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

Abstract

SummaryObesity 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 PYY3-36 and GLP-17-36 amide to fasted human subjects leads to similar reductions in subsequent energy intake and brain activity, as observed physiologically following feeding.

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

“…Both PYY and GLP-1 act upon brain homeostatic and reward circuits to modulate feeding behavior (70)(71)(72)(73); thus, enhancement of their secretion is a plausible mechanism for the effects of RYGBP on energy intake. Robust evidence from experimental imaging and translational studies indicate that the biologically active form of PYY, PYY3-36, mediates its anorectic effects predominantly by acting upon central appetite-regulating circuits, the hypothalamic arcuate nucleus and brain regions involved in food reward having been identified as key areas (73).…”

Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS

“…The effects of GLP-1 infusion on fMRI-measured neuronal activity have also been studied in humans (DeSilva et al 2011). In healthy normal-weight individuals (11 males and five females), the mean fMRI signal change was described in a priori selected brain regions involved in reward processing and hedonic feeding (dorsal striatum, NAc, insula, amygdala and orbitofrontal cortex).…”

Glucagon-Like Peptide-1 Analogues and Anxiety and Abnormal Eating Behaviours in Type 2 Diabetes: A Case Report

“…Given the evidence from animal studies of GLP-1-induced reduction in alcohol intake and in the modulation of the locomotor response precipitated by amphetamine indicates that the reward centres (mesolimbic pathway) may have a role in this effect [6,7]. Further evidence of central action of exenatide in fMRI studies [13], supports this: although the exact mechanism whereby GLP-1 mediates an effect on anxiety remains unclear, it is likely to be associated with receptors in the mesolimbic system.…”

“…There is evidence of central action of exenatide in fMRI studies [13], and some early neuro-physiology studies have examined the role of GLP-1 in the biomechanisms behind eating disorders, finding a correlation between impaired post-prandial secretion of GLP-1 and active bingeing-vomiting behaviours in bulaemia nervosa [14].…”