Exposure to Plasma From Non-alcoholic Fatty Liver Disease Patients Affects Hepatocyte Viability, Generates Mitochondrial Dysfunction, and Modulates Pathways Involved in Fat Accumulation and Inflammation

Frontiers in Medicine

article

Elena Grossini¹  Mario Pirisi²  Divya Praveen Garhwal¹  Giuseppe Calamita³  Raffaele Romito⁴  Cristina Rigamonti¹  Rosalba Minisini¹  Carlo Smirne¹  Daniela Surico¹  Mattia Bellan¹ 

[1] Laboratory of Physiology, Department of Translational Medicine, University East Piedmont;Internal Medicine Unit, Department of Translational Medicine, University East Piedmont;Laboratory of Cellular and Molecular Physiology and Pathophysiology, Department of Biosciences, University of Bari “Aldo Moro”;General Surgery Unit, Azienda Ospedaliera Maggiore della Carità University Hospital;Obstetrics and Gynecology Unit, Department of Translational Medicine, University East Piedmont

关键词: biomarker;    inflammasome;    mitochondria;    NAFLD;    oxidative stress;   

DOI  :  10.3389/fmed.2021.693997

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Changes of lipidic storage, oxidative stress and mitochondrial dysfunction may be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Although the knowledge of intracellular pathways has vastly expanded in recent years, the role and mechanisms of circulating triggering factor(s) are debated. Thus, we tested the hypothesis that factors circulating in the blood of NAFLD patients may influence processes underlying the disease. Huh7.5 cells/primary human hepatocytes were exposed to plasma from 12 NAFLD patients and 12 healthy subjects and specific assays were performed to examine viability, H 2 O 2 and mitochondrial reactive oxygen species (ROS) release, mitochondrial membrane potential and triglycerides content. The involvement of NLRP3 inflammasome and of signaling related to peroxisome-proliferator-activating-ligand-receptor-γ (PPARγ), sterol-regulatory-element-binding-protein-1c (SREBP-1c), nuclear-factor-kappa-light-chain-enhancer of activated B cells (NF-kB), and NADPH oxidase 2 (NOX2) was evaluated by repeating the experiments in the presence of NLRP3 inflammasome blocker, MCC950, and through Western blot. The results obtained shown that plasma of NAFLD patients was able to reduce cell viability and mitochondrial membrane potential by about 48 and 24% ( p < 0.05), and to increase H 2 O 2 , mitochondrial ROS, and triglycerides content by about 42, 19, and 16% ( p < 0.05), respectively. An increased expression of SREBP-1c, PPARγ, NF-kB and NOX2 of about 51, 121, 63, and 46%, respectively, was observed ( p < 0.05), as well. Those effects were reduced by the use of MCC950. Thus, in hepatocytes, exposure to plasma from NAFLD patients induces a NAFLD-like phenotype by interference with NLRP3-inflammasome pathways and the activation of intracellular signaling related to SREBP-1c, PPARγ, NF-kB and NOX2.

【 授权许可】

CC BY