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Autophagy in Obesity and Type 2 Diabetes: Beyond the Protective Paradigm

M Elena Angarita-Plánchez1,2, Paula Sánchez-Rodríguez1, Ana M Múnera-Rodríguez1

  • 1Department of Medical Biochemistry, Molecular Biology and Immunology, Faculty of Medicine, University of Seville. Av. Sánchez Pizjuan S/N, 41009, Seville, Spain.

Current Obesity Reports
|May 8, 2026
PubMed
Abstract

Insights

Autophagy dysregulation in obesity and type 2 diabetes mellitus (T2DM) is tissue-specific, not uniformly suppressed. Understanding this context-dependent maladaptation is key for developing precision therapies.

Area of Science:

  • Cellular Biology
  • Metabolic Disease Research

Background:

  • Autophagy plays a crucial role in cellular homeostasis.
  • Dysregulation of autophagy is implicated in various metabolic disorders, including obesity and type 2 diabetes mellitus (T2DM).

Purpose of the Study:

  • To review current evidence on autophagy dysregulation in obesity and T2DM.
  • To emphasize the tissue-specific nature of these autophagic alterations.
  • To explore the implications for clinical translation and therapeutic strategies.

Main Methods:

  • Review of preclinical and human studies on autophagy markers (LC3, p62, Beclin-1) in metabolic diseases.
  • Analysis of signaling pathways involved (mTORC1-AMPK).
  • Examination of recent advances in assessing autophagic flux and biomarkers.

Main Results:

  • Autophagic alterations in metabolic disease are tissue- and stage-dependent, not uniformly suppressed.
  • Dysregulated signaling, mitophagy, and lysosomal function contribute to insulin resistance and metaflammation in key tissues.
  • Current human studies often rely on static markers, limiting reliable assessment of autophagic flux.

Conclusions:

  • Autophagy in metabolic disease is a context-dependent maladaptation.
  • New biomarkers and functional assays are needed for accurate assessment of autophagic flux in humans.
  • Integrating these with metabolic phenotyping is crucial for precision therapeutic strategies.
Keywords:
Autophagy fluxBiomarkersMitophagyObesityTherapeutic targetsType 2 diabetes

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