The therapeutic potential of GLP-1 analogues for stress-related eating and role of GLP-1 in stress, emotion and mood: a review

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Aug 30:110:110303. doi: 10.1016/j.pnpbp.2021.110303. Epub 2021 Mar 16.

Abstract

Stress and low mood are powerful triggers for compulsive overeating, a maladaptive form of eating leading to negative physical and mental health consequences. Stress-vulnerable individuals, such as people with obesity, are particularly prone to overconsumption of high energy foods and may use it as a coping mechanism for general life stressors. Recent advances in the treatment of obesity and related co-morbidities have focused on the therapeutic potential of anorexigenic gut hormones, such as glucagon-like peptide 1 (GLP-1), which acts both peripherally and centrally to reduce energy intake. Besides its appetite suppressing effect, GLP-1 acts on areas of the brain involved in stress response and emotion regulation. However, the role of GLP-1 in emotion and stress regulation, and whether it is a viable treatment for stress-induced compulsive overeating, has yet to be established. A thorough review of the pre-clinical literature measuring markers of stress, anxiety and mood after GLP-1 exposure points to potential divergent effects based on temporality. Specifically, acute GLP-1 injection consistently stimulates the physiological stress response in rodents whereas long-term exposure indicates anxiolytic and anti-depressive benefits. However, the limited clinical evidence is not as clear cut. While prolonged GLP-1 analogue treatment in people with type 2 diabetes improved measures of mood and general psychological wellbeing, the mechanisms underlying this may be confounded by associated weight loss and improved blood glucose control. There is a paucity of longitudinal clinical literature on mechanistic pathways by which stress influences eating behavior and how centrally-acting gut hormones such as GLP-1, can modify these. (250).

Keywords: Addiction; Emotion; GLP-1; Mood; Obesity; Stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Affect / drug effects*
  • Affect / physiology
  • Animals
  • Anti-Obesity Agents / administration & dosage
  • Brain-Gut Axis / drug effects
  • Brain-Gut Axis / physiology
  • Clinical Trials, Phase III as Topic / methods
  • Emotions / drug effects*
  • Emotions / physiology
  • Exenatide / administration & dosage
  • Glucagon-Like Peptide 1 / administration & dosage*
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Humans
  • Hyperphagia / drug therapy*
  • Hyperphagia / metabolism
  • Hyperphagia / psychology
  • Obesity / drug therapy
  • Obesity / metabolism
  • Obesity / psychology
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / metabolism
  • Stress, Psychological / psychology

Substances

  • Anti-Obesity Agents
  • Glucagon-Like Peptide 1
  • Exenatide