Sander, Zhou, Enchen, Chung, Chih Kit, Gao, Yuanqing, van den Heuvel, José K, Meijer, Onno C, Berbée, Jimmy F P, Heijink, Marieke, Giera, Martin, Willems van Dijk, Ko, Groen, Albert K, Rensen, Patrick C N, Wang, Yanan
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.07.2018
• Subjects: Acute effects; Adipose tissue; Adipose tissue (brown); Appetite; Body fat; Brain stem; Clinical medicine; Diabetes; Diet; Dietary supplements; Energy; Energy expenditure; Energy intake; Energy metabolism; Epigenetics; Fatty acids; Fatty liver; Food; Food intake; Gastrointestinal surgery; High fat diet; Hypothalamus; Insulin resistance; Intravenous administration; Metabolic syndrome; Nervous system; Neuropeptide Y; Obesity; Oxidation; Rodents; Satiety; Solitary tract nucleus; Steatosis; Studies; Vagotomy; Vagus nerve; Weight control; appetite; brain/gut interaction; short-chain fatty acids; energy metabolism; obesity
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2017-314050

ObjectiveButyrate 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.DesignAcute 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.ResultsAcute 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.ConclusionButyrate acts on the gut-brain neural circuit to improve energy metabolism via reducing energy intake and enhancing fat oxidation by activating BAT.