Myeloid Cell-Specific Lipin-1 Deficiency Stimulates Endocrine Adiponectin-FGF15 Axis and Ameliorates Ethanol-Induced Liver Injury in Mice.

Title

Myeloid Cell-Specific Lipin-1 Deficiency Stimulates Endocrine Adiponectin-FGF15 Axis and Ameliorates Ethanol-Induced Liver Injury in Mice.

Creator

Wang Jiayou; Kim Chunki; Jogasuria Alvin; Han Yoonhee; Hu Xudong; Wu Jiashin; Shen Hong; Chrast Roman; Finck Brian N; You Min

Publisher

Scientific reports

Date

2016
2016-09

Description

Lipin-1 is a phosphatidate phosphohydrolase (PAP) required for the generation of diacylglycerol during glycerolipid synthesis, and exhibits dual functions in the regulation of lipid metabolism. Lipin-1 has been implicated in the pathogenesis of alcoholic liver disease (ALD). In the present study, we assessed lipin-1 function in myeloid cells in ALD using a myeloid cell-specific lipin-1 knockout (mLipin-1KO) mouse model. Utilizing the Gao-binge ethanol feeding protocol, matched mLipin-1KO mice and littermate loxP control (WT) mice were pair-fed with either an ethanol-containing diet or an ethanol-free diet (control). Surprisingly, deletion of lipin-1 in myeloid cells dramatically attenuated liver inflammatory responses and ameliorated liver injury that would normally occur following the ethanol feeding protocol, but slightly exacerbated the ethanol-induced steatosis in mice. Mechanistically, myeloid cell-specific lipin-1 deficiency concomitantly increased the fat-derived adiponectin and ileum-derived fibroblast growth factor (FGF) 15. In concordance with concerted elevation of circulating adiponectin and FGF15, myeloid cell-specific lipin-1 deficiency diminished hepatic nuclear factor kappa B (NF-kappaB) activity, limited liver inflammatory responses, normalized serum levels of bile acids, and protected mice from liver damage after ethanol challenge. Our novel data demonstrate that myeloid cell-specific deletion of lipin-1 ameliorated inflammation and alcoholic hepatitis in mice via activation of endocrine adiponectin-FGF15 signaling.

Subject

Adiponectin/*blood; Alcoholic/blood/*genetics/metabolism; Animal; Animals; Disease Models; Fatty Liver; Fibroblast Growth Factors/*blood; Gene Knockout Techniques; Lipid Metabolism; Male; Mice; Myeloid Cells/*metabolism; NF-kappa B/metabolism; Nuclear Proteins/*deficiency; Organ Specificity; Phosphatidate Phosphatase/*deficiency; Signal Transduction

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

34117–34117

Volume

6

Citation

Wang Jiayou; Kim Chunki; Jogasuria Alvin; Han Yoonhee; Hu Xudong; Wu Jiashin; Shen Hong; Chrast Roman; Finck Brian N; You Min, “Myeloid Cell-Specific Lipin-1 Deficiency Stimulates Endocrine Adiponectin-FGF15 Axis and Ameliorates Ethanol-Induced Liver Injury in Mice.,” NEOMED Bibliography Database, accessed January 27, 2021, https://neomed.omeka.net/items/show/4007.

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