Interstrain differences in the severity of liver injury induced by a choline‐ and folate‐deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism

Background and Objective : A Tibetan traditional herb named Swertia mussotii Franch., also called “Zangyinchen” by the local people of Qinghai-Tibet area, has been used to protect the liver from injury for many years. However, the curative effect and molecular mechanism of the herb have not been demonstrated clearly. Materials and Methods: In our study, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin levels were examined after S. mussotii Franch. treatment in the acute liver injury of the carbon tetrachloride-induced rat model. Then, Proteome Analysis was applied to explore the potential mechanism of SMT for hepatoprotective effects after iTRAQLC-MS/MS analysis (isobaric tag for relative and absolute quantification-liquid chromatograph-mass spectrometer with tandem mass spectrometry). Results: Serum results showed, alanine aminotransferase, aspartate aminotransferase, total bilirubin levels of rats with acute liver injury were all improved with SMT treatment. Moreover, Proteome Analysis suggested that, with S. Mussotii Franch. treatment, the levels of lipid catabolic process and lipid homeostasis were all enhanced. And the results of protein-protein interaction (PPI) analysis illustrated that these proteins assembled in PPI networks were found almost significantly enriched in response to lipid, negative regulation of lipase activity, response to lipopolysaccharide etc. Furthermore, the downregulated MRP14 and MRP8 proteins were found involved in the lipid metabolism, which may indicate the mechanism of SMT protection liver from ALI induced by carbon tetrachloride. Conclusion: SMT herb could play a role in hepatoprotection and alleviate the effect of acute liver injury by impacting the lipid metabolism associated biological process.

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Effect of Lactobacillus casei on lipid metabolism and intestinal microflora in patients with alcoholic liver injury

European Journal of Clinical Nutrition ◽

10.1038/s41430-020-00852-8 ◽

2021 ◽

Author(s):

Xuelong Li ◽

Ying Liu ◽

Xiaofei Guo ◽

Yan Ma ◽

Huaqi Zhang ◽

...

Keyword(s):

Lipid Metabolism ◽

Liver Injury ◽

Lactobacillus Casei ◽

Intestinal Microflora ◽

Alcoholic Liver Injury

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Lipidomics Analysis Indicates Disturbed Hepatocellular Lipid Metabolism in Reynoutria multiflora-Induced Idiosyncratic Liver Injury

Frontiers in Pharmacology ◽

10.3389/fphar.2020.569144 ◽

2020 ◽

Vol 11 ◽

Author(s):

Xiaofang Wu ◽

Yating Zhang ◽

Jiaqi Qiu ◽

Ya Xu ◽

Jing Zhang ◽

...

Keyword(s):

Lipid Metabolism ◽

Liver Injury ◽

Rat Liver ◽

High Performance ◽

Phospholipid Metabolism ◽

Polygonum Multiflorum ◽

Drug Induced ◽

Metabolic Characteristics ◽

Lipid Biomarker ◽

Q Exactive

The root of Reynoutria multiflora (Thunb.) Moldenke (syn.: Polygonum multiflorum Thunb., HSW) is a distinguished herb that has been popularly used in traditional Chinese medicine (TCM). Evidence of its potential side effect on liver injury has accumulated and received much attention. The objective of this study was to profile the metabolic characteristics of lipids in injured liver of rats induced by HSW and to find out potential lipid biomarkers of toxic consequence. A lipopolysaccharide (LPS)-induced rat model of idiosyncratic drug-induced liver injury (IDILI) was constructed and evident liver injury caused by HSW was confirmed based on the combination of biochemical, morphological, and functional tests. A lipidomics method was developed for the first time to investigate the alteration of lipid metabolism in HSW-induced IDILI rat liver by using ultra-high-performance liquid chromatography/Q-exactive Orbitrap mass spectrometry coupled with multivariate analysis. A total of 202 characterized lipids, including phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), sphingomyelin (SM), phosphatidylinositol (PI), lysophosphatidylinositol (LPI), phosphatidylserine (PS), phosphoglycerols (PG), and ceramide (Cer), were compared among groups of LPS and LPS + HSW. A total of 14 out 26 LPC, 22 out of 47 PC, 19 out of 29 LPE, 16 out of 36 PE, and 10 out of 15 PI species were increased in HSW-treated rat liver, which indicated that HSW may cause liver damage via interfering the phospholipid metabolism. The present work may assist lipid biomarker development of HSW-induced DILI and it also provide new insights into the relationships between phospholipid perturbation and herbal-induced idiosyncratic DILI.

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LIPID METABOLISM AND LIPOPROTEIN SUSCEPTIBILITY TO PEROXIDATION ARE AFFECTED BY A PROTEIN-DEFICIENT DIET IN THE RAT

Nutrition Research ◽

10.1016/s0271-5317(96)00239-4 ◽

1997 ◽

Vol 17 (1) ◽

pp. 125-135 ◽

Cited By ~ 12

Author(s):

Corinne Moundras ◽

Christian Demigné ◽

Christine Morand ◽

Marie-Anne Levrat ◽

Christian Rémésy

Keyword(s):

Lipid Metabolism ◽

Deficient Diet ◽

Protein Deficient Diet

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Phosphatidylcholine transfer protein/StarD2 promotes microvesicular steatosis and liver injury in murine experimental steatohepatitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00379.2016 ◽

2017 ◽

Vol 313 (1) ◽

pp. G50-G61 ◽

Cited By ~ 6

Author(s):

Hayley T. Nicholls ◽

Jason L. Hornick ◽

David E. Cohen

Keyword(s):

