Hyperglycemia aggravates acute liver injury by promoting liver‐resident macrophage NLRP3 inflammasome activation via the inhibition of AMPK/mTOR‐mediated autophagy induction

• DOI: 10.1111/imcb.12297
• Publication Date: 2019-10-18T10:45:23Z
• Authors: Qi Wang; Song Wei; Shun Zhou; Jiannan Qiu; Chenyu Shi; Rui Liu; Haoming Zhou; Ling Lu
• Keywords: Male; 0301 basic medicine; Inflammasomes; Autophagic Cell Death; Macrophages; TOR Serine-Threonine Kinases; Original Articles; AMP-Activated Protein Kinases; Liver Failure, Acute; 3. Good health; Mice; 03 medical and health sciences; Hyperglycemia; NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Signal Transduction

Abstract Although the detrimental effects of diabetes mellitus/hyperglycemia have been observed in many liver disease models, function and mechanism hyperglycemia regulating liver‐resident macrophages, Kupffer cells (KCs), thioacetamide ( TAA )‐induced injury remain largely unknown. In this study, we evaluated role NOD‐like receptor family pyrin domain‐containing 3 protein (NLRP3) inflammasome activation by inhibiting autophagy induction KC s ‐induced model. Type I diabetes/hyperglycemia was induced streptozotocin treatment. Compared with control group, hyperglycemic mice exhibited a significant increase intrahepatic inflammation injury. Enhanced NLRP detected from mice, as shown increased gene levels 3, cleaved caspase‐1, apoptosis‐associated speck‐like containing caspase recruitment domain interleukin ‐1β, compared mice. inhibition its antagonist CY ‐09 effectively suppressed attenuated Furthermore, inhibited revealed transmission electron microscope detection, decreased LC 3B expression p‐62 degradation isolated ‐stressed Interestingly, 5′ AMP‐activated kinase (AMPK) but enhanced mammalian target rapamycin (mTOR) found AMPK agonist 5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR) or mTOR signaling knockdown small interfering RNA restored activation, subsequently, s, leading to ultimately reduced Our findings demonstrated that aggravated acute promoting macrophage via / ‐mediated autophagy. This study provided novel for prevention toxin‐induced under hyperglycemia.