The Detrimental Role Played by Lipocalin-2 in Alcoholic Fatty Liver in Mice.

The Detrimental Role Played by Lipocalin-2 in Alcoholic Fatty Liver in Mice.

Cai Yan; Jogasuria Alvin; Yin Huquan; Xu Ming-Jiang; Hu Xudong; Wang Jiayou; Kim Chunki; Wu Jiashin; Lee Kwangwon; Gao Bin; You Min

The American journal of pathology

2016

2016-09

We have previously shown that the ethanol-mediated elevation of lipocaline-2 (LCN2) is closely associated with the development of alcoholic fatty liver disease (AFLD) in mice. Herein, we aimed to understand the functional significance of LCN2 induction by ethanol and to explore its underlying mechanisms. We evaluated the effects of LCN2 in an in vitro cellular alcoholic steatosis model and in an animal study using wild-type and LCN2 knockout mice fed for 4 weeks with an ethanol-supplemented Lieber-DeCarli diet. In the cellular model of alcoholic steatosis, recombinant LCN2 or overexpression of LCN2 exacerbated ethanol-induced fat accumulation, whereas knocking down LCN2 prevented steatosis in hepatocytes exposed to ethanol. Consistently, removal of LCN2 partially but significantly alleviated alcoholic fatty liver injury in mice. Mechanistically, LCN2 mediates detrimental effects of ethanol in the liver via disrupted multiple signaling pathways, including aberrant nicotinamide phosphoribosyltransferase-sirtuin 1 axis, perturbed endocrine metabolic regulatory fibroblast growth factor 15/19 signaling, and impaired chaperone-mediated autophagy. Finally, compared with healthy human livers, liver samples from patients with AFLD had lower gene expression of several

Alcoholic/*metabolism; Animal; Animals; Blotting; Disease Models; Fatty Liver; Humans; Inbred C57BL; Knockout; Lipocalin-2/*metabolism; Mice; Polymerase Chain Reaction; Western

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2417–2428

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