Age-related sensitivity to endotoxin-induced XXXX : Implication of inflammasome/ @entity3426 for @entity1560 .

@entity32 @entity3725 @entity1560 @entity409 @entity3426 @entity35 @entity7268 @entity99 @entity37850
UNASSIGNED: Aging is associated with increased vulnerability to inflammatory challenge. However, the effects of altered inflammatory response on the metabolic status of tissues or organs are not well documented. In this study, we present evidence demonstrating that lipopolysaccharide (LPS)-induced upregulation of the inflammasome/ @entity3426 pathway is accompanied with an increased inflammatory response and abnormal lipid accumulation in livers of aged @entity35 . To monitor the effects of aging on LPS-induced @entity32 , we administered LPS (2  mg  kg(-1) ) to young (6-month old) and aged (24-month old) @entity35 and found abnormal lipid metabolism in only aged @entity35 with increased lipid accumulation in the liver. This lipid accumulation in the liver was due to the dysregulation of @entity3725 and @entity37850 . We also observed severe @entity409 in aged @entity35 as indicated by increased ALT levels in serum and increased Kupffer cells in the liver. Importantly, among many @entity32 -associated factors, the aged @entity35 liver showed chronically increased @entity3426 production. Increased levels of @entity3426 were caused by the upregulation of @entity7268 activity and inflammasome activation. In vitro studies with HepG2 cells demonstrated that treatment with @entity3426 significantly induced lipid accumulation in hepatocytes through the regulation of @entity3725 and @entity37850 . In summary, we demonstrated that @entity99 and lipid accumulation were associated with a chronically overactive inflammasome/ @entity3426 pathway in aged @entity35 livers. Based on the present findings, we propose a mechanism of aging-associated progression of @entity1560 induced by endotoxin, delineating a pathogenic role of the inflammasome/ @entity3426 pathway involved in lipid accumulation in the liver.
