Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms

Abstract

Objectives: Intragastric bitter tastants may decrease appetite and food intake. We aimed to investigate the gut-brain signaling and brain mechanisms underlying these effects.

Methods: Brain responses to intragastric quinine-hydrochloride (QHCl, 10 µmol/kg) or placebo infusion were recorded using functional magnetic resonance imaging in 15 healthy women. Appetite-related sensations, plasma levels of gastrointestinal hormones and hedonic food intake (ad libitum drink test) were assessed.

Results: Lower octanoylated ghrelin (P<0.04), total ghrelin (P<0.01), and motilin (P<0.01) plasma levels were found after QHCl administration, along with lower prospective food consumption ratings (P<0.02) and hedonic food intake (P<0.05). QHCl increased neural activity in the hypothalamus and hedonic (anterior insula, putamen, caudate, pallidum, amygdala, anterior cingulate cortex, orbitofrontal cortex, midbrain) regions, but decreased activity in the homeostatic medulla (all pFWE-corrected<0.05). Differential brain responses to QHCl versus placebo covaried with subjective and hormonal responses and predicted differences in hedonic food intake.

Discussion: Intragastric QHCl decreases prospective and actual food intake in healthy women by interfering with homeostatic and hedonic brain circuits in a ghrelin- and motilin-mediated fashion. These findings suggest a potential of bitter tastants to reduce appetite and food intake, through the gut-brain axis.

Keywords:

• Bitter tastants
• Quinine
• Appetite
• Pharmacological MRI
• Brain-gut axis
• Ghrelin
• Motilin
• Food intake

Acknowledgments

We would like to acknowledge the infrastructural support of the Magnetic Resonance Imaging Unit, Radiology Division, University Hospital Gasthuisberg. We would also like to thank Dr Huynh Giao Ly, Nathalie Weltens, Ronald Peeters, and Joran Tóth for their technical help and assistance with laboratory analyses.

Disclaimer statement

Contributors None.

Funding This work was supported by the Research Foundation – Flanders (Fonds Wetenschappelijk Onderzoek, FWO-Vlaanderen) awarded to Prof. Lukas Van Oudenhove and Prof. Inge Depoortere under Grant G073615.

Conflict of interest None.

Ethics approval None.

ORCID

Eveline Deloose http://orcid.org/0000-0001-8694-7745

Inge Depoortere http://orcid.org/0000-0002-0289-2175

Jan Tack http://orcid.org/0000-0002-3206-6704

Lukas Van Oudenhove http://orcid.org/0000-0002-6540-3113