Clinical Scorecard: Exploring the Neurogenic Mechanism Behind Antiobesity Treatments: A Future Perspective?

At a Glance

Key Highlights

• Prescriptions of antiobesity medications, especially GLP-1R and GIP receptor agonists like semaglutide and tirzepatide, have doubled since 2018.
• AOMs target neurons in the medial basal hypothalamus (MBH), activating anorexigenic POMC+ neurons and inhibiting orexigenic NPY/AgRP neurons.
• AOMs reduce proliferation and increase quiescence of hypothalamic neural stem cells, potentially preserving adult neurogenesis and contributing to neuroprotection and anorexigenic effects.

Guideline-Based Recommendations

Diagnosis

• Identify obesity as the primary indication for antiobesity medication use.

Management

• Use GLP-1 receptor agonists (e.g., liraglutide, semaglutide) and GIP receptor agonists (e.g., tirzepatide) to reduce food intake and body weight.
• Consider the potential neuroprotective and neurogenic effects of AOMs beyond appetite suppression.

Monitoring & Follow-up

• Monitor patient response to AOMs including weight loss and potential cognitive or mood-related benefits.
• Observe for changes in hypothalamic function or neurogenic markers where feasible in research contexts.

Risks

• Be aware that the full neurogenic mechanisms and long-term effects of AOMs on hypothalamic neurogenesis remain under investigation.
• Recognize that AOMs do not alter the proportion of anorexigenic neurons but may affect neuronal connectivity and function.

Patient & Prescribing Data

Adults with obesity, including those consuming high-fat diets

AOMs like liraglutide and lipidized prolactin-releasing peptide analogs reduce hypothalamic neural stem cell proliferation and promote neuronal survival, potentially enhancing treatment efficacy and neuroprotection.

Clinical Best Practices

• Prescribe second- and third-generation peptidic agonists targeting GLP-1R and GIP receptors for obesity management.
• Consider the broader neuroprotective and neurogenic effects of AOMs when evaluating treatment benefits.
• Support further research into hypothalamic adult neurogenesis as a mechanism underlying obesity and its treatment.
• Monitor patients for both metabolic and potential neurocognitive outcomes during AOM therapy.

References

• Doubling of antiobesity medication prescriptions since 2018
• Neuroprotection by GLP-1 receptor agonists
• Activation of POMC+ neurons and inhibition of NPY/AgRP neurons by liraglutide and semaglutide
• Semaglutide transport across blood–brain barrier by tanycytes
• Role of hypothalamic neural stem cells in adult neurogenesis
• Effects of liraglutide and lipidized PrRP analog on hypothalamic neurogenesis
• Review of GLP-1 receptor agonists increasing hippocampal neurogenesis
• Ablation of hypothalamic adult neurogenesis increases weight gain on high-fat diet
• Adult hypothalamic neurogenesis and neuron subtype ratios under high-fat diet
• Neurogenic hypothesis of antidepressant efficacy