Secretin modulates appetite via brown adipose tissue-brain axis

Eur J Nucl Med Mol Imaging. 2023 May;50(6):1597-1606. doi: 10.1007/s00259-023-06124-4. Epub 2023 Feb 11.

Abstract

Purpose: Secretin activates brown adipose tissue (BAT) and induces satiation in both mice and humans. However, the exact brain mechanism of this satiety inducing, secretin-mediated gut-BAT-brain axis is largely unknown.

Methods and results: In this placebo-controlled, single-blinded neuroimaging study, firstly using [18F]-fluorodeoxyglucose (FDG) PET measures (n = 15), we established that secretin modulated brain glucose consumption through the BAT-brain axis. Predominantly, we found that BAT and caudate glucose uptake levels were negatively correlated (r = -0.54, p = 0.037) during secretin but not placebo condition. Then, using functional magnetic resonance imaging (fMRI; n = 14), we found that secretin improved inhibitory control and downregulated the brain response to appetizing food images. Finally, in a PET-fMRI fusion analysis (n = 10), we disclosed the patterned correspondence between caudate glucose uptake and neuroactivity to reward and inhibition, showing that the secretin-induced neurometabolic coupling patterns promoted satiation.

Conclusion: These findings suggest that secretin may modulate the BAT-brain metabolic crosstalk and subsequently the neurometabolic coupling to induce satiation. The study advances our understanding of the secretin signaling in motivated eating behavior and highlights the potential role of secretin in treating eating disorders and obesity.

Trial registration: EudraCT no. 2016-002373-35, registered 2 June 2016; Clinical Trials no. NCT03290846, registered 25 September 2017.

Keywords: Inhibition; Neurometabolic coupling; PET; Satiation; Secretin; fMRI.

Publication types

  • Controlled Clinical Trial
  • Comment

MeSH terms

  • Adipose Tissue, Brown* / drug effects
  • Adipose Tissue, Brown* / metabolism
  • Adipose Tissue, Brown* / physiology
  • Appetite* / drug effects
  • Appetite* / physiology
  • Brain* / drug effects
  • Brain* / metabolism
  • Brain* / physiology
  • Brain-Gut Axis* / drug effects
  • Brain-Gut Axis* / physiology
  • Feeding Behavior* / drug effects
  • Food
  • Functional Neuroimaging*
  • Glucose / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Positron-Emission Tomography
  • Reward
  • Satiety Response* / drug effects
  • Satiety Response* / physiology
  • Secretin* / metabolism
  • Secretin* / pharmacology
  • Signal Transduction / drug effects
  • Single-Blind Method

Substances

  • Secretin
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT03290846