Why the study?
Although inflammation contributes to NAFLD pathogenesis, the specific cytokines involved and how they influence liver transformation remain poorly characterized, highlighting the need for new therapeutic molecular targets.
Does IL32 expression correlate with NAFLD severity and induce insulin resistance in human hepatocytes?
Does IL32 expression correlate with NAFLD severity and induce insulin resistance in human hepatocytes?
IL32 is significantly upregulated in NAFLD, correlates with disease severity, and directly induces insulin resistance in hepatocytes, highlighting it as a potential therapeutic target.
Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder due to increased accumulation of fat in the liver and in many cases to enhanced inflammation. Although the contribution of inflammation in the pathogenesis of NAFLD is well established, the cytokines that are involved and how they influence liver transformation are still poorly characterized. In addition, with other modifiers, inflammation influences NAFLD progression to liver cirrhosis and hepatocellular carcinoma, demonstrating the need to find new molecular targets with potential future therapeutic applications. We investigated gene signatures in 38 liver biopsies from patients with NAFLD and obesity who had received bariatric surgery and compared these to 10 control patients who had received a cholecystectomy, using DNA microarray technology. A subset of differentially expressed genes was then validated on a larger cohort of 103 patients who had received bariatric surgery for obesity; data were thoroughly analyzed in terms of correlations with NAFLD pathophysiological parameters. Finally, the impact of a specific cytokine, interleukin‐32 (IL32), was addressed on primary human hepatocytes (PHHs). Transcript analysis revealed an up‐regulation of proinflammatory cytokines IL32, chemokine (C‐X‐C motif) ligand 9 (CXCL9), and CXCL10 and of ubiquitin D (UBD), whereas down‐regulation of insulin‐like growth factor‐binding protein 2 (IGFBP2) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) was reported in patients with NAFLD. Moreover, IL32, which is the major deregulated gene, correlated with body mass index (BMI), waist circumference, NAFLD activity score (NAS), aminotransferases (alanine aminotransferase [ALAT] and aspartate aminotransferase [ASAT]), and homeostasis model assessment of insulin resistance (HOMA‐IR) index in patients. Consistent with an instrumental role in the pathophysiology of NAFLD, treatment of control human hepatocytes with recombinant IL32 leads to insulin resistance, a hallmark metabolic deregulation in NAFLD hepatocytes. Conclusion: IL32 has a critical role in the pathogenesis of NAFLD and could be considered as a therapeutic target in patients.
No takes yet. Share an insight, caveat, or question.
Dali‐Youcef et al. (2019) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: