Comprehensive lipidomics reveals phenotypic differences in hepatic lipid turnover in ALD and NAFLD during alcohol intoxication

Israelsen, Mads; Kim, Min; Suvitaival, Tommi; Madsen, Bjørn Stæhr; Hansen, Camilla Dalby; Torp, Nikolaj; Trošt, Kajetan; Thiele, Maja; Hansen, Torben; Legido‐Quigley, Cristina; Krag, Aleksander

doi:10.1016/j.jhepr.2021.100325

Cited by 27 publications

(21 citation statements)

References 36 publications

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“…In the present study, we also found that the 3 changed LPCs and 3 LPEs in response to alcohol exposure were all down-regulated. Compared with the effects on TAGs and free fatty acids metabolism, the effect of alcohol intake on LPC and LPE in liver is less well established but may be increased [ 7 , 25 ]. LPC and LPE always server as the precursors of lysophosphatidic acid (LPA).…”

Section: Discussionmentioning

confidence: 99%

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Absolute quantitative lipidomics reveals lipids profiling in liver of mice with early-stage alcoholic liver disease

et al. 2022

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Background Alcoholic liver disease (ALD) is one of the most prevalent chronic liver disease worldwide. Alcohol-induced alterations in hepatic lipids play an important role in ALD develpoment and progression. The present study aimed to thoroughly describe the changes of lipid profiling in liver of mice with early-stage alcoholic liver disease. Methods C57BL/6J male mice aged 7-week were randomized into alcohol-fed (AF) group and pair-fed control group (PF) (n = 10 per group). The early stage of ALD was induced with Lieber-DeCarli liquid diet. The lipids profiling was analyzed by absolute quantitative lipidomics with UHPLC-QTRAP-MS/MS. Results Alcohol intake significantly increased the levels of alanine aminotransferase (ALT) in plasma, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and triacylglycerols (TAG) levels in liver. Lipidomis analyses showed that 41 TAGs were up-regulated and 8 TAGs were down-regulated in response to alcohol intake. The 8 decreased TAGs were with more double bond, longer carbon chain length and mostly contained docosahexaenoic acid (C22:6n-3) and eicosapentaenoic acid (C20:5n-3), compared with the up-regulated TAGs. Furthermore, the down-regulated TAG(56:9)_FA20:5 was inversely associated with ALT and IL-6 levels. In addition, several altered lysophosphatidylcholines (LPC), lysophosphatidylethanolamines (LPE) and hexosylceramides (HCER) were all significantly decreased in response to alcohol consumption, especially HCer(18:1/22:0), with the top reduction among all the down-regulated lipids. Conclusions These findings suggest that not only the up-regulated lipids, alcohol-induced reduction in some specific lipids might also contribute to the ALD development, especially TAG(56:9)_FA20:5 and HCer(18:1/22:0). Their physiological functions and effects on ALD development warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

“…Evidences from animal experiments have shown the complex interaction between alcohol and hepatic lipid metabolism [ 7 ]. It has been proposed that alcohol has distinct effects on different types of fatty acids, according to the carbon length and degree of unsaturation [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Absolute quantitative lipidomics reveals lipids profiling in liver of mice with early-stage alcoholic liver disease

et al. 2022

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“… 78 Ethanol increases the uptake of FAs by the liver in vivo 79 and in vitro 80 leading to intrahepatic accumulation of TGs. 81 Abstinence has been shown to reduce serum FA and LPC levels, while TGs stay elevated 82 in patients with ALD ( Table 1 ). Moreover, in several models, FA synthesis pathways are significantly upregulated in mice fed alcohol ad libitum in their drinking water.…”

Section: Lipid Alterations In Liver Diseases Associated With the Deve...mentioning

confidence: 99%

Lipid alterations in chronic liver disease and liver cancer

2022

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“…An overview of the study design and setup can be seen in Figure 1. Results of the primary study are reported elsewhere 17 . The 48‐hour alcohol abstinence was confirmed by measuring blood ethanol levels on the day of the investigation before the start of the study.…”

Section: Methodsmentioning

confidence: 99%

“…Results of the primary study are reported elsewhere. 17 The 48-hour alcohol abstinence was confirmed by measuring blood ethanol levels on the day of the investigation before the start of the study. The intervention was in the form of a weight adjusted ethanol-NaCl mixture that was administered via a nasogastric tube and infusion pump.…”

Section: Investigationsmentioning

confidence: 99%

Binge drinking induces an acute burst of markers of hepatic fibrogenesis (PRO‐C3)

Torp

Israelsen

Nielsen

et al. 2021

Liver International

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Background & Aims Binge drinking is associated with an increased risk of liver disease. Morbidity and mortality of alcohol‐related liver disease (ALD) is associated with collagen deposition in the hepatic extracellular matrix (ECM). However, the acute effects of binge drinking on ECM turnover are unknown. We aimed to investigate the effects on hepatic ECM turnover following a binge drinking episode. Methods We performed a pathophysiological intervention study with 15 non‐alcoholic fatty liver disease (NAFLD) patients, 15 ALD patients and 10 healthy controls. We used 40% ethanol in 9 mg/mL NaCl administered through a nasogastric tube to simulate binge drinking. Hepatic vein catheterisation allowed simultaneous hepatic‐ and systemic vein sampling. Markers of ECM formation and degradation were measured with competitive ELISA. Results The interstitial matrix formation marker PRO‐C3 increased by 1.2 ng/mL (10%, P < .001) 24 hours after binge drinking. In participants with existing liver fibrosis determined by elevated baseline PRO‐C3, hepatic levels increased by 0.09 ng/mL (95% CI: 0.03‐0.15, P = .005) while systemic PRO‐C3 decreased 0.11 ng/mL (95% CI: −0.15 to −0.06, P < .001) in 3 hours. PRO‐C8 increased by 30% (+0.9 ng/mL, P = .014) in liver‐diseased patients with F0‐F1 but not in any other group. Twenty‐four‐hour changes in systemic C3M and PRO‐C3 were not associated (P = .911). Conclusions Binge drinking induced an acute burst of PRO‐C3 in healthy individuals and patients with liver disease. Markers of ECM degradation were not correlated to markers of ECM formation, suggesting that even a single episode of binge drinking promotes excessive hepatic fibrogenesis.

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Comprehensive lipidomics reveals phenotypic differences in hepatic lipid turnover in ALD and NAFLD during alcohol intoxication

Cited by 27 publications

References 36 publications

Absolute quantitative lipidomics reveals lipids profiling in liver of mice with early-stage alcoholic liver disease

Absolute quantitative lipidomics reveals lipids profiling in liver of mice with early-stage alcoholic liver disease

Lipid alterations in chronic liver disease and liver cancer

Binge drinking induces an acute burst of markers of hepatic fibrogenesis (PRO‐C3)

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