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Leptin Induces NAFLD Progression through Infiltrated CD8+ T Lymphocytes Mediating Pyroptotic-like Cell Death of Hepatocytes and Macrophages

Authors: Qinghui Zhang, Jianjun Wang, Feng Huang, Yongliang Yao, Ling Xu

Online: https://www.dldjournalonline.com/article/S1590-8658(20)30979-8/fulltext

Issue: Digestive and Liver Disease. 2020 Nov 7;S1590-865


Background: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease, which causes serious health problems worldwide. Hyperleptinemia and inflammatory stress are crucial in the progression of NAFLD. However, the relationship between leptin and immune cells or hepatocytes is still unclear.

Aims: This study aimed to clarify the regulatory mechanism of leptin-mediated disease progression through immune cells and its relationship with hepatocytes.

Methods: An NAFLD rat model was established to verify the relationship between hyperleptinemia and CD8+ T lymphocytes and cytokines in liver tissue. CD8+ T lymphocytes isolated from blood mononuclear cells were co-cultured with macrophages or hepatocytes stimulated with leptin or treated with granzyme inhibitors to observe target cell morphology and expression of pivotal protein family members.

Results: CD8+ T lymphocyte infiltration positively correlated with blood leptin, IL-18 and IL-1β levels and was related to macrophage recruitment and differentiation in a rat model of NAFLD. Leptin could induce activated caspase-1 and caspase-3 in hepatocytes and trigger hepatocyte pyroptosis.

Conclusions: Leptin may regulate the pyroptotic-like death of macrophages and hepatocytes through CD8+ T lymphocytes in NAFLD progression. The intervention of related pathways of leptin and immune cells may provide a promising strategy for treating NAFLD.

Keywords: Hepatocyte; Leptin; NAFLD; Pyroptosis.

Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.