Research advancements on dietary bioactive compounds ameliorating lipid deposition mechanisms via autophagy...

The core pathological basis of obesity and its associated metabolic diseases is excessive lipid deposition. Bioactive compounds from dietary resources, such as polyphenols and flavonoids, can significantly improve lipid homeostatic imbalance by activating autophagy pathways, especially lipophagy. This review gives a systematic analysis of the interaction mechanism between autophagy processes and lipid metabolism, focusing on the elucidation of Rab GTPase-mediated membrane transport, membrane proteins involved in lipid droplet recognition and encapsulation, as well as lipid metabolism enzymes facilitating autophagy-dependent lipid clearance. We further illustrate how dietary bioactive compounds modulate the autophagy network via multiple targets, such as the activation of AMPK or inhibition of mTOR to improve autophagy, the promotion of TFEB nuclear translocation to drive lysosomal production, and the enhancement of SIRT1 to coordinate metabolic stress response. Despite the encouraging lipid-lowering effects of these compounds, there are still challenges related to their pleiotropic targets, discrepancies between in vivo and ex vivo studies, limited bioavailability, and long-term safety. Multidisciplinary approaches should be incorporated into future research to facilitate clinical translation, structure-activity relationship analyses, and evaluations of synergistic effects. This review offers insights for developing autophagy-modulating natural dietary agents as interventions against obesity.