ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 25 OC4.7

Co-administration of the gut hormones PYY and GLP-1 to human volunteers reduces food intake and brain activation in appetite centres

Akila De Silva1, Victoria Salem1, Christopher J Long2, Aidan Makwana2, Rexford D Newbould2, Eugenii A Rabiner2, Aniket N Tavare1, Mohammed A Ghatei1, Stephen R Bloom1, Paul M Matthews2, John D Beaver2 & Waljit S Dhillo1

1Imperial College, London, UK; 2GlaxoSmithKline Clinical Imaging Centre, London, UK.

The physiological post-prandial release of the gut hormones PYY and GLP-1 is implicated in triggering CNS mechanisms underlying satiety. However, the combined effects of PYY and GLP-1 on brain circuits underlying satiety in humans remain unknown.

Objective: To determine changes in CNS neuronal activity following single and combined infusions of PYY and GLP-1, using blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) in human volunteers.

Methods: Ten normal weight adult volunteers underwent 5 treatment visits in a randomized, cross-over design. On each visit each subject received a 90 min intravenous infusion of one of the following:

  • i) Saline following an 730 kcal breakfast
  • ii) Saline following an overnight fast
  • iii) GLP-1 0.8 pmol/kg per minute following an overnight fast
  • iv) PYY 0.3 pmol/kg per minute following an overnight fast
  • v) Combined GLP-1 and PYY following an overnight fast

Twenty minutes following the start of each infusion, fMRI data were acquired while participants viewed images of appetising and bland foods. An ad libitum buffet lunch was served to estimate caloric intake following the completion of each infusion.

Results: Gut hormone infusion reduced caloric intake in the fasted state compared to saline infusion (15, 7 and 21% reductions for GLP-1, PYY and GLP-1+PYY respectively). On the fasted saline visit, appetising food images evoked greater BOLD signal relative to bland foods, in the putamen and insula. Single administration of GLP-1 or PYY alone attenuated the difference in BOLD response between appetising and bland foods in the fasted state. This was comparable with that observed in fed subjects receiving saline. Greater attenuation was observed in fasted subjects receiving co-administration of GLP-1 and PYY (P<0.05 cf saline).

Conclusions: These data show for the first time in humans, that changes in CNS neuronal activity following co-administration of GLP-1 and PYY are similar to those observed physiologically after a meal.