Autophagy as a key treatment target in metabolic diseases and obesity-related diabetes

Impairment of autophagy is associated with obesity and type 2 diabetes through disruptions in nutrient sensing and stress adaptation.

• Autophagy plays a crucial role in maintaining metabolic health by regulating nutrient sensing and organelle quality control.
• Hyperactivation of MTORC1, coupled with insufficient AMPK and SIRT1 signaling, may suppress autophagy and lead to lipid accumulation and insulin resistance.
• Consequences of impaired autophagy include inflammation and hypertrophy in adipose tissue, liver fat accumulation, pancreatic β-cell dysfunction, and skeletal muscle atrophy.
• Defective autophagy across the gut-liver-brain axis could worsen intestinal barrier function and systemic metabolic health.
• Interventions that aim to restore autophagic capacity, such as exercise and dietary changes, show promise in preliminary studies.
• The complex duality of autophagy's effects in different tissues complicates the development of targeted therapies for metabolic diseases.

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