1.Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice
Songling JIANG ; Md Jamal UDDIN ; Xiaoying YU ; Lingjuan PIAO ; Debra DOROTEA ; Goo Taeg OH ; Hunjoo HA
Diabetes & Metabolism Journal 2022;46(6):829-842
Background:
Non-alcoholic fatty liver disease (NAFLD) has been increasing in association with the epidemic of obesity and diabetes. Peroxisomes are single membrane-enclosed organelles that play a role in the metabolism of lipid and reactive oxygen species. The present study examined the role of peroxisomes in high-fat diet (HFD)-induced NAFLD using fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist.
Methods:
Eight-week-old male C57BL/6J mice were fed either a normal diet or HFD for 12 weeks, and fenofibrate (50 mg/kg/day) was orally administered along with the initiation of HFD.
Results:
HFD-induced liver injury as measured by increased alanine aminotransferase, inflammation, oxidative stress, and lipid accumulation was effectively prevented by fenofibrate. Fenofibrate significantly increased the expression of peroxisomal genes and proteins involved in peroxisomal biogenesis and function. HFD-induced attenuation of peroxisomal fatty acid oxidation was also significantly restored by fenofibrate, demonstrating the functional significance of peroxisomal fatty acid oxidation. In Ppara deficient mice, fenofibrate failed to maintain peroxisomal biogenesis and function in HFD-induced liver injury.
Conclusion
The present data highlight the importance of PPARα-mediated peroxisomal fitness in the protective effect of fenofibrate against NAFLD.
2.The clinical value of dynamic monitoring of serum heparin binding protein, procalcitonin and IL-18 in evaluating the severity of acute pancreatitis
Songling XIE ; Leilei GAN ; Gaosheng WANG ; Li ZHENG ; Zheng JIANG
Chinese Journal of Hepatobiliary Surgery 2021;27(10):767-770
Objective:To investigate the correlations between level of serum heparin binding protein (HBP), procalcitonin (PCT), interleukin-18 (IL-18) and the severity of acute pancreatitis (AP).Methods:A total of 86 patients with AP admitted to the First Affiliated Hospital, University of Science and Technology of China from December 2017 to May 2019 were included and divided into mild AP group (MAP) with 36 cases, moderate AP group (MSAP) with 26 cases, and severe AP group (SAP) with 24 cases. There were 25 healthy subjects were chosen as the control group. Serum HBP, PCT, and IL-18 levels were dynamically monitored in all patients at 1, 3 and 7 days after admission. The Spearman correlation analysis was conducted to detect the correlation between the three indicators and inflammatory factors IL-6, IL-8, TNF-α, and APACHEII and Ranson score, and analyzed the early diagnostic value of HBP, PCT, and IL-18 in SAP patients.Results:In 86 AP patients, 53 were males and 33 were females, aged (48.3±8.0) years. In 25 healthy subjects, 15 were males and 10 were females, aged (40.5±5.9) years. Serum levels of HBP, PCT and IL-18 in AP patients were significantly higher than those of healthy control group at 1, 3 and 7 days after admission ( P<0.05), and the most significant increase was observed on the 1st day. At the meanwhile, HBP, PCT, and IL-18 were positively correlated with level of IL-6, IL-8, TNF-α, APACHEII and Ranson scores ( P<0.05). The AUC area of SAP diagnosis by using HBP, PCT or IL-18 alone was respectively 0.825, 0.896, 0.799, the Yoden index was respectively 0.605, 0.628, 0.583, the sensitivity and specificity were 75.3%, 76.2%, 74.8% and 85.2%, 86.6%, 83.5%. The AUC area, Yoden index, sensitivity and specificity of joint detection were 0.923, 0.787, 85.5%, 93.2%, and the positive predictive value and negative predictive value were also increased. Conclusion:Monitoring of serum HBP, PCT and IL-18 can predict the severity of AP patients, and it may serve as an early diagnostic marker for AP.