Metabolism and Metabolomics of Liver in Health and Disease

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Lipid Metabolism".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 81090

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors


E-Mail Website
Guest Editor
1. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
2. Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland
Interests: nuclear receptor superfamily; gene regulation and gene expression profiling; metabolic regulations; development; skin and wound healing; cancer; liver physiology; non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH); adipose tissue; muscle and exercise; gut; microbiota; inter-organ cross-talk; nutrition; nutrigenetics and nutrigenomics
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
INRA ToxAlim, UMR1331, 180 Chemin de Tournefeuille, BP93173, 31027 Toulouse CEDEX3, France
Interests: metabolism; lipidomic; nuclear receptor superfamily; gene regulation and gene expression profiling; metabolic regulations; liver physiology; non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH); microbiota; inter-organ cross-talk; toxicology; nutrition; endocrinology; nutrigenetics and nutrigenomics

Special Issue Information

Dear Colleagues,

In this Issue, we will explore the use of targeted and untargeted metabolome analysis to investigate liver function in health (physiology) and diseases such as viral hepatitis, alcoholic liver disease (ADL), non-alcoholic fatty liver diseases (NAFLD), drug-induced liver injury (DILI), and autoimmune liver diseases.

Our aim is to underscore, through research and review articles, the broad prospects of systems biology and metabolomics for a better understanding of liver function in basic research and possible clinical applications of drug discovery, toxicology, and biomarker identification.

Prof. Dr. Walter Wahli
Dr. Hervé Guillou
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Liver functions
  • Fatty liver
  • Liver diseases
  • Molecular mechanisms and biomarkers

Published Papers (13 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 811 KiB  
Article
Distinguishing NASH Histological Severity Using a Multiplatform Metabolomics Approach
by George N. Ioannou, G. A. Nagana Gowda, Danijel Djukovic and Daniel Raftery
Metabolites 2020, 10(4), 168; https://doi.org/10.3390/metabo10040168 - 24 Apr 2020
Cited by 26 | Viewed by 3846
Abstract
Nonalcoholic fatty liver disease (NAFLD) is categorized based on histological severity into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). We used a multiplatform metabolomics approach to identify metabolite markers and metabolic pathways that distinguish NAFL from early NASH and advanced NASH. We [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is categorized based on histological severity into nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). We used a multiplatform metabolomics approach to identify metabolite markers and metabolic pathways that distinguish NAFL from early NASH and advanced NASH. We analyzed fasting serum samples from 57 prospectively-recruited patients with histologically-proven NAFLD, including 12 with NAFL, 31 with early NASH and 14 with advanced NASH. Metabolite profiling was performed using a combination of liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy analyzed with multivariate statistical and pathway analysis tools. We targeted 237 metabolites of which 158 were quantified. Multivariate analysis uncovered metabolite profile clusters for patients with NAFL, early NASH, and advanced NASH. Also, multiple individual metabolites were associated with histological severity, most notably spermidine which was more than 2-fold lower in advanced fibrosis vs. early fibrosis, in advanced NASH vs. NAFL and in advanced NASH vs. early NASH, suggesting that spermidine exercises a protective effect against development of fibrosing NASH. Furthermore, the results also showed metabolic pathway perturbations between early-NASH and advanced-NASH. In conclusion, using a combination of two reliable analytical platforms (LC-MS and NMR spectroscopy) we identified individual metabolites, metabolite clusters and metabolic pathways that were significantly different between NAFL, early-NASH, and advanced-NASH. These differences provide mechanistic insights as well as potentially important metabolic biomarker candidates that may noninvasively distinguish patients with NAFL, early-NASH, and advanced-NASH. The associations of spermidine levels with less advanced histology merit further assessment of the potential protective effects of spermidine in NAFLD. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Figure 1

12 pages, 1509 KiB  
Article
Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS
by Vivaldy Prinville, Leanne Ohlund and Lekha Sleno
Metabolites 2020, 10(1), 26; https://doi.org/10.3390/metabo10010026 - 7 Jan 2020
Cited by 13 | Viewed by 5650
Abstract
Bile acids represent a large class of steroid acids synthesized in the liver and further metabolized by many bacterial and mammalian enzymes. Variations in bile acid levels can be used as a measure of liver function. There still exists, however, a need to [...] Read more.
Bile acids represent a large class of steroid acids synthesized in the liver and further metabolized by many bacterial and mammalian enzymes. Variations in bile acid levels can be used as a measure of liver function. There still exists, however, a need to study the variation of individual circulating bile acids in the context of hepatotoxity or liver disease. Acetaminophen (APAP), a drug commonly taken to relieve pain and decrease fever, is known to cause acute liver failure at high doses. We have developed a targeted liquid chromatography-tandem mass spectrometry method to monitor the effects of different doses of APAP on the bile acid plasma profile in a rat model. The analysis method was optimized to ensure chromatographic resolution of isomeric species using a mixture of 46 standard bile acids, and 14 isotopically-labeled internal standard (IS) compounds detected in multiple reaction monitoring (MRM) mode on a triple quadrupole mass spectrometer. Four doses of acetaminophen were studied, the highest of which shows signs of hepatotoxicity in rats. This targeted method revealed that high dose APAP has an important effect on bile acid profiles. Changes were seen in several unconjugated bile acids as well as glycine conjugates; however, no obvious changes were apparent for taurine-conjugated species. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Figure 1

20 pages, 2541 KiB  
Article
Proton NMR Enables the Absolute Quantification of Aqueous Metabolites and Lipid Classes in Unique Mouse Liver Samples
by Aurélien Amiel, Marie Tremblay-Franco, Roselyne Gautier, Simon Ducheix, Alexandra Montagner, Arnaud Polizzi, Laurent Debrauwer, Hervé Guillou, Justine Bertrand-Michel and Cécile Canlet
Metabolites 2020, 10(1), 9; https://doi.org/10.3390/metabo10010009 - 21 Dec 2019
Cited by 16 | Viewed by 6128
Abstract
Hepatic metabolites provide valuable information on the physiological state of an organism, and thus, they are monitored in many clinical situations. Typically, monitoring requires several analyses for each class of targeted metabolite, which is time consuming. The present study aimed to evaluate a [...] Read more.
Hepatic metabolites provide valuable information on the physiological state of an organism, and thus, they are monitored in many clinical situations. Typically, monitoring requires several analyses for each class of targeted metabolite, which is time consuming. The present study aimed to evaluate a proton nuclear magnetic resonance (1H-NMR) method for obtaining quantitative measurements of aqueous and lipidic metabolites. We optimized the extraction protocol, the standard samples, and the organic solvents for the absolute quantification of lipid species. To validate the method, we analyzed metabolic profiles in livers of mice fed three different diets. We compared our results with values obtained with conventional methods and found strong correlations. The 1H-NMR protocol enabled the absolute quantification of 29 aqueous metabolites and eight lipid classes. Results showed that mice fed a diet enriched in saturated fatty acids had higher levels of triglycerides, cholesterol ester, monounsaturated fatty acids, lactate, 3-hydroxy-butyrate, and alanine and lower levels of glucose, compared to mice fed a control diet. In conclusion, proton NMR provided a rapid overview of the main lipid classes (triglycerides, cholesterol, phospholipids, fatty acids) and the most abundant aqueous metabolites in liver. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Figure 1

