The Gut Hormones PYY3-36 and GLP-17-36 amide Reduce Food Intake and Modulate Brain Activity in Appetite Centers in Humans

TLDR

Obesity is a major public health issue, and understanding brain control of appetite—particularly the postprandial corelease of PYY and GLP‑1, which reduce appetite—offers promising therapeutic avenues. The study aims to determine how GLP‑1 and the combined action of PYY and GLP‑1 modulate brain activity in humans, an effect previously unknown. Functional MRI was used in healthy, normal‑weight subjects to assess the effects of PYY(3‑36) and GLP‑1(7‑36 amide) administration and compare them to physiological responses after a meal. Combined PYY(3‑36) and GLP‑1(7‑36 amide) administration in fasted humans reduced subsequent energy intake and brain activity to levels similar to those seen after feeding.

Abstract

Obesity is a major public health issue worldwide. Understanding how the brain controls appetite offers promising inroads toward new therapies for obesity. Peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) are coreleased postprandially and reduce appetite and inhibit food intake when administered to humans. However, the effects of GLP-1 and the ways in which PYY and GLP-1 act together to modulate brain activity in humans are unknown. Here, we have used functional MRI to determine these effects in healthy, normal-weight human subjects and compared them to those seen physiologically following a meal. We provide a demonstration that the combined administration of PYY(3-36) and GLP-1(7-36 amide) to fasted human subjects leads to similar reductions in subsequent energy intake and brain activity, as observed physiologically following feeding.