Dietary adaptation for weight loss maintenance at Yale (DAWLY): Protocol and predictions for a randomized controlled trial

Xi Fang, Xue Davis, Kyle D. Flack, Chavonn Duncan, Fangyong Li, Marney White, Carlos Grilo, Dana M. Small

Research output: Contribution to journalArticlepeer-review


Background: Current therapies for obesity treatment are effective at producing short-term weight loss, but weight loss maintenance remains a significant challenge. Here we investigate the impact of pre-intervention dietary fat intake on the efficacy of a dietary supplement to support weight loss maintenance. Preclinical work demonstrates that a vagal afferent pathway critical for sensing dietary lipids is blunted by a high-fat diet (HFD), resulting in a reduced preference for a low-fat emulsion and severe blunting of the dopamine (DA) response to the gastric infusion of lipids. Infusion of the gut lipid messenger oleoylethanolamide (OEA), which is also depleted by HFD, immediately reverses this DA blunting and restores preference for the low-fat emulsion. Studies of OEA supplementation for weight loss in humans have had limited success. Given the strong effect of HFD on this pathway, we designed a study to test whether the efficacy of OEA as a weight loss treatment is related to pre-intervention habitual intake of dietary fat. Methods/Design: We employed a randomized, double-blind, placebo-controlled trial in which 100 adults with overweight/obesity (OW/OB) were randomized to receive either OEA or placebo daily for 16 months. Following a baseline evaluation of diet, metabolic health, adiposity, and brain response to a palatable an energy dense food, participants in both groups underwent a 4-month behavioral weight loss intervention (LEARN®) followed by a 1-year maintenance period. The study aims are to (1) determine if pre-intervention dietary fat intake moderates the ability of OEA to improve weight loss and weight loss maintenance after a gold standard behavioral weight loss treatment; (2) identify biomarkers that predict outcome and optimize a stratification strategy; and (3) test a model underlying OEA’s effectiveness. Discussion: Focusing on interventions that target the gut-brain axis is supported by mounting evidence for the role of gut-brain signaling in food choice and the modulation of this circuit by diet. If successful, this work will provide support for targeting the gut-brain pathway for weight loss maintenance using a precision medicine approach that is easy and inexpensive to implement. Clinical Trial Registration: [], identifier [NCT04614233].

Original languageEnglish
Article number940064
JournalFrontiers in Nutrition
StatePublished - Jul 28 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Fang, Davis, Flack, Duncan, Li, White, Grilo and Small.


  • Riduzone
  • dietary intake
  • obesity
  • oleoylethanolamide
  • overweight
  • randomized controlled trial
  • supplementation
  • weight loss

ASJC Scopus subject areas

  • Food Science
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics


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