Heimbürger Sebastian M N, Bentzen Maria J, Kizilkaya Hüsün S, Hartmann Bolette, Holst Jens J, Rosenkilde Mette M, Dela Flemming, Hansen Svend H, Rehfeld Jens F, Christensen Mikkel B, Knop Filip K
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup 2900, Denmark.
Clinical Research, Steno Diabetes Center Copenhagen, Herlev 2730, Denmark.
Eur J Endocrinol. 2024 Nov 27;191(6):545-557. doi: 10.1093/ejendo/lvae147.
The hormone secretin, best known for regulating pH in the duodenum, has anorectic properties in mice proposedly mediated via secretin-induced brown adipose tissue (BAT) activation. We investigated the effects of exogenous secretin on ad libitum food intake, BAT activity, and postprandial physiology in healthy male volunteers.
In a randomized, placebo-controlled, double-blind, crossover study, 25 healthy men underwent two 5-h i.v. infusions of secretin (1 pmol/kg/min) and placebo (saline), respectively, with an interposed 2-month wash-out period. After 30 min of infusion, a standardized liquid-mixed meal was ingested, and after 5 h, food intake and meal duration were assessed during an ad libitum meal test. Brown adipose tissue activity was assessed regularly by thermal imaging-measured supraclavicular skin temperature.
Compared with placebo, secretin significantly decreased ad libitum food intake by 173 ± 88 kcal (95% CI, 0.76-0.99, P = .039) but did not alter ad libitum meal duration. Secretin acutely decreased BAT activity but increased it postprandially compared with placebo. Acetaminophen-assessed gastric emptying was not affected by exogenous secretin, but secretin increased gallbladder volume, bile acid synthesis, and circulating levels of lipase, amylase, and triglycerides, while decreasing plasma Na+. Compared with placebo, secretin infusion was associated with 24.0 ± 10.8% (95% CI, 0.3-1, P = .025) more adverse events (headache, nausea, diarrhea, and vomiting).
In healthy men, secretin infusion decreased ad libitum food intake concomitantly with a postprandial increase in BAT activity as assessed by thermal imaging-measured supraclavicular skin temperature.
Clinicaltrials.gov, NCT04613700.
激素促胰液素以调节十二指肠pH值而闻名，据推测它在小鼠中具有通过促胰液素诱导的棕色脂肪组织（BAT）激活介导的食欲抑制特性。我们研究了外源性促胰液素对健康男性志愿者随意进食量、BAT活性和餐后生理功能的影响。
在一项随机、安慰剂对照、双盲、交叉研究中，25名健康男性分别接受两次5小时的静脉输注，一次输注促胰液素（1 pmol/kg/分钟），另一次输注安慰剂（生理盐水），中间间隔2个月的洗脱期。输注30分钟后，摄入标准化的液体混合餐，5小时后，在随意进餐试验中评估食物摄入量和进餐持续时间。通过热成像测量锁骨上皮肤温度定期评估棕色脂肪组织活性。
与安慰剂相比，促胰液素使随意进食量显著减少173±88千卡（95%CI，0.76 - 0.99，P = 0.039），但未改变随意进餐持续时间。与安慰剂相比，促胰液素急性降低BAT活性，但餐后使其增加。对乙酰氨基酚评估的胃排空不受外源性促胰液素影响，但促胰液素增加胆囊体积、胆汁酸合成以及脂肪酶、淀粉酶和甘油三酯的循环水平，同时降低血浆钠浓度。与安慰剂相比，输注促胰液素与多24.0±10.8%（95%CI，0.3 - 1，P = 0.025）的不良事件（头痛、恶心、腹泻和呕吐）相关。
在健康男性中，输注促胰液素减少了随意进食量，同时通过热成像测量的锁骨上皮肤温度评估显示餐后BAT活性增加。
Clinicaltrials.gov，NCT04613700。
