Dietary alpha-lipoic acid alleviates heat stress by modulating insulin-like signaling to maintain homeostasis <i>in C. elegans</i>

Prolonged exposure to high temperatures can cause oxidative stress in the body, negatively impacting human health. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant prevalent in both plant and animal foods, exhibiting bioactivity comparable to that of vitamins. Although its roles in antioxidant defense and metabolic regulation have been extensively studied, its potential to mitigate heat stress in organisms is less explored and deserves further study. Our research demonstrates that ALA significantly improves the survival rates of <i>Caenorhabditis elegans</i> under heat stress. ALA achieves this by activating heat shock factor 1 (HSF-1) and promoting mitochondrial fission and mitophagy through the transcription factor HLH-30. These processes help alleviate oxidative damage from heat stress, maintain mitochondrial function, and stabilize cellular energy metabolism. Furthermore, the activation of HSF-1 and enhanced mitophagy by dietary ALA depend on the insulin-like signaling peptide 19 (INS-19), suggesting that ALA may target the insulin-like signaling pathway to combat heat stress and maintain homeostasis. These findings indicate that ALA could serve as a valuable dietary supplement for enhancing heat stress resistance in organisms and may inspire the development of novel food ingredients with protective properties against thermal challenges.