Ppara, also known as peroxisome proliferator-activated receptor alpha, is a ligand-activated transcription factor that serves as a key mediator of lipid metabolism and metabolic stress in the liver [1]. It is involved in multiple pathways, such as regulating fatty acid transport and catabolism, and is crucial for maintaining lipid homeostasis [2]. Genetic models, especially KO/CKO mouse models, have been valuable in studying its functions.

In Cbfa2t3 -/- mice, insulin resistance increased compared to Cbfa2t3+/+ mice, and lipid droplet and lipid accumulation occurred in the liver during fasting, indicating that hepatic CBFA2T3, a PPARA -sensitive gene, may modulate metabolic stress in mouse liver [1]. Intestine-specific Ppara disruption in mice fed a high-fat diet decreased obesity-associated metabolic disorders and non-alcoholic steatohepatitis (NASH), suggesting that intestinal PPARα signaling promotes NASH progression through regulating dietary fatty acid uptake [2].

In conclusion, Ppara is essential for lipid metabolism and metabolic stress regulation. Studies using KO/CKO mouse models have revealed its significant roles in diseases like insulin resistance-related lipid metabolism disorders and NASH, providing valuable insights into understanding disease mechanisms and potential therapeutic targets.