15 pages, 2493 KiB  
Article
Acupuncture on ST36, CV4 and KI1 Suppresses the Progression of Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease in Mice
by Xiangjin Meng, Xin Guo, Jing Zhang, Junji Moriya, Junji Kobayashi, Reimon Yamaguchi and Sohsuke Yamada
Metabolites 2019, 9(12), 299; https://doi.org/10.3390/metabo9120299 - 9 Dec 2019
Cited by 17 | Viewed by 4247
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and its treatment remain a constant challenge. A number of clinical trials have shown that acupuncture treatment has beneficial effects for patients with NAFLD, but the molecular mechanisms [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and its treatment remain a constant challenge. A number of clinical trials have shown that acupuncture treatment has beneficial effects for patients with NAFLD, but the molecular mechanisms underlying its action are still largely unknown. In this study, we established a mouse model of NAFLD by administering a methionine- and choline-deficient (MCD) diet and selected three acupoints (ST36, CV4, and KI1) or nonacupoints (sham) for needling. We then investigated the effects of acupuncture treatment on the progression of NAFLD and the underlying mechanisms. After two weeks of acupuncture treatment, the liver in the needling-nonapcupoint group (NG) mice appeared pale and yellowish in color, while that in the needling-acupoint group (AG) showed a bright red color. Histologically, fewer lipid droplets and inflammatory foci were observed in the AG liver than in the NG liver. Furthermore, the expression of proinflammatory signaling factors was significantly downregulated in the AG liver. A lipid analysis showed that the levels of triglyceride (TG) and free fatty acid (FFA) were lower in the AG liver than in the NG liver, with an altered expression of lipid metabolism-related factors as well. Moreover, the numbers of 8-hydroxy-2′-deoxyguanosine (8-OHdG)-positive hepatocytes and levels of hepatic thiobarbituric acid reactive substances (TBARS) were significantly lower in AG mice than in NG mice. In line with these results, a higher expressions of antioxidant factors was found in the AG liver than in the NG liver. Our results indicate that acupuncture repressed the progression of NAFLD by inhibiting inflammatory reactions, reducing oxidative stress, and promoting lipid metabolism of hepatocytes, suggesting that this approach might be an important complementary treatment for NAFLD. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Figure 1

10 pages, 586 KiB  
Article
Exposure of HepaRG Cells to Sodium Saccharin Underpins the Importance of Including Non-Hepatotoxic Compounds When Investigating Toxicological Modes of Action Using Metabolomics
by Matthias Cuykx, Charlie Beirnaert, Robim Marcelino Rodrigues, Kris Laukens, Tamara Vanhaecke and Adrian Covaci
Metabolites 2019, 9(11), 265; https://doi.org/10.3390/metabo9110265 - 4 Nov 2019
Cited by 1 | Viewed by 2676
Abstract
Metabolites represent the most downstream information of the cellular organisation. Hence, metabolomics experiments are extremely valuable to unravel the endogenous pathways involved in a toxicological mode of action. However, every external stimulus can introduce alterations in the cell homeostasis, thereby obscuring the involved [...] Read more.
Metabolites represent the most downstream information of the cellular organisation. Hence, metabolomics experiments are extremely valuable to unravel the endogenous pathways involved in a toxicological mode of action. However, every external stimulus can introduce alterations in the cell homeostasis, thereby obscuring the involved endogenous pathways, biasing the interpretation of the results. Here we report on sodium saccharin, which is considered to be not hepatotoxic and therefore can serve as a reference compound to detect metabolic alterations that are not related to liver toxicity. Exposure of HepaRG cells to high levels of sodium saccharin (>10 mM) induced cell death, probably due to an increase in the osmotic pressure. Yet, a low number (n = 15) of significantly altered metabolites were also observed in the lipidome, including a slight decrease in phospholipids and an increase in triacylglycerols, upon daily exposure to 5 mM sodium saccharin for 72 h. The observation that a non-hepatotoxic compound can affect the metabolome underpins the importance of correct experimental design and data interpretation when investigating toxicological modes of action via metabolomics. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Figure 1

