Hepatic phospholipids in alcoholic liver disease assessed by proton-decoupled 31P magnetic resonance spectroscopy

Schlemmer, Heinz Peter; Sawatzki, Tanja; Sammet, Steffen; Dornacher, Ines; Bachert, Peter; Kaick, G. van; Waldherr, Rüdiger; Seitz, Helmut K.

doi:10.1016/j.jhep.2004.12.032

Cited by 36 publications

(28 citation statements)

References 40 publications

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“…We observed some changes in the levels of these molecules in liver cirrhosis. Similar alterations in the levels of phospholipid precursors have been reported both 'in vitro' and 'in vivo' in previous studies (42,43). The interpretation of variations in these signals is not trivial.…”

Section: Discussionsupporting

confidence: 85%

Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies

Monleνn

2010

Int J Mol Med

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Abstract. Among the different processes occurring during the evolution of liver disease, fibrosis has a predominant role. Liver fibrosis mechanisms are fairly constant irrespective of the underlying etiology. Cirrhosis is the end-stage of this reaction. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. The aim of this study was to demonstrate the applicability of 1 H high resolution magic angle spinning (HR-MAS) NMR spectroscopy in the biochemical profile determination of human liver needle biopsy samples for the characterization of metabolic alterations related to the severity of liver disease. We recorded and analyzed HR-MAS spectra of 68 liver tissue samples obtained by needle biopsy from patients with chronic liver disease. Multivariate analysis was applied to these data to obtain discrimination patterns and to reveal relevant metabolites. The metabolic characterization of liver tissue from needle biopsies by HR-MAS NMR spectroscopy provided differential patterns for cirrhotic and non-cirrhotic chronic liver disease tissue. Metabolites closely related to the liver metabolism such as some fatty acids, glucose and amino acids show differences between the two groups. Phospholipid precursors, which have been previously correlated with hepatic lesions also show differences. Furthermore, the correlation between histologically assessed liver disease stages and the levels of the most discriminative metabolites show that liver dysfunction is present at the initial stages of chronic hepatic lesions. Overall, this work suggests that the additional information obtained by NMR metabolomics applied to needle biopsies of human liver may be useful for assessing metabolic alterations and liver dysfunction in chronic liver disease. IntroductionThe liver is among the most metabolically diverse organs of the body and is involved in many critical metabolic processes (1). One of its major roles is storing endogenous fuels of the body. In addition, the liver acts as a major distribution center for exogenous energy supplies. The liver may be affected by many pathological aggressions. Liver dysfunction results in a variety of clinical signs and symptoms. However, some of these pathologies pose a diagnostic challenge as many different diseases show similar clinical signs (2-4). Moreover, liver biopsy assessment involves some degree of complication because of the proliferation of different grading and staging schemes (5-7). Metabolic alterations produced by liver disease may help clinicians better characterize the disease. Among the different processes occurring during the evolution of liver disease, fibrosis takes a predominant role. Liver fibrosis is characterized by the replacement of liver tissue by fibrous scar tissue as well as regenerative nodules, leading to progressive loss of liver function and to altered liver metabolism (8-11). Liver fibrosis induction mechanisms are fairly constant irrespectivel...

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Section: Discussionsupporting

confidence: 85%

Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies

Monleνn

2010

Int J Mol Med

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“…ALD-associated reductions in hepatic phosphatidylcholine could be mediated by lower production rates of phosphocholine from phosphoethanolamine due to acetaldehyde mediated inhibition of phosphoethanolamine-N-methyltransferase (PEMT). Furthermore, in humans, 1 H-31 P magnetic resonance spectroscopic imaging demonstrated higher ratios of glycerophosphorylethanolamine/ glycerophosphorylcholine (GPE/GPC) in both cirrhotic and noncirrhotic cases of ALD, and selectively elevated phosphoethanolamine/phosphocholine ratios only in cirrhotics with ALD relative to controls [51]. Although we did not conduct a broad investigation of all lipid ion profiles, data from the previous and current studies strongly suggest that disease/exposure-related abnormalities in hepatic phospholipid composition may be detectable via noninvasive imaging with results validated by MALDI-IMS.…”

