RETRACTED: Acetylation of lactate dehydrogenase B drives NAFLD progression by impairing lactate clearance

Wang, Tongxin; Chen, Kai; Yao, Weilei; Zheng, Ruilong; He, Qiongyu; Xia, Jun; Li, Juan; Shao, Yafei; Zhang, Li; Huang, Lu; Xu, Mingming; Zheng, Zeqi; Pan, Dingyu; Li, Zhen; Huang, Feiruo

doi:10.1016/j.jhep.2020.11.028

Cited by 67 publications

(57 citation statements)

References 39 publications

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“…As a cytotoxic and mutagenic product, pyruvaldeheye is derived from increased glycolysis. Damaging roles of lactate and pyruvaldeheye in the liver have been described that they can trigger zinflammation, oxidative stress, mitochondrial impairment and cell death ( de Bari et al., 2019 ; Wang et al., 2021 ). Therefore, increased lactate and pyruvaldeheye could aggravate the liver damage in the layers, which might facilitate the development of FLHS.…”

Section: Discussionmentioning

confidence: 99%

Untargeted and targeted metabolomics profiling reveals the underlying pathogenesis and abnormal arachidonic acid metabolism in laying hens with fatty liver hemorrhagic syndrome

Meng

Liu

et al. 2021

Poultry Science

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As a metabolic disease, fatty liver hemorrhagic syndrome ( FLHS ) has become the major factor responsible for the noninfectious cause of mortality in laying hens, which lead to huge economic losses to poultry industry. However, the pathogenesis of FLHS remains unclear. The aim of present study was to identify novel liver metabolites associated with FLHS. Twenty healthy Chinese commercial Jing Fen laying hens aged 90 d were used in present study. After acclimatization for 2 wk, the hens were divided into 2 treatments (n = 10): control group (normal diet) and FLHS group (high-energy low-protein diet). The experiment lasted for 48 d, and the laying hens were killed for blood and liver sampling at the end of the experiment. Blood biochemical indicators and liver pathological changes were examined. Meanwhile, the changes in liver metabolic profile were investigated with the application of metabolomics approach. Significant increased levels of alanine aminotransferase, aspartate aminotransferase, low density lipoprotein, total cholesterol and triglycerides, decreased high density lipoprotein ( P < 0.01), and hepatic steatosis were observed in hens of FLHS group, which suggested FLHS was successfully established in this study. Distinct changes in metabolite patterns in liver between control and FLHS group were observed by partial least-squares discriminant analysis. In total, 42 liver metabolites including tyrosine, glutathione, carnitine, linoleic acid, uric acid, arachidonic acid ( ARA ), lactate and lysophosphatidylcholine (14: 0) were identified and considered to be related with pathogenesis of FLHS. Pathway analysis revealed that these metabolites were mainly involved in amino acid metabolism, fatty acid metabolism, ARA metabolism, glucose metabolism and glycerophospholipid metabolism. Furthermore, targeted metabolomics found that ARA metabolites such as prostaglandins and hydroxyeicosatetraenoic acids were significantly increased in FLHS group ( P < 0.05). In conclusion, our data showed that liver metabolites and ARA metabolism were linked to the pathophysiology of FLHS, which provided a basis for understanding the pathogenesis of FLHS in laying hens.

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Section: Discussionmentioning

confidence: 99%

Untargeted and targeted metabolomics profiling reveals the underlying pathogenesis and abnormal arachidonic acid metabolism in laying hens with fatty liver hemorrhagic syndrome

Meng

Liu

et al. 2021

Poultry Science

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“…Moreover, the activity, abundance and mRNA level of PDK2 and PDK4 are consistently increased, and positively related to plasma free fatty acid (FFA) concentrations ( Bajotto et al, 2006 ; Go et al, 2016 ). Consistently, in the NAFLD patients and obese mice, the serum pyruvate concentration and liver pyruvate content are significantly higher than those of the control group ( Fletcher et al, 2019 ; Wang et al, 2020 ; Shannon et al, 2021 ), though there is no evidence that it is caused by inactivity of PDC. A current study by Shannon et al (2021) revealed a contradictory result that in obese mice, the activity of PDC is enhanced accompanied by the reduced activity of PDK4 and enhanced activity of PDP2.…”

Section: Carbohydrate Metabolismmentioning

confidence: 79%

“…The production of lactate in fatty liver is significantly higher than normal ( Liu et al, 2018 ; Wang et al, 2020 ), which is another feature of WARBURG effect ( de la Cruz-López et al, 2019 ). P300/CBP-associated factor (PCAF)-mediated high acetylation level of LDH-B is one of the main causes in the accumulation of lactate in NAFLD.…”

Section: Carbohydrate Metabolismmentioning

confidence: 99%

Metabolic Changes of Hepatocytes in NAFLD

Tian

et al. 2021

Front. Physiol.

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Nonalcoholic fatty liver disease (NAFLD) is often accompanied by systemic metabolic disorders such as hyperglycemia, insulin resistance, and obesity. The relationship between NAFLD and systemic metabolic disorders has been well reviewed before, however, the metabolic changes that occur in hepatocyte itself have not been discussed. In NAFLD, many metabolic pathways have undergone significant changes in hepatocyte, such as enhanced glycolysis, gluconeogenesis, lactate production, tricarboxylic acid (TCA) cycle, and decreased ketone body production, mitochondrial respiration, and adenosine triphosphate (ATP) synthesis, which play a role in compensating or exacerbating disease progression, and there is close and complex interaction existed between these metabolic pathways. Among them, some metabolic pathways can be the potential therapeutic targets for NAFLD. A detailed summary of the metabolic characteristics of hepatocytes in the context of NAFLD helps us better understand the pathogenesis and outcomes of the disease.

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“…Evidence suggests that p300 is not only a histone acetyltransferase ( 94 ) but also a promising candidate histone lactyltransferase. In addition, p300 tends to be highly enriched at the promoters of pluripotency genes (Oct4, Sall4, and c-Myc) but not somatic genes such as Setbp1, collagen type I alpha 1 chain (Col1a1), and collagen type V alpha 1 chain (Col5a1) during reprogramming.…”

Section: Epigenetic Decisions: Lactate and Acetyl-coamentioning

confidence: 99%

Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects

et al. 2021

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Lactate is an end product of glycolysis. As a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule. We briefly summarize emerging concepts regarding lactate metabolism, such as the lactate shuttle, lactate homeostasis, and lactate-microenvironment interaction. Accumulating evidence indicates that lactate-mediated reprogramming of immune cells and enhancement of cellular plasticity contribute to establishing disease-specific immunity status. However, the mechanisms by which changes in lactate states influence the establishment of diverse functional adaptive states are largely uncharacterized. Posttranslational histone modifications create a code that functions as a key sensor of metabolism and are responsible for transducing metabolic changes into stable gene expression patterns. In this review, we describe the recent advances in a novel lactate-induced histone modification, histone lysine lactylation. These observations support the idea that epigenetic reprogramming-linked lactate input is related to disease state outputs, such as cancer progression and drug resistance.

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RETRACTED: Acetylation of lactate dehydrogenase B drives NAFLD progression by impairing lactate clearance

Cited by 67 publications

References 39 publications

Untargeted and targeted metabolomics profiling reveals the underlying pathogenesis and abnormal arachidonic acid metabolism in laying hens with fatty liver hemorrhagic syndrome

Untargeted and targeted metabolomics profiling reveals the underlying pathogenesis and abnormal arachidonic acid metabolism in laying hens with fatty liver hemorrhagic syndrome

Metabolic Changes of Hepatocytes in NAFLD

Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects

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