23 pages, 2172 KiB  
Article
A Lipidomic Analysis of Docosahexaenoic Acid (22:6, ω3) Mediated Attenuation of Western Diet Induced Nonalcoholic Steatohepatitis in Male Ldlr -/- Mice
by Manuel García-Jaramillo, Kelli A. Lytle, Melinda H. Spooner and Donald B. Jump
Metabolites 2019, 9(11), 252; https://doi.org/10.3390/metabo9110252 - 28 Oct 2019
Cited by 20 | Viewed by 5452
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD ranges in severity from benign steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and primary hepatocellular cancer (HCC). Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with NAFLD, and the [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD ranges in severity from benign steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and primary hepatocellular cancer (HCC). Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with NAFLD, and the western diet (WD) is a major contributor to the onset and progression of these chronic diseases. Our aim was to use a lipidomic approach to identify potential lipid mediators of diet-induced NASH. We previously used a preclinical mouse (low density lipoprotein receptor null mouse, Ldlr -/-) model to assess transcriptomic mechanisms linked to WD-induced NASH and docosahexaenoic acid (DHA, 22:6, ω3)-mediated remission of NASH. This report used livers from the previous study to carry out ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and high-performance liquid chromatography coupled with dynamic multi-reaction monitoring (HPLC-dMRM) to assess the impact of the WD and DHA on hepatic membrane lipid and oxylipin composition, respectively. Feeding mice the WD increased hepatic saturated and monounsaturated fatty acids and arachidonic acid (ARA, 20:4, ω6) in membrane lipids and suppressed ω3 polyunsaturated fatty acids (PUFA) in membrane lipids and ω3 PUFA-derived anti-inflammatory oxylipins. Supplementing the WD with DHA lowered hepatic ARA in membrane lipids and ARA-derived oxylipins and significantly increased hepatic DHA and its metabolites in membrane lipids, as well as C20–22 ω3 PUFA-derived oxylipins. NASH markers of inflammation and fibrosis were inversely associated with hepatic C20–22 ω3 PUFA-derived Cyp2C- and Cyp2J-generated anti-inflammatory oxylipins (false discovery rate adjusted p-value; q ≤ 0.026). Our findings suggest that dietary DHA promoted partial remission of WD-induced NASH, at least in part, by lowering hepatic pro-inflammatory oxylipins derived from ARA and increasing hepatic anti-inflammatory oxylipins derived from C20–22 ω3 PUFA. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Graphical abstract

13 pages, 2001 KiB  
Article
Hepatic Metabolic Derangements Triggered by Hyperthermia: An In Vitro Metabolomic Study
by Ana Margarida Araújo, Maria Enea, Félix Carvalho, Maria de Lourdes Bastos, Márcia Carvalho and Paula Guedes de Pinho
Metabolites 2019, 9(10), 228; https://doi.org/10.3390/metabo9100228 - 15 Oct 2019
Cited by 6 | Viewed by 2790
Abstract
Background and aims: Liver toxicity is a well-documented and potentially fatal adverse complication of hyperthermia. However, the impact of hyperthermia on the hepatic metabolome has hitherto not been investigated. Methods: In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to assess the [...] Read more.
Background and aims: Liver toxicity is a well-documented and potentially fatal adverse complication of hyperthermia. However, the impact of hyperthermia on the hepatic metabolome has hitherto not been investigated. Methods: In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to assess the in vitro metabolic response of primary mouse hepatocytes (PMH, n = 10) to a heat stress stimulus, i.e., after 24 h exposure to 40.5 °C. Metabolomic profiling of both intracellular metabolites and volatile metabolites in the extracellular medium of PMH was performed. Results: Multivariate analysis showed alterations in levels of 22 intra- and 59 extracellular metabolites, unveiling the capability of the metabolic pattern to discriminate cells exposed to heat stress from cells incubated at normothermic conditions (37 °C). Hyperthermia caused a considerable loss of cell viability that was accompanied by significant alterations in the tricarboxylic acid cycle, amino acids metabolism, urea cycle, glutamate metabolism, pentose phosphate pathway, and in the volatile signature associated with the lipid peroxidation process. Conclusion: These results provide novel insights into the mechanisms underlying hyperthermia-induced hepatocellular damage. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Graphical abstract

