Abstract | BACKGROUND & AIMS: METHODS: We induced alcoholic liver injury in male Sirt1LKO and control mice, placing them on Lieber-DeCarli ethanol-containing diets for 10 days and then administering a single dose of ethanol (5 g/kg body weight) via gavage. Liver and serum samples were collected. We also measured messenger RNA levels of SIRT1, SFRS10, and lipin-1β and lipin-1α in liver samples from patients with alcoholic hepatitis and individuals without alcoholic hepatitis (controls). RESULTS: On the ethanol-containing diet, livers of Sirt1LKO mice accumulated larger amounts of hepatic lipid and expressed higher levels of inflammatory cytokines than control mice; serum of Sirt1LKO mice had increased levels of alanine aminotransferase and aspartate aminotransferase. Hepatic deletion of SIRT1 exacerbated ethanol-mediated defects in lipid metabolism, mainly by altering the function of lipin-1, a transcriptional regulator of lipid metabolism. In cultured mouse AML-12 hepatocytes, transgenic expression of SIRT1 prevented fat accumulation in response to ethanol exposure, largely by reversing the aberrations in lipin-1 signaling induced by ethanol. Liver samples from patients with alcoholic hepatitis had reduced levels of SIRT1 and a higher ratio of Lpin1β/α messenger RNAs than controls. CONCLUSIONS:
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Authors | Huquan Yin, Ming Hu, Xiaomei Liang, Joanne M Ajmo, Xiaoling Li, Ramon Bataller, Gemma Odena, Stanley M Stevens Jr, Min You |
Journal | Gastroenterology
(Gastroenterology)
Vol. 146
Issue 3
Pg. 801-11
(Mar 2014)
ISSN: 1528-0012 [Electronic] United States |
PMID | 24262277
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Nerve Tissue Proteins
- Nuclear Proteins
- RNA-Binding Proteins
- TRA2B protein, human
- Serine-Arginine Splicing Factors
- Ethanol
- Lpin1 protein, mouse
- Phosphatidate Phosphatase
- Sirt1 protein, mouse
- Sirtuin 1
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Topics |
- Animals
- Disease Models, Animal
- Endoplasmic Reticulum Stress
(physiology)
- Ethanol
(adverse effects)
- Fatty Liver, Alcoholic
(etiology, metabolism, physiopathology)
- Hepatocytes
(metabolism)
- Humans
- Lipid Metabolism
(physiology)
- Liver
(enzymology, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Nerve Tissue Proteins
(metabolism)
- Nuclear Proteins
(metabolism)
- Oxidative Stress
(physiology)
- Phosphatidate Phosphatase
(metabolism)
- RNA-Binding Proteins
(metabolism)
- Serine-Arginine Splicing Factors
- Signal Transduction
(physiology)
- Sirtuin 1
(deficiency, genetics, metabolism)
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