1224-P: Exogenous Secretin Decreases Energy Intake and Exerts a Bimodular Effect on Postprandial Brown Adipose Tissue Activation in Man

Abstract

Secretin was recently shown to constitute a postprandial satiety signal in mice. This effect was proposed to be mediated by secretin-induced activation of brown adipose tissue (BAT) and subsequent hypothalamic registration of body temperature rise. We investigated the effect of a 5-hour infusion of secretin on appetite sensations, food intake, BAT activity and resting energy expenditure (REE) in man. In a randomized, double-blind, placebo-controlled, crossover study, 25 healthy males aged (mean ± SD) 25.7 ± 6.1 years with a BMI of 23.4 ± 1.8 kg/m2 underwent 5-hour infusions of secretin (1 pmol/kg/min) and placebo, respectively, on separate days with an interposed 8-week washout period. During the infusions, before and several times after a liquid mixed meal test, we assessed appetite sensations (by visual analogue scales), REE (by indirect calorimetry) and supraclavicular BAT activity (by thermal imaging). Before terminating the infusions, ad libitum food intake (primary outcome) was assessed. Compared to placebo, secretin did not affect appetite sensations, but it decreased ad libitum food intake by [mean±SEM] 173 ± 88 kcal (P = 0.039). Within the first 15 minutes of infusion, secretin decreased supraclavicular temperature by 0.10 ± 0.02°C (P <0.001), but at 75-90 min and 240-255 min it increased supraclavicular temperature by 0.05 ± 0.01 (P <0.001) and 0.01 ± 0.01 (P <0.001), respectively, compared to placebo. Secretin did not affect REE. During secretin and placebo infusions, 4 and 2 reported headache, 4 and 1 experienced nausea, 2 and 0 participants vomited, and 2 and 0 had diarrhea, respectively. In conclusion, a 5-hour infusion of secretin in healthy males decreased ad libitum food intake and exhibited a biphasic effect of supraclavicular BAT activity. Disclosure S. M. Nguyen heimbürger: Speaker’s Bureau; Self; AstraZeneca. M. J. Bentzen: None. B. Hartmann: None. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. M. B. Christensen: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S.