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Autophagy and the Peroxisome Proliferator-Activated Receptor Signaling Pathway: A Molecular Ballet in Lipid Metabolism and Homeostasis Publisher

Summary: Review suggests PPARs link autophagy and lipid metabolism, impacting obesity and heart disease treatment strategies. #Metabolism #HealthResearch

Kiani P1 ; Khodadadi ES2 ; Nikdasti A12 ; Yarahmadi S3 ; Gheibi M4 ; Yousefi Z5 ; Ehtiati S6 ; Yahyazadeh S7 ; Shafiee SM8 ; Taghizadeh M9 ; Igder S10 ; Khatami SH6 ; Karima S11 ; Vakili O1 Show All Authors
Authors
  1. Kiani P1
  2. Khodadadi ES2
  3. Nikdasti A12
  4. Yarahmadi S3
  5. Gheibi M4
  6. Yousefi Z5
  7. Ehtiati S6
  8. Yahyazadeh S7
  9. Shafiee SM8
  10. Taghizadeh M9
  11. Igder S10
  12. Khatami SH6
  13. Karima S11
  14. Vakili O1
  15. Pourfarzam M1

Source: Molecular and Cellular Biochemistry Published:2025


Abstract

Lipids, which are indispensable for cellular architecture and energy storage, predominantly consist of triglycerides (TGs), phospholipids, cholesterol, and their derivatives. These hydrophobic entities are housed within dynamic lipid droplets (LDs), which expand and contract in response to nutrient availability. Historically perceived as a cellular waste disposal mechanism, autophagy has now been recognized as a crucial regulator of metabolism. Within this framework, lipophagy, the selective degradation of LDs, plays a fundamental role in maintaining lipid homeostasis. Dysregulated lipid metabolism and autophagy are frequently associated with metabolic disorders such as obesity and atherosclerosis. In this context, peroxisome proliferator-activated receptors (PPARs), particularly PPAR-γ, serve as intracellular lipid sensors and master regulators of gene expression. Their regulatory influence extends to both autophagy and lipid metabolism, indicating a complex interplay between these processes. This review explores the hypothesis that PPARs may directly modulate autophagy within the realm of lipid metabolism, thereby contributing to the pathogenesis of metabolic diseases. By elucidating the underlying molecular mechanisms, we aim to provide a comprehensive understanding of the intricate regulatory network that connects PPARs, autophagy, and lipid homeostasis. The crosstalk between PPARs and other signaling pathways underscores the complexity of their regulatory functions and the potential for therapeutic interventions targeting these pathways. The intricate relationships among PPARs, autophagy, and lipid metabolism represent a pivotal area of research with significant implications for understanding and treating metabolic disorders. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
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