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Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Ppublish 7 citations

PubMed: 34590334 DOI: 10.1111/acer.14719

Effect of intravenous ghrelin administration, combined with alcohol, on circulating metabolome in heavy drinking individuals with alcohol use disorder.

Alcohol Clin Exp Res 45(11):2207-2216

Authors: Olli Kärkkäinen, Mehdi Farokhnia, Anton Klåvus, Seppo Auriola, Marko Lehtonen, Sara L Deschaine, Daria Piacentino, Kelly M Abshire, Shelley N Jackson, Lorenzo Leggio

Affiliations

  • School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
  • Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, Baltimore and Bethesda, Maryland, USA.
  • Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
  • Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
  • Center on Compulsive Behaviors, National Institutes of Health, Bethesda, Maryland, USA.
  • Translational Analytical Core, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA.
  • Medication Development Program, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
  • Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, Rhode Island, USA.
  • Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
  • Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA.

Abstract

BACKGROUND

Ghrelin may influence several alcohol-related behaviors in animals and humans by modulating central and/or peripheral biological pathways. The aim of this exploratory analysis was to investigate associations between ghrelin administration and the human circulating metabolome during alcohol exposure in nontreatment seeking, heavy drinking individuals with alcohol use disorder (AUD).

METHODS

We used serum samples from a randomized, crossover, double-blind, placebo-controlled human laboratory study with intravenous (IV) ghrelin or placebo infusion in two experiments. During each session, participants received a loading dose (3 µg/kg) followed by continuous infusion (16.9 ng/kg/min) of acyl ghrelin or placebo. The first experiment included an IV alcohol self-administration (IV-ASA) session and the second experiment included an IV alcohol clamp (IV-AC) session, both with the counterbalanced infusion of ghrelin or placebo. Serum metabolite profiles were analyzed from repeated blood samples collected during each session.

RESULTS

In both experiments, ghrelin infusion was associated with an altered serum metabolite profile, including significantly increased levels of cortisol (IV-ASA q-value = 0.0003 and IV-AC q < 0.0001), corticosterone (IV-ASA q = 0.0202 and IV-AC q < 0.0001), and glycochenodeoxycholic acid (IV-ASA q = 0.0375 and IV-AC q = 0.0013). In the IV-ASA experiment, ghrelin infusion increased levels of cortisone (q = 0.0352) and fatty acids 18:1 (q = 0.0406) and 18:3 (q = 0.0320). Moreover, in the IV-AC experiment, ghrelin infusion significantly increased levels of glycocholic acid (q < 0.0001) and phenylalanine (q = 0.0458).

CONCLUSION

IV ghrelin infusion, combined with IV alcohol administration, was associated with increases in the circulating metabolite levels of corticosteroids and glycine-conjugated bile acids, among other changes. Further research is needed to understand the role that metabolomic changes play in the complex interaction between ghrelin and alcohol.

MeSH

Serum, Alcoholism, Adrenal Cortex Hormones, Metabolomics, Drinking, Ghrelin

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