Increase of Ceramide in the Liver and Plasma after Carbon Tetrachloride Intoxication in the Rat

Ichi, Ikuyo; Nakahara, Kayoko; Fujii, Kozue; Iida, Chinatsu; Miyashita, Yayoi; Kojo, Shosuke

doi:10.3177/jnsv.53.53

Cited by 28 publications

(29 citation statements)

References 12 publications

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“…Considering the lower resonance of 128MHz at 3T and the observation of broad baseline positive MTR asym peak above 1.5ppm (blue curves in Figs 3b and 4b), it is possible that – NH has concomitant spill-over effects at higher chemical shifts and induces positive MTR asym . On the other hand, it was found by Ichi et al [45] that ceramide in the liver and plasma increased after CCl4 intoxication in the rat. It seems conflicting with the reduction of APTw MTR asym observed in our study.…”

Section: Discussionmentioning

confidence: 92%

Chemical exchange saturation transfer (CEST) MR technique for in-vivo liver imaging at 3.0 tesla

et al. 2015

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Purpose To evaluate Chemical Exchange Saturation Transfer (CEST) MRI for liver imaging at 3.0-T. Materials and Methods Images were acquired at offsets (n=41, increment=0.25ppm) from −5 to 5ppm using a TSE sequence with a continuous rectangular saturation pulse. Amide proton transfer-weighted (APTw) and GlycoCEST signals were quantified as the asymmetric magnetization transfer ratio (MTRasym) at 3.5ppm and the total MTRasym integrated from 0.5 to 1.5ppm, respectively, from the corrected Z-spectrum. Reproducibility was assessed for rats and humans. Eight rats were devoid of chow for 24-hours and scanned before and after fasting. Eleven rats were scanned before and after one-time CCl4 intoxication. Results For reproducibility, rat liver APTw and GlycoCEST measurements had 95% limits of agreement of −1.49% to 1.28% and −0.317% to 0.345%. Human liver APTw and GlycoCEST measurements had 95% limits of agreement of −0.842% to 0.899% and − 0.344% to 0.164%. After 24-hours fasting rat liver APTw and GlycoCEST signals decreased from 2.38±0.86% to 0.67±1.12% and from 0.34±0.26% to −0.18±0.37% respectively (p<0.05). After CCl4 intoxication rat liver APTw and GlycoCEST signals decreased from 2.46±0.48% to 1.10±0.77%, and from 0.34±0.23% to −0.16±0.51% respectively (p<0.05). Conclusion CEST liver imaging at 3.0-T showed high sensitivity for fasting as well as CCl4 intoxication.

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Section: Discussionmentioning

confidence: 92%

Chemical exchange saturation transfer (CEST) MR technique for in-vivo liver imaging at 3.0 tesla

et al. 2015

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“…A series of studies have shown that increased ceramide levels in both liver and plasma coincide with the development of liver dysfunction, hepatic insulin resistance, and steatosis in rodents (Ichi et al, 2007; Xia et al, 2014; Yetukuri et al, 2007). Previous work has identified the liver as a target of ceramide-induced insulin resistance and inhibition of whole-body ceramide synthesis reduces obesity-induced insulin resistance in rodents (Holland et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis

et al. 2015

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Sphingolipids have garnered attention for their role in insulin resistance and lipotoxic cell death. Aberrant accumulation of ceramides correlates with hepatic insulin resistance and steatosis. To further investigate the tissue-specific effects of local changes in ceramidase activity, we have developed transgenic mice inducibly expressing acid ceramidase, to trigger the deacylation of ceramides. This represents the first inducible genetic model that acutely manipulates ceramides in adult mouse tissues. Hepatic overexpression of acid ceramidase prevents hepatic steatosis and prompts improvements in insulin action in liver and adipose tissue. Conversely, overexpression of acid ceramidase within adipose tissue prevents hepatic steatosis and insulin resistance. Induction of ceramidase activity in either tissue promotes a lowering of hepatic ceramides and reduced activation of the ceramide-activated protein kinase C isoform PKC-zeta. These observations suggest the existence of a rapidly acting "crosstalk" between liver and adipose tissue sphingolipids, critically regulating glucose metabolism and hepatic lipid uptake.

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“…While some of these approaches may be used to analyze total ceramide, they do not provide data on individual ceramide species [15, 21]. In addition, existing methods provide discrepant results for ceramide levels in different biological samples [22–24]. Recent developments in electrospray ionization tandem mass spectrometry (ESI-MS/MS) have helped resolve some of these limitations.…”

Section: Introductionmentioning

confidence: 99%

Quantification of ceramide species in biological samples by liquid chromatography electrospray ionization tandem mass spectrometry

Kasumov

Huang

Chung

et al. 2010

Analytical Biochemistry

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We present an optimized and validated liquid chromatography-electrospray ionization tandem mass spectrometric (LC-ESI-MS/MS) method for the simultaneous measurement of concentrations of different ceramide species in biological samples. The method of analysis of tissue samples is based on Bligh and Dyer extraction, reverse-phase HPLC separation and multiple reaction monitoring of ceramides. Preparation of plasma samples also requires isolation of sphingolipids by silica gel column chromatography prior to LC-ESI-MS/MS analysis. The limits of detection and quantification are in a range of 5-50 pg/ml for distinct ceramides. The method was reliable for inter-assay and intra-assay precision, accuracy and linearity. Recovery of ceramide subspecies from human plasma, rat liver and muscle tissue were 78-91%, 70-99%, and 71-95%, respectively. The separation and quantification of several endogenous long-chain and very-long-chain ceramides using two non-physiological odd chain ceramide (C17 and C25) internal standards was achieved within a single 21 min chromatographic run. The technique was applied to quantify distinct ceramide species in different rat tissues (muscle, liver, and heart) and in human plasma. Using this analytical technique we demonstrated that a clinical exercise training intervention reduces the levels of ceramides in plasma of obese adults. This technique could be extended for quantification of other ceramides and sphyngolipids with no significant modification.

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Increase of Ceramide in the Liver and Plasma after Carbon Tetrachloride Intoxication in the Rat

Cited by 28 publications

References 12 publications

Chemical exchange saturation transfer (CEST) MR technique for in-vivo liver imaging at 3.0 tesla

Chemical exchange saturation transfer (CEST) MR technique for in-vivo liver imaging at 3.0 tesla

Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis

Quantification of ceramide species in biological samples by liquid chromatography electrospray ionization tandem mass spectrometry

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