Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver‐Related Events in Nonalcoholic Fatty Liver Disease

Wegermann, Kara; Howe, Christine L.; Henao, Ricardo; Wang, Ying; Guy, Cynthia D.; Abdelmalek, Manal F.; Diehl, Anna Mae; Moylan, Cynthia A.

doi:10.1002/hep4.1665

Cited by 23 publications

(19 citation statements)

References 42 publications

(49 reference statements)

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“…In NAFLD patients increased levels of 5-HIAA, the serotonin marker commonly used to screen for neuroendocrine tumors, were correlated with an increased risk for liver related complications such as ascites and hepatocellular carcinoma [88].…”

Section: Serotonin and Melatonin Pathwaysmentioning

confidence: 99%

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

2022

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and therefore is its burden of disease as NALFD is a risk factor for cirrhosis and is associated with other metabolic conditions such as type II diabetes, obesity, dyslipidaemia and atherosclerosis. Linking these cardiometabolic diseases is a state of low-grade inflammation, with higher cytokines and c-reactive protein levels found in individuals with NAFLD, obesity and type II diabetes. A possible therapeutic target to decrease this state of low-grade inflammation is the metabolism of the essential amino-acid tryptophan. Its three main metabolic pathways (kynurenine pathway, indole pathway and serotonin/melatonin pathway) result in metabolites such as kynurenic acid, xanturenic acid, indole-3-propionic acid and serotonin/melatonin. The kynurenine pathway is regulated by indoleamine 2,3-dioxygenase (IDO), an enzyme that is upregulated by pro-inflammatory molecules such as INF, IL-6 and LPS. Higher activity of IDO is associated with increased inflammation and fibrosis in NAFLD, as well with increased glucose levels, obesity and atherosclerosis. On the other hand, increased concentrations of the indole pathway metabolites, regulated by the gut microbiome, seem to result in more favorable outcomes. This narrative review summarizes the interactions between tryptophan metabolism, the gut microbiome and the immune system as potential drivers of cardiometabolic diseases in NAFLD.

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Section: Serotonin and Melatonin Pathwaysmentioning

confidence: 99%

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

2022

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“…A previous retrospective single-center cohort study, which included 187 participants, reported that vitamin E, primary bile acid and serotonin are associated with occurrence of future liver-related events [ 141 ]. A double blind randomized, and placebo-controlled trial was conducted previously whereby patients received three infusions containing vitamin E and the results showed significant improvement for ALT, AST and lactate dehydrogenase (LDH) levels after surgery [ 142 ].…”

Section: Metabolic Compartmentmentioning

confidence: 99%

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

Gao¹,

Qiu²,

Wang³

et al. 2022

Aging and disease

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Hepatic ischemia/reperfusion injury (IRI) is mainly characterized by high activation of immune inflammatory responses and metabolic responses. Understanding the molecular and metabolic mechanisms underlying development of hepatic IRI is critical for developing effective therapies for hepatic IRI. Recent advances in research have improved our understanding of the pathogenesis of IRI. During IRI, hepatocyte injury and inflammatory responses are mediated by crosstalk between the immune cells and metabolic components. This crosstalk can be targeted to treat or reverse hepatic IRI. Thus, a deep understanding of hepatic microenvironment, especially the immune and metabolic responses, can reveal new therapeutic opportunities for hepatic IRI. In this review, we describe important cells in the liver microenvironment (especially non-parenchymal cells) that regulate immune inflammatory responses. The role of metabolic components in the diagnosis and prevention of hepatic IRI are discussed. Furthermore, recent updated therapeutic strategies based on the hepatic microenvironment, including immune cells and metabolic components, are highlighted.

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“…[5,40] In the recent decade, extensive studies from animal models and human patients have found that NAFLD disease progression is closely associated with bile acid dysregulation and sphingolipid homeostasis. [48][49][50][51][52][53][54][55][56][57][58][59][60] Mechanisms linking bile acid metabolism to the development of NAFLD Consistently, clinical studies have demonstrated that primary and secondary CBAs are tightly associated with NAFLD progression and NASH severity. [30,48,49,51,52] A recent study reported that elevated hepatic taurochenodeoxycholic acid (TCDCA) and taurocholic acid (TCA) in NAFLD patients was associated with symptom onset, disease progression, or death.…”

Section: Bile Acids and Sphingolipids In Nafldmentioning

confidence: 99%

Bile acids and sphingolipids in non-alcoholic fatty liver disease

Jackson

Way

Zhou

2022

Chinese Medical Journal

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Non-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

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Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver‐Related Events in Nonalcoholic Fatty Liver Disease

Cited by 23 publications

References 42 publications

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

Bile acids and sphingolipids in non-alcoholic fatty liver disease

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