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Updated: Jan 15, 2026

Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
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Mitochondrial and psychosocial stress-related regulation of FGF21 in humans

Mangesh Kurade1, Natalia Bobba-Alves1, Catherine Kelly1

  • 1Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA.

Nature Metabolism
|October 14, 2025
PubMed

Insights

Psychosocial stress impacts Fibroblast Growth Factor 21 (FGF21) differently in healthy individuals and those with mitochondrial diseases (MitoD). FGF21 may act as a stress hormone, aiding energy demands during stress.

Area of Science:

  • Endocrinology
  • Metabolic Research
  • Neuroscience

Background:

  • Fibroblast Growth Factor 21 (FGF21) is a metabolic hormone.
  • FGF21 levels increase with fasting, metabolic stress, and mitochondrial oxidative phosphorylation (OxPhos) defects causing mitochondrial diseases (MitoD).

Purpose of the Study:

  • To investigate the role of FGF21 in response to acute psychosocial stress.
  • To explore the interaction between FGF21, stress response, and mitochondrial function.

Main Methods:

  • Measured serum FGF21 levels in healthy controls and individuals with MitoD following acute psychosocial stress.
  • Analyzed co-activation patterns of FGF21 with stress-related neuroendocrine hormones.
  • Assessed associations between FGF21 and psychosocial factors.

Main Results:

  • Acute psychosocial stress decreased serum FGF21 by 20% in healthy controls (P < 0.0001).
  • Acute psychosocial stress increased serum FGF21 by 32% in individuals with MitoD (P < 0.0001).
  • Identified co-activation patterns between FGF21 and stress hormones, and links to stress and wellbeing.

Conclusions:

  • FGF21 exhibits differential responses to psychosocial stress based on mitochondrial capacity.
  • FGF21 may function as a stress hormone, supporting energy requirements during psychosocial stress.
  • Highlights a potential link between metabolic health, stress response, and mitochondrial function.

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