IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids.

Cell Rep Med

Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden; Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address:

Published: January 2024

AI Article Synopsis

  • Steatotic liver disease (SLD) is the most common chronic liver condition, but there's no approved treatment due to unclear causes.
  • Elevated levels of interleukin 32 (IL-32) are linked to severe SLD, with research showing that IL-32β increases fat synthesis in liver cells while reducing it when IL32 is decreased.
  • A genetic variant (rs76580947) of IL32 is associated with lower IL-32 levels and may offer protection against SLD, indicating that reducing IL32 could be a potential therapeutic approach.

Article Abstract

Steatotic liver disease (SLD) prevails as the most common chronic liver disease yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, the mechanistic link between IL-32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate in vitro that incubation with IL-32β protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di-lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL-32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829727PMC
http://dx.doi.org/10.1016/j.xcrm.2023.101352DOI Listing

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