Section: Discussionmentioning

confidence: 98%

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

Yalçın¹,

Nunez²,

Cornett³

2015

J Drug Alcohol Res

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Background. Ethanol, tobacco-specific nitrosamine ketone (NNK), and ethanol+NNK exposures cause steatohepatitis, suggesting that smoking can be a cofactor in alcoholic liver disease. Study design. We used MALDI-TOF imaging mass spectrometry (IMS) to characterize hepatic lipid profiles in steatohepatitis caused by ethanol, NNK, and ethanol+NNK. Results. Ethanol, NNK, and ethanol+NNK increased levels and altered the profiles of hepatic phospholipids. Ethanol caused striking accumulations of m/z 932.7 phosphatidylinositol (PI). NNK increased hepatic levels of PIs with m/z's of 934.8, 960.8, and 962.7. Relative abundance of PIs with m/z's of 857.9 or 883.7 increased progressively from control to NNK, then ethanol, and finally ethanol+NNK, indicating differential and additive effects of these exposures. In contrast, no differences occurred with respect to phosphatidylethanolamine (m/z 766.9), phosphatidylserine (m/z 810.9) or PIs with m/z of 960.8 or 962.7. Principal component analysis generated distinct exposure-related hepatic lipid profiles. Conclusion. MALDI-IMS could serve as a complementary diagnostic aid for differentiating underlying causes of steatohepatitis.

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“…The additional phase-encoding directions and the need for a large number of signal averages render MRSI acquisition extremely time consuming. As a tradeoff, MRSI data are frequently acquired at low spatial resolution with as few as 8 phase encoding steps in one dimension (159)(160)(161). The small coverage of the k-space with low resolution MRSI gives rise to side-lobes in the spatial response function (SRF), which causes significant cross-voxel contamination and thus poor localization precision.…”

Section: P-mrsi Methodsmentioning

confidence: 99%

Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: a methodology review

Liu

2017

Quant. Imaging Med. Surg.

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Many human diseases are caused by an imbalance between energy production and demand.Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) provide the unique opportunity for in vivo assessment of several fundamental events in tissue metabolism without the use of ionizing radiation. Of particular interest, phosphate metabolites that are involved in ATP generation and utilization can be quantified noninvasively by phosphorous-31 ( 31 P) MRS/MRI. Furthermore, 31 P magnetization transfer (MT) techniques allow in vivo measurement of metabolic fluxes via creatine kinase (CK) and ATP synthase. However, a major impediment for the clinical applications of 31 P-MRS/MRI is the prohibitively long acquisition time and/or the low spatial resolution that are necessary to achieve adequate signal-to-noise ratio. P-MRS/MRI techniques. Applications of these techniques to the investigation of a specific physiology/pathology will be discussed without detailed description. Interested readers are referred to recent review articles on the applications of 31 P-MRS/MRI in metabolic characterization of skeletal muscle (10-12), heart (13), brain (14), and liver (11), as well as in diseases such as cancer (15), heart failure (16), and obesity and diabetes (17,18). Historical perspectiveThe use of 31 P-MRS for metabolic investigations dates back to 1960. Cohn and Hughes were the first to obtain a high-resolution 31 P spectrum of a solution of ATP (19). In addition, they also observed a dependence of the chemical shifts of the phosphorus nuclei of ATP on the pH of the solution. In parallel to the early development of MRI methods by Lauterbur (20), the entire 1970s also witnessed the rapid advance of 31 P-MRS in metabolic investigation of a broad range of biological systems. In 1973, Moon and Richards performed the first 31 P-MRS study that measured intracellular pH in human red blood cells (21). In the following year, Henderson and colleagues obtained the first 31 P spectrum of ATP from human red blood cells (22). At the same time, the Oxford team led by Radda performed the first experiment to acquire 31 P spectra from an intact organ, i.e., the excised and superfused muscle of rat hindlimb (23). The first in vivo 31 P-MRS study was performed on mouse brain by Chance et al. (24). Within the short span of one decade, organelles including mitochondria (25,26) and chromaffin granules (27), cells including Escherichia coli (28), yeast (29), and hepatocytes (30), and organs including skeletal muscle (31,32), heart (33-35), brain (36), kidney (37), and liver (38,39) have all been studied using 31 P-MRS.It is worth noting that most of these organ studies were performed on excised organs to avoid the need for spatial localization. Although Lauterbur has demonstrated the feasibility of imaging water protons (20), it was considered impractical for 31 P imaging of living systems because of the low sensitivity and difficulties with spectral resolution.The 1980s began with the publication of two important studies that aimed a...

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Hepatic phospholipids in alcoholic liver disease assessed by proton-decoupled 31P magnetic resonance spectroscopy

Cited by 36 publications

References 40 publications

Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies

Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: a methodology review

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