Peroxisome proliferator-activated receptor α (PPARα) plays a critical role in the adaptive response to fasting by regulating hepatic fatty acid oxidation. PPARα-null mice exhibit severe metabolic defects during fasting, including fatty liver, hypoglycemia, hypoketonemia, and elevated plasma free fatty acid levels, indicating impaired fatty acid uptake and oxidation. In contrast, wild-type mice show increased PPARα mRNA expression during fasting, which is essential for maintaining energy homeostasis. PPARα is involved in the transcriptional regulation of genes related to fatty acid metabolism, including those involved in mitochondrial and peroxisomal β-oxidation, fatty acid uptake, and lipoprotein assembly. The study demonstrates that PPARα is crucial for the metabolic adaptation during fasting, as its absence leads to a failure in fatty acid oxidation, resulting in severe metabolic disturbances. PPARα also plays a key role in maintaining body temperature during fasting, as PPARα-null mice are hypothermic and have a lower metabolic rate. The findings highlight the importance of PPARα in the regulation of lipid and carbohydrate metabolism during fasting, and its potential therapeutic relevance in metabolic disorders.Peroxisome proliferator-activated receptor α (PPARα) plays a critical role in the adaptive response to fasting by regulating hepatic fatty acid oxidation. PPARα-null mice exhibit severe metabolic defects during fasting, including fatty liver, hypoglycemia, hypoketonemia, and elevated plasma free fatty acid levels, indicating impaired fatty acid uptake and oxidation. In contrast, wild-type mice show increased PPARα mRNA expression during fasting, which is essential for maintaining energy homeostasis. PPARα is involved in the transcriptional regulation of genes related to fatty acid metabolism, including those involved in mitochondrial and peroxisomal β-oxidation, fatty acid uptake, and lipoprotein assembly. The study demonstrates that PPARα is crucial for the metabolic adaptation during fasting, as its absence leads to a failure in fatty acid oxidation, resulting in severe metabolic disturbances. PPARα also plays a key role in maintaining body temperature during fasting, as PPARα-null mice are hypothermic and have a lower metabolic rate. The findings highlight the importance of PPARα in the regulation of lipid and carbohydrate metabolism during fasting, and its potential therapeutic relevance in metabolic disorders.