Differential Metabolic Pathways and Metabolites in a C57BL/6J Mouse Model of Alcoholic Liver Disease

Abstract

The present study was supported by the National Natural Science Foundation of China [81873570] and grants for the 4 th Excellent Scientific Research of QNBJRC from Anhui Medical University [2013500023]. This study was carried out at the Basic SPF Animal Laboratory of Anhui Medical University. Animal ethics approval number: LLSC20180145 Background:Alcoholic liver disease (ALD), an important cause of acute or chronic liver injury, results from binge drinking or long-term alcohol consumption. To date, there is no well-established mouse model with a comprehensive metabolic profile that mimics ALD in humans. This study aimed to explore the differential metabolic pathways and related differential metabolites in the liver of an ALD mouse model. Material/Methods:A C57BL/6J mouse model of ALD was induced by alcohol feeding for 10 days plus binge alcohol feeding. The metabolomic profiles in the liver of the ALD mouse model was detected through ultra-high-pressure liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS). Results:A total 35 metabolites were significantly altered during the development of ALD. These metabolites were correlated to multiple metabolic pathways, including purine metabolism, the pentose phosphate pathway, cysteine and methionine metabolism, D-glutamine and D-glutamate metabolism, pyrimidine metabolism, and vitamin B6 metabolism. Conclusions:The findings of the present study reveal potential biomarkers of ALD, and provide further insights into the pathogenesis of ALD.

Metabolomics Study of Serum from a Chronic Alcohol-Fed Rat Model Following Administration of Defatted Tenebrio molitor Larva Fermentation Extract

“…A recent study suggests that potential pathways associated with alcoholic liver injury, including the D-glutamine, D-glutamate, cysteine, and methionine metabolisms in the liver [16]; but we did not find the same metabolisms in the serum, which may be because the serum or tissues, animal species, alcohol dose, and duration were different. In the present study, chronic alcohol consumption was elevated PG levels compared to the Con group about 1.3-fold, however, MWF (50, 100, and 200 mg/kg) or silymarin (200 mg/kg) supplementation were further increased PG levels by 1.5-, 2.2-, 1.6-, 1.6-fold, respectively, compared with the EtOH group.…”

“…Metabolomics provides a means of characterizing metabolic phenotypes and is used to identify metabolic disorders and discover biomarkers that can be used to diagnose or monitor diseases [15]. Ma et al [16] recently reported that 35 metabolites were significantly altered in the liver of alcohol diet compared to the isocaloric control diet mice. Dong et al [17] also demonstrated that chronic alcohol consumption induced significant alteration of serum FAs and bile acids by metabolic pathway analysis.…”

Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders

“…The NADPH produced by this pathway also serves as a reducing agent for anabolic pathways, such as fatty acid synthesis, and to regenerate reduced glutathione in response to oxidative stress [ 49 , 50 ]. Alcohol’s impact on the PPP is not well characterized, with suggestions that alcohol inhibits the PPP in non-pregnant alcoholics and in alcoholic liver disease [ 51 , 52 , 53 ]. The brain content of PPP intermediates is reduced in rats exposed to excessive alcohol drinking [ 54 ], suggesting that effects are conserved across organs.…”

Neurodevelopmental signatures of narcotic and neuropsychiatric risk factors in 3D human-derived forebrain organoids

“…The first, succinic acid, may be reflective of generalized alcohol exposure due to the formation of this metabolite during alcoholic fermentation [ 136 ], but is a relatively novel hit considering a lack of studies on the topic. The second, Guanosine Monophosphate Inosine, has been identified in a pathway analysis screening of metabolite dysfunction in an animal model of alcoholic liver disease [ 137 ] but otherwise also remains a novel hit. Further work on these two potential corollaries may therefore unveil their biological importance in mediating the effects of prenatal alcohol exposure on the developing brain.…”