Brown adipose tissue (BAT) thermogenesis is activated by feeding. Recently, we revealed a secretin-mediated gut–BAT–brain axis, which stimulates satiation in mice, but the purpose of meal-induced BAT activation in humans has been unclear. In this placebo-controlled, randomized crossover study, we investigated the effects of intravenous secretin on BAT metabolism (measured with [¹⁸F]FDG and [¹⁵O]H₂O positron emission tomography) and appetite (measured with functional magnetic resonance imaging) in healthy, normal weight men (GUTBAT trial no. NCT03290846). Participants were blinded to the intervention. Secretin increased BAT glucose uptake (primary endpoint) compared to placebo by 57% (median (interquartile range, IQR), 0.82 (0.77) versus 0.59 (0.53) μmol per 100 g per min, 95% confidence interval (CI) (0.09, 0.89), P = 0.002, effect size r = 0.570), while BAT perfusion remained unchanged (mean (s.d.) 4.73 (1.82) versus 6.14 (3.05) ml per 100 g per min, 95%CI (−2.91, 0.07), P = 0.063, effect size d = −0.549) (n = 15). Whole body energy expenditure increased by 2% (P = 0.011) (n = 15). Secretin attenuated blood-oxygen level-dependent activity (primary endpoint) in brain reward circuits during food cue tasks (significance level false discovery rate corrected at P = 0.05) (n = 14). Caloric intake did not significantly change, but motivation to refeed after a meal was delayed by 39 min (P = 0.039) (n = 14). No adverse effects were detected. Here we show in humans that secretin activates BAT, reduces central responses to appetizing food and delays the motivation to refeed after a meal. This suggests that meal-induced, secretin-mediated BAT activation is relevant in the control of food intake in humans. As obesity is increasing worldwide, this appetite regulating axis offers new possibilities for clinical research in treating obesity.

棕色脂肪组织 (BAT) 产热是通过喂食激活的。最近，我们揭示了促胰液素介导的肠-BAT-脑轴，它可以刺激小鼠的饱腹感，但膳食诱导 BAT 在人类中激活的目的尚不清楚。在这项安慰剂对照的随机交叉研究中，我们调查了静脉注射分泌素对 BAT 代谢的影响（用 [ ¹⁸ F]FDG 和 [ ¹⁵ O]H _2测量O 正电子发射断层扫描）和食欲（用功能性磁共振成像测量）健康、正常体重的男性（GUTBAT 试验编号 NCT03290846）。参与者对干预不知情。与安慰剂相比，分泌素增加 BAT 葡萄糖摄取（主要终点）57%（中位数（四分位数间距，IQR），0.82 (0.77) 对比 0.59 (0.53) μmol 每 100 g/min，95% 置信区间 (CI) (0.09, 0.89），P  = 0.002，效应量r  = 0.570），而 BAT 灌注保持不变（平均（标准差）4.73（1.82）对比 6.14（3.05）毫升每 100 克每分钟，95%CI（-2.91，0.07），P  = 0.063，效应大小d  = −0.549)（n  = 15）。全身能量消耗增加 2% ( P  = 0.011) (n  = 15). 在食物提示任务期间，分泌素减弱了大脑奖励回路中的血氧水平依赖性活动（主要终点）（显着性水平错误发现率在P  = 0.05 时校正）（n  = 14）。热量摄入没有显着变化，但饭后重新进食的动机延迟了 39 分钟 ( P  = 0.039) ( n = 14). 没有检测到不良反应。在这里，我们在人类身上展示了分泌素激活 BAT，减少了对开胃食物的中枢反应，并延迟了饭后重新进食的动机。这表明膳食诱导的、分泌素介导的 BAT 激活与人类食物摄入的控制相关。随着世界范围内肥胖症的增加，这种食欲调节轴为治疗肥胖症的临床研究提供了新的可能性。