Variations in hepatic lipid species of age-matched male mice fed a methionine-choline-deficient diet and housed in different animal facilities

Rein-Fischboeck, Lisa; Haberl, Elisabeth M.; Pohl, Rebekka; Feder, Susanne; Liebisch, Gerhard; Krautbauer, Sabrina; Buechler, Christa

doi:10.1186/s12944-019-1114-4

Cited by 12 publications

(9 citation statements)

References 64 publications

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“…A decline of hepatic PC levels was reported in human NASH [36][37][38]. Hepatic PC was reduced in some murine NASH models [5,[44][45][46][47] and was low in the LMCD model studied herein. PC depletion is, however, not mandatory for NASH development and disease progression at least in the murine liver [48].…”

Section: Discussionsupporting

confidence: 55%

“…Though low LPC levels were indeed observed in the current model, Puri et al described higher LPC in human NASH liver [37]. Murine studies identified increased and unchanged LPC in NASH liver [5,37,38]. Thus, the source and regulation of hepatic LPC in NASH remains unknown.…”

Section: Discussionmentioning

confidence: 55%

“…Dietary animal models are widely used to study NASH pathogenesis and feeding mice a chow deficient in choline and methionine is the method of choice [4]. Unfortunately, by two weeks animals loose about 10 to 20% of their body weight [4][5][6]. To overcome excessive weight loss, the L-amino acid-defined, choline-deficient, dietary mouse model was established [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Hepatic lipid profile in mice fed a choline-deficient, low-methionine diet resembles human non-alcoholic fatty liver disease

et al. 2020

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Background Emerging data support a role for lipids in non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in humans. With experimental models such data can be challenged or validated. Mice fed a low-methionine, choline-deficient (LMCD) diet develop NASH and, when injected with diethylnitrosamine (DEN), HCC. Here, lipidomic analysis was used to elucidate whether the NASH and HCC associated lipid derangements resemble the lipid profile of the human disease. Methods Lipids were measured in the liver of mice fed a control or a LMCD diet for 16 weeks. DEN was injected at young age to initiate hepatocarcinogenesis. DEN treatment associated changes of the lipid composition and the tumor lipidome were evaluated. Results LMCD diet fed mice accumulated ceramides and triacylglycerols in the liver. Phospholipids enriched with monounsaturated fatty acids were also increased, whereas hepatic cholesterol levels remained unchanged in the LMCD model. Phosphatidylcholine and lysophosphatidylcholine concentrations declined in the liver of LMCD diet fed mice. The changes of most lipids associated with LMCD diet feeding were similar between water and DEN injected mice. Several polyunsaturated (PU) diacylglycerol species were already low in the liver of DEN injected mice fed the control diet. Tumors developed in the liver of LMCD diet fed mice injected with DEN. The tumor specific lipid profile, however, did not resemble the decrease of ceramides and PU phospholipids, which was consistently described in human HCC. Triacylglycerols declined in the cancer tissues, which is in accordance with a low expression of lipogenic enzymes in the tumors. Conclusions The LMCD model is suitable to study NASH associated lipid reprogramming. Hepatic lipid profile was modestly modified in the DEN injected mice suggesting a function of these derangements in carcinogenesis. Lipid composition of liver tumors did not resemble the human HCC lipidome, and most notably, lipogenesis and triacylglycerol levels were suppressed.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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Hepatic lipid profile in mice fed a choline-deficient, low-methionine diet resembles human non-alcoholic fatty liver disease

et al. 2020

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“…This dietary model was used in our group before [ 35 , 36 ]. Hepatic expression of F4/80, CD68, TNF, and TGFβ mRNA were induced and triglycerides accumulated in the liver.…”

Section: Methodsmentioning

confidence: 99%

Hepatocyte expressed chemerin-156 does not protect from experimental non-alcoholic steatohepatitis

et al. 2022

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Non-alcoholic steatohepatitis (NASH) is a rapidly growing liver disease. The chemoattractant chemerin is abundant in hepatocytes, and hepatocyte expressed prochemerin protected from NASH. Prochemerin is inactive and different active isoforms have been described. Here, the effect of hepatocyte expressed muChem-156, a highly active murine chemerin isoform, was studied in the methionine–choline deficient dietary model of NASH. Mice overexpressing muChem-156 had higher hepatic chemerin protein. Serum chemerin levels and the capability of serum to activate the chemerin receptors was unchanged showing that the liver did not release active chemerin. Notably, activation of the chemerin receptors by hepatic vein blood did not increase in parallel to total chemerin protein in patients with liver cirrhosis. In experimental NASH, muChem-156 had no effect on liver lipids. Accordingly, overexpression of active chemerin in hepatocytes or treatment of hepatocytes with recombinant chemerin did not affect cellular triglyceride and cholesterol levels. Importantly, overexpression of muChem-156 in the murine liver did not change the hepatic expression of inflammatory and profibrotic genes. The downstream targets of chemerin such as p38 kinase were neither activated in the liver of muChem-156 producing mice nor in HepG2, Huh7 and Hepa1-6 cells overexpressing this isoform. Recombinant chemerin had no effect on global gene expression of primary human hepatocytes and hepatic stellate cells within 24 h of incubation. Phosphorylation of p38 kinase was, however, increased upon short-time incubation of HepG2 cells with chemerin. These findings show that muChem-156 overexpression in hepatocytes does not protect from liver steatosis and inflammation.

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“…Regarding their involvement in atherogenesis, they participate by two mechanisms: one directly on the vascular wall through transcytosis of ox-LDL, and second through insulin sensitivity and dyslipidemia [44]. In different circumstances, data shows that ox-LDL is present in the atherosclerotic plaque, and that increased blood concentration especially in patients with NAFLD, mediates activation of LacCer synthase and thus, the development of ATS [45,46]. Ox-LDL can lead to arterial endothelium damage by inducing cell proliferation and can establish the secretion of TNFα, a result of uptake in macrophages and accumulation in blood flow.…”

Section: Ceramides In Nafld-ats Developmentmentioning

confidence: 99%

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (ATS) are worldwide known diseases with increased incidence and prevalence. These two are driven and are interconnected by multiple oxidative and metabolic functions such as lipotoxicity. A gamut of evidence suggests that sphingolipids (SL), such as ceramides, account for much of the tissue damage. Although in humans they are proving to be accurate biomarkers of adverse cardiovascular disease outcomes and NAFLD progression, in rodents, pharmacological inhibition or depletion of enzymes driving de novo ceramide synthesis prevents the development of metabolic driven diseases such as diabetes, ATS, and hepatic steatosis. In this narrative review, we discuss the pathways which generate the ceramide synthesis, the potential use of circulating ceramides as novel biomarkers in the development and progression of ATS and related diseases, and their potential use as therapeutic targets in NAFDL-ATS development which can further provide new clues in this field.

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Variations in hepatic lipid species of age-matched male mice fed a methionine-choline-deficient diet and housed in different animal facilities

Cited by 12 publications

References 64 publications

Hepatic lipid profile in mice fed a choline-deficient, low-methionine diet resembles human non-alcoholic fatty liver disease

Hepatic lipid profile in mice fed a choline-deficient, low-methionine diet resembles human non-alcoholic fatty liver disease

Hepatocyte expressed chemerin-156 does not protect from experimental non-alcoholic steatohepatitis

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

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