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Myeloid Cell-Specif...
Myeloid Cell-Specific Lipin-1 Deficiency Stimulates Endocrine Adiponectin-FGF15 Axis and Ameliorates Ethanol-Induced Liver Injury in Mice
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Wang, JY (author)
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Kim, C (author)
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Jogasuria, A (author)
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Han, Y (author)
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Hu, XD (author)
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Wu, JS (author)
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Shen, H (author)
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- Chrast, R (author)
- Karolinska Institutet
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Finck, BN (author)
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You, M (author)
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(creator_code:org_t)
- 2016-09-26
- 2016
- English.
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 34117-
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https://doi.org/10.1...
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Abstract
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- 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-κB) 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.
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- By the author/editor
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Wang, JY
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Kim, C
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Jogasuria, A
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Han, Y
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Hu, XD
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Wu, JS
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show more...
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Shen, H
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Chrast, R
-
Finck, BN
-
You, M
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show less...
- Articles in the publication
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Scientific repor ...
- By the university
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Karolinska Institutet