Secretin Activates Human Brown Fat and Induces Satiation.

Obesity

15 healthy males will be studied with PET/CT, using FDG to investigate glucose metabolism, and radiowater to investigate perfusion. One scan will be performed in controlled cold exposure, to see whether subjects have cold activated brown adipose tissue. Two scans will be performed in room temperature conditions, where all subjects are blinded and randomised to receive placebo and secretin hydrochloride. PET/CT scans will be analysed blinded. 20 healthy males will also be studied with fMRI, in order to investigate brain activity responses to appetizing versus bland foods. This study will be conduced on the same patients as the PET/CT study, but additional subjects with same inclusion and exclusion criteria will be recruited. Two fMRI scans will be performed in room temperature conditions, where all subjects are blinded and randomised to receive placebo and secretin hydrochloride. fMRI scans will be analysed blinded.

The PET/CT study will consist of 15 healthy, normal weight males, between ages 18-65. A 2-hour oral glucose tolerance test is performed on screening day. Calorimetry data is collected at baseline (resting and fasting) condition. Three PET/CT scans on three different days will be performed to all 15 study subjects. Radiowater (15O)-H2O is used to study perfusion and FDG ((F18)-FDG) to study glucose metabolism. After radiowater, PET data is collected from the neck area for 6 minutes. After FDG, PET data is collected for 40 minutes on the neck area, 15 minutes on the chest, 15 minutes on the abdomen and 15 minutes on the brain. Calorimetry is collected during the entire scan. Blood samples are collected during scans for metabolites and for a plasma activity curve. One scan is performed during controlled, cold exposure. This is done to investigate, whether patients have cold activated brown adipose tissue. After this, subjects will undergo two room temperature condition scans on different days, where participants are single-blinded and randomised to receive placebo (saline) or secretin (secretin hydrochloride) infusions. All scans are done in fasting conditions. After subjects have fed at the PET centre, calorimetry data is collected on all days. A full body MRI will be performed on a separate day with the Dixon-method. After scanning visits, brown adipose tissue biopsies will be taken from volunteers by a plastic surgeon. These samples are analysed in Munich. Dynamic scan data is analysed with the Carimas program, using Patlak plot. Analysis is performed blinded. Further statistics analysis is done with SPSS. The fMRI study will consist of 20 healthy, normal weight males, between ages 18-65. Subjects who underwent PET/CT scanning will be recruited for this study, as well as an additional group of subjects with the same inclusion and exclusion criteria. A 2-hour oral glucose tolerance test is performed on screening day for additional subjcts. Two fMRI scans are conducted in room temperature after overnight fast on separate days. Subjects are randomized and blinded to receive placebo and secretin hydrochloride on separate days. Data on brain activity while viewing appetizing versus bland food images is collected during scan. After scanning subjects are given a meal and then followed up for two hours. Data on subjective satiety will be collected with a visual analogue scale questionnaire on nine different timepoints during the day: in preprandial, prandial and postprandial conditions. Functional MRI data is analyzed with Matlab. Analysis is performed blinded. Satiety score is analzed with SPSS.

Finland