LBP Protects Hepatocyte Mitochondrial Function via the PPAR-CYP4a2 Signaling Pathway in a Rat Sepsis Model.

Abstract

OBJECTIVES\nTo explore the role of LBP in metabolism and optimize sepsis treatment.\n\n\nDESIGN\nA sepsis model was established by injecting LPS into LBP-/- rats and WT rats and observing changes in the liver over time (0\u200ah, 1\u200ah, 6\u200ah, and 24\u200ah).\n\n\nSETTING\nDetecting liver inflammation and injury. Optimizing the treatment of sepsis.\n\n\nSUBJECTS\nWT rats and LBP-/- rats.\n\n\nINTERVENTIONS\nWe established a sepsis model by injecting LPS intravenously.\n\n\nMEASUREMENTS AND MAIN RESULTS\nFirst, we induced sepsis in WT and LBP-/- rats with LPS. The rats were sacrificed, and serum and liver samples were collected at 1\u200ah, 6\u200ah and 24\u200ah after LPS injection. We found that the deletion of LBP reduced LPS-induced liver inflammation and injury at 1\u200ah and 6\u200ah. Ballooning degeneration was clearly present in LBP-/- rat livers at 24\u200ah after LPS injection. We found that mitochondrial damage and ROS levels were higher in LBP-/- rat livers than in WT rat livers at 24\u200ah after LPS injection. According to the transcriptomic results, the PPAR pathway may be the reason for lesions in LBP-/- rats. To further investigate the function of PPARα in sepsis, we inhibited mTOR with rapamycin and examined mitochondrial injury and ROS levels. The levels of mitochondrial damage and ROS were reduced after LBP-/- rats were pretreated with rapamycin in the context of LPS-induced sepsis. Inhibiting CYP4a2, one of the PPARα-target gene products, reduced the level of LPS-induced ROS in LBP-/- rats.\n\n\nCONCLUSION\nLBP protects hepatic mitochondria against LPS-induced damage via the LBP-PPARα-CYP4a2 signaling pathway.