Review

Jump to: Research

34 pages, 1036 KiB  
Review
Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease
by Sandra Steensels, Jixuan Qiao and Baran A. Ersoy
Metabolites 2020, 10(7), 283; https://doi.org/10.3390/metabo10070283 - 9 Jul 2020
Cited by 28 | Viewed by 6009
Abstract
Obesity is the primary risk factor for the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the worldwide prevalence of which continues to increase dramatically. The liver plays a pivotal role in the maintenance of whole-body lipid and glucose homeostasis. This is mainly mediated [...] Read more.
Obesity is the primary risk factor for the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the worldwide prevalence of which continues to increase dramatically. The liver plays a pivotal role in the maintenance of whole-body lipid and glucose homeostasis. This is mainly mediated by the transcriptional activation of hepatic pathways that promote glucose and lipid production or utilization in response to the nutritional state of the body. However, in the setting of chronic excessive nutrition, the dysregulation of hepatic transcriptional machinery promotes lipid accumulation, inflammation, metabolic stress, and fibrosis, which culminate in NAFLD. In this review, we provide our current understanding of the transcription factors that have been linked to the pathogenesis and progression of NAFLD. Using publicly available transcriptomic data, we outline the altered activity of transcription factors among humans with NAFLD. By expanding this analysis to common experimental mouse models of NAFLD, we outline the relevance of mouse models to the human pathophysiology at the transcriptional level. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Graphical abstract

17 pages, 665 KiB  
Review
Important Considerations for Sample Collection in Metabolomics Studies with a Special Focus on Applications to Liver Functions
by Lorraine Smith, Joran Villaret-Cazadamont, Sandrine P. Claus, Cécile Canlet, Hervé Guillou, Nicolas J. Cabaton and Sandrine Ellero-Simatos
Metabolites 2020, 10(3), 104; https://doi.org/10.3390/metabo10030104 - 12 Mar 2020
Cited by 60 | Viewed by 6089
Abstract
Metabolomics has found numerous applications in the study of liver metabolism in health and disease. Metabolomics studies can be conducted in a variety of biological matrices ranging from easily accessible biofluids such as urine, blood or feces, to organs, tissues or even cells. [...] Read more.
Metabolomics has found numerous applications in the study of liver metabolism in health and disease. Metabolomics studies can be conducted in a variety of biological matrices ranging from easily accessible biofluids such as urine, blood or feces, to organs, tissues or even cells. Sample collection and storage are critical steps for which standard operating procedures must be followed. Inappropriate sample collection or storage can indeed result in high variability, interferences with instrumentation or degradation of metabolites. In this review, we will first highlight important general factors that should be considered when planning sample collection in the study design of metabolomic studies, such as nutritional status and circadian rhythm. Then, we will discuss in more detail the specific procedures that have been described for optimal pre-analytical handling of the most commonly used matrices (urine, blood, feces, tissues and cells). Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Figure 1

58 pages, 1598 KiB  
Review
Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy
by Diren Beyoğlu and Jeffrey R. Idle
Metabolites 2020, 10(2), 50; https://doi.org/10.3390/metabo10020050 - 28 Jan 2020
Cited by 53 | Viewed by 8287
Abstract
In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and [...] Read more.
In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and metabolomics. HCC arises against a background of inflammation, steatosis, and cirrhosis, due mainly to hepatic insults caused by alcohol abuse, hepatitis B and C virus infection, adiposity, and diabetes. Metabolomics offers an opportunity, without recourse to liver biopsy, to discover biomarkers for premalignant liver disease, thereby alerting the potential of impending HCC. We have reviewed metabolomic studies in alcoholic liver disease (ALD), cholestasis, fibrosis, cirrhosis, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Specificity was our major criterion in proposing clinical evaluation of indole-3-lactic acid, phenyllactic acid, N-lauroylglycine, decatrienoate, N-acetyltaurine for ALD, urinary sulfated bile acids for cholestasis, cervonoyl ethanolamide for fibrosis, 16α-hydroxyestrone for cirrhosis, and the pattern of acyl carnitines for NAFL and NASH. These examples derive from a large body of published metabolomic observations in various liver diseases in adults, adolescents, and children, together with animal models. Many other options have been tabulated. Metabolomic biomarkers for premalignant liver disease may help reduce the incidence of HCC. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Figