Kiani Pouria, Khodadadi Elaheh Sadat, Nikdasti Ali, Yarahmadi Sahar, Gheibi Mobina, Yousefi Zeynab, Ehtiati Sajad, Yahyazadeh Sheida, Shafiee Sayed Mohammad, Taghizadeh Motahareh, Igder Somayeh, Khatami Seyyed Hossein, Karima Saeed, Vakili Omid, Pourfarzam Morteza
Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122, Padova, Italy.
Mol Cell Biochem. 2025 Jun;480(6):3477-3499. doi: 10.1007/s11010-025-05207-0. Epub 2025 Feb 1.
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.
脂质对于细胞结构和能量储存不可或缺，主要由甘油三酯（TGs）、磷脂、胆固醇及其衍生物组成。这些疏水性物质存在于动态的脂滴（LDs）中，脂滴会根据营养物质的可利用性而扩张和收缩。自噬在历史上被视为一种细胞废物处理机制，现在已被公认为是新陈代谢的关键调节因子。在此框架内，脂噬，即脂滴的选择性降解，在维持脂质稳态中发挥着重要作用。脂质代谢和自噬失调常与肥胖和动脉粥样硬化等代谢紊乱相关。在这种情况下，过氧化物酶体增殖物激活受体（PPARs），尤其是PPAR-γ，充当细胞内脂质传感器和基因表达的主要调节因子。它们的调节影响延伸至自噬和脂质代谢，表明这些过程之间存在复杂的相互作用。本综述探讨了PPARs可能在脂质代谢领域直接调节自噬，从而导致代谢疾病发病机制的假说。通过阐明潜在的分子机制，我们旨在全面了解连接PPARs、自噬和脂质稳态的复杂调节网络。PPARs与其他信号通路之间的相互作用突显了其调节功能的复杂性以及针对这些通路进行治疗干预的潜力。PPARs、自噬和脂质代谢之间的复杂关系代表了一个关键的研究领域。
