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Oxyntomodulin physiology and its therapeutic development in obesity and associated complications

Martin T W Kueh1,2, Ming Chuen Chong3, Alexander D Miras4

  • 1UCD School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.

The Journal of Physiology
|November 4, 2024
PubMed

Insights

Oxyntomodulin (OXM) offers a dual-receptor activation for obesity treatment, surpassing single incretin effects. This review explores OXM

Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Obesity Research

Background:

  • Incretin-based therapies, including glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), have revolutionized obesity management.
  • Oxyntomodulin (OXM) is a dual-acting hormone that targets both glucagon receptors (GCGR) and GLP1 receptors (GLP1R).

Purpose of the Study:

  • To review the molecular mechanisms and physiological actions of oxyntomodulin (OXM).
  • To discuss the therapeutic potential of OXM-based treatments for obesity and related conditions.
  • To highlight challenges and considerations for the clinical translation of OXM therapies.

Main Methods:

  • Literature review of preclinical and clinical studies on oxyntomodulin.
  • Analysis of molecular signaling pathways activated by OXM.
  • Synthesis of data on OXM's effects on appetite, energy expenditure, and glucose metabolism.

Main Results:

  • OXM exhibits a broader range of physiological effects compared to single incretins due to dual receptor activation.
  • Key actions include significant appetite regulation, increased energy expenditure, and improved glucose homeostasis.
  • Ongoing research focuses on developing stable and effective OXM-based therapeutic agents.

Conclusions:

  • Oxyntomodulin presents a promising therapeutic strategy for obesity, offering multifaceted benefits.
  • Further translational research is crucial to optimize OXM-based therapies for clinical application.
  • OXM's dual-receptor agonism may offer a more comprehensive approach to achieving 'health gains' in obesity care.
Keywords:
energy expenditureglucose metabolismgut‐brain axisobesityoxyntomodulin

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