Liver Injury ◽

Lipid Droplets ◽

Plasma Concentrations ◽

Fibroblast Growth Factor 21 ◽

Wild Type ◽

Hepatocellular Injury ◽

Pathogenic Role ◽

Deficient Diet ◽

Transfer Protein ◽

Phosphatidylcholine Transfer Protein

Mice fed a methionine- and choline-deficient (MCD) diet develop steatohepatitis that recapitulates key features of nonalcoholic steatohepatitis (NASH) in humans. Phosphatidylcholine is the most abundant phospholipid in the surfactant monolayer that coats and stabilizes lipid droplets within cells, and choline is required for its major biosynthetic pathway. Phosphatidylcholine-transfer protein (PC-TP), which exchanges phosphatidylcholines among membranes, is enriched in hepatocytes. PC-TP also regulates fatty acid metabolism through interactions with thioesterase superfamily member 2. We investigated the contribution of PC-TP to steatohepatitis induced by the MCD diet. Pctp−/− and wild-type control mice were fed the MCD diet for 5 wk and were then euthanized for histopathologic and biochemical analyses, as well as determinations of mRNA and protein expression. Whereas all mice developed steatohepatitis, plasma alanine aminotransferase and aspartate aminotransferase activities were only elevated in wild-type mice, indicating that Pctp−/− mice were protected from MCD diet-induced hepatocellular injury. Reduced hepatotoxicity due to the MCD diet in the absence of PC-TP expression was further evidenced by decreased activation of c-Jun and reduced plasma concentrations of fibroblast growth factor 21. Despite similar total hepatic concentrations of phosphatidylcholines and other lipids, the relative abundance of microvesicular lipid droplets within hepatocytes was reduced in Pctp−/− mice. Considering that the formation of larger lipid droplets may serve to protect against lipotoxicity in NASH, our findings suggest a pathogenic role for PC-TP that could be targeted in the management of this condition. NEW & NOTEWORTHY Phosphatidylcholine-transfer protein (PC-TP) is a highly specific phosphatidylcholine-binding protein that we previously showed to regulate hepatocellular nutrient metabolism through its interacting partner thioesterase superfamily member 2 (Them2). This study identifies a pathogenic role for PC-TP, independent of Them2, in the methionine- and choline-deficient diet model of experimental steatohepatitis. Our current observations suggest that PC-TP promotes liver injury by mediating the intermembrane transfer of phosphatidylcholines, thus stabilizing more pathogenic microvesicular lipid droplets.

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Pulsatilla chinensis saponins cause liver injury through interfering ceramide/sphingomyelin balance that promotes lipid metabolism dysregulation and apoptosis

Phytomedicine ◽

10.1016/j.phymed.2020.153265 ◽

2020 ◽

Vol 76 ◽

pp. 153265 ◽

Cited By ~ 3

Author(s):

Dan Su ◽

Zhou Liao ◽

Binwei Feng ◽

Tingting Wang ◽

Baixi shan ◽

...

Keyword(s):

Lipid Metabolism ◽

Liver Injury ◽

Pulsatilla Chinensis

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A Discovery of Relevant Hepatoprotective Effects and Underlying Mechanisms of Dietary Clostridium butyricum Against Corticosterone-Induced Liver Injury in Pekin Ducks

Microorganisms ◽

10.3390/microorganisms7090358 ◽

2019 ◽

Vol 7 (9) ◽

pp. 358 ◽

Cited By ~ 2

Author(s):

Yanhan Liu ◽

Cun Liu ◽

Liqing Huang ◽

Zhaofei Xia

Keyword(s):

Oxidative Stress ◽

Lipid Metabolism ◽

Liver Injury ◽

Signaling Pathway ◽

Basal Diet ◽

Clostridium Butyricum ◽

Pekin Ducks ◽

Injury Model ◽

Hepatoprotective Effects ◽

Underlying Mechanisms

Clostridium butyricum (C. butyricum) can attenuate oxidative stress, inflammation, and hepatic fatty deposition in poultry, however, the underlying mechanisms for this in Pekin ducks remain unclear. This study evaluated these hepatoprotective effects and the underlying mechanisms in a corticosterone (CORT)-induced liver injury model in Pekin ducks fed a C. butyricum intervention diet. A total of 500 Pekin ducks were randomly divided into five groups: one group (CON group) was only provided with a basal diet, three groups were provided a basal diet with 200 mg/kg (LCB group), 400 mg/kg (MCB group), or 600 mg/kg (HCB group) C. butyricum, respectively, and one group was provided a basal diet with 150 mg/kg aureomycin (ANT group) for 42 d. At 37 days-old, all ducks received daily intraperitoneal injections of CORT for five days to establish a liver injury model. C. butyricum intervention alleviated liver injury by decreasing the liver organ indices, hepatic steatosis and hepatocyte necrosis, and improving liver function, antioxidant capacity, and inflammatory factors. Hepatic RNA-seq revealed 365 differentially expressed genes (DEGs) between the MCB and CON groups, with 229 up- and 136 down-regulated DEGs in the MCB group. Between the MCB and ANT groups, 407 DEGs were identified, including 299 up- and 108 down-regulated genes in MCB group. Some DEGs in the MCB group related to oxidative stress and inflammatory responses such as Sod3, Tlr2a/b, and Il10, which were up-regulated, while Apoa1, Cyp7a1, Acsl1/5, Fasn, Ppar-γ, and Scd, which are involved in lipid metabolism, were down-regulated, indicating that these genes were responsive to dietary C. butyricum for the alleviation of corticosterone-induced hepatic injury. Toll-like receptor signaling, PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor (PPAR) signaling pathway, adipocytokine and glycerophospholipid metabolism signaling pathway were significantly enriched in the MCB group. These findings indicate that C. butyricum intervention can protect Pekin ducks from corticosterone-induced liver injury by the modulation of immunoregulatory- and lipid metabolism-related genes and pathways.

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