Autolysosomal Dysfunction in Obesity-induced Metabolic Inflammation and Related Disorders

Area of Science:

• Cell Biology
• Metabolic Diseases
• Pathophysiology

Background:

• Obesity is a global health crisis linked to metabolic disorders like type 2 diabetes (T2D), MAFLD, and cardiovascular diseases.
• Meta-inflammation, a chronic inflammatory state driven by excess adipose tissue, disrupts metabolic homeostasis in obesity.
• Autolysosomal dysfunction is increasingly recognized as a key factor in obesity's pathophysiology.

Purpose of the Study:

• To review the role of autolysosomal dysfunction in obesity-related metabolic disorders.
• To explore the impact of this dysfunction across multiple metabolic organs.
• To evaluate therapeutic strategies targeting autophagy and lysosomal function.

Main Methods:

• Review of emerging research on autophagy and lysosomal function in obesity.
• Analysis of studies identifying autophagic defects in various metabolic tissues.
• Examination of preclinical data on interventions targeting autolysosomal pathways.

Main Results:

• Obesity-induced lysosomal dysfunction impairs autophagy, leading to cellular damage and exacerbating insulin resistance and inflammation.
• Autophagic defects are found in adipose tissue, liver, muscle, kidney, heart, pancreas, and brain, linking dysregulation to disease progression.
• Preclinical studies demonstrate that interventions like AMPK activation and caloric restriction mimetics can restore autophagic function and improve metabolic outcomes.

Conclusions:

• Autolysosomal dysfunction significantly contributes to obesity-associated metabolic disorders and systemic inflammation.
• Restoring autophagy and lysosomal function presents a promising therapeutic avenue for mitigating obesity-driven pathologies.
• Further research is needed to translate these findings into effective clinical applications for metabolic health.