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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Purpose of review This review examines the current evidence on autophagy dysregulation in obesity and type 2 diabetes mellitus (T2DM), with particular emphasis on its tissue-specific nature and implications for clinical translation. Recent findings Recent human and preclinical evidence indicates that autophagic alterations in metabolic disease are not uniformly suppressed but vary according to tissue type and disease stage. In adipose tissue, liver, skeletal muscle, pancreatic β cells, and immune cells, dysregulated mTORC1-AMPK signaling, defective mitophagy, and impaired lysosomal function contribute to insulin resistance, ectopic lipid accumulation, and metaflammation. However, most human studies rely on static markers such as LC3, p62, and Beclin-1, which do not reliably reflect dynamic autophagic flux. Recent advances, including organelle-specific biomarkers, ex vivo functional assays, and circulating exosomal cargo, offer new translational opportunities, although standardization remains limited. Autophagy in metabolic disease represents a context-dependent maladaptation rather than a uniformly protective pathway. Future progress will depend on harmonized biomarker panels, functional assessment of autophagic flux in humans, and integration with metabolic phenotyping to enable precision-based therapeutic strategies.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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