Autophagy as a therapeutic linchpin in metabolic Diseases and obesity-associated diabetes - PubMed
4 hours ago
- #Autophagy
- #Metabolic Diseases
- #Obesity
- Autophagy is a conserved lysosomal degradation pathway crucial for metabolic health.
- Impairment of autophagy contributes to obesity and type 2 diabetes by disrupting nutrient sensing, stress adaptation, and organelle quality control.
- Hyperactivation of MTORC1 and insufficient AMPK and SIRT1 signaling suppress autophagic flux, leading to lipid accumulation, insulin resistance, and mitochondrial dysfunction.
- Clinical consequences include adipose inflammation, hepatic steatosis, pancreatic β-cell failure, and skeletal muscle atrophy.
- Defective autophagy across the gut-liver-brain axis exacerbates intestinal barrier dysfunction, endotoxemia, and neuroendocrine imbalance.
- Emerging interventions like exercise, dietary modulation, pharmacological inducers, and nanotechnology-based lysosomal re-acidification show promise in preclinical models.
- The tissue-specific duality of autophagy complicates therapeutic targeting, as suppression may be beneficial in some contexts but harmful in others.
- This review positions autophagy as a therapeutic linchpin in obesity-associated metabolic disease, highlighting opportunities for precision strategies.