Date: Monday, June 3, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: The detrimental effects of diabetes mellitus/hyperglycemia include an increase in the oxidative stress response and an enhanced inflammatory response. Despite an increased understanding of the pathophysiology of toxin-induced liver injury, the role and underlying mechanism of hyperglycemia in regulating thioacetamide (TAA) induced liver injury remains unclear.
*Methods: Type I diabetes was induced by streptozotocin treatment. Hyperglycemic mice (STZ) and control group mice (CON) were subjected to TAA-induced acute liver injury model. Liver injury and NLRP3-mediated innate immune response were evaluated. RAW 264.7 cells were cultured with low (LG) or high glucose medium (HG), and the signaling pathways in regulating autophagy and NLRP3 activation were analyzed.
*Results: Compared to the CON group, STZ mice exhibited a significant increase in liver injury and intrahepatic inflammation post TAA treatment. HG RAW 264.7 cells showed much higher levels of TNF-α, IL-6 and NLRP3 activation. In contrast, autophagy were inhibited in HG RAW 264.7 cells. AMPK/mTOR signaling was found to be involved in inhibiting autophagy activation by high glucose treatment. Autophagy induction by mTOR-siRNA or AMPK agonist inhibited NLRP3 activation in HG RAW 264.7 cells.
*Conclusions: Hyperglycemia aggravated TAA-induced liver injury by autophagy inhibition, leading to NLRP3 activation in macrophages. These findings demonstrated APMK-mTOR dependent autophagy is a novel regulator of innate immunity in toxin-induced liver injury in diabetes mellitus.
To cite this abstract in AMA style:ZHOU H, Wang Q, Liu R, Zhou S, Cheng F, Wang X, Lu L. Hyperglycemia Aggravates Acute Liver Injury by Promoting Macrophage NLRP3 Activation via AMPK/mTOR-Dependent Autophagy Inhibition [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/hyperglycemia-aggravates-acute-liver-injury-by-promoting-macrophage-nlrp3-activation-via-ampk-mtor-dependent-autophagy-inhibition/. Accessed October 23, 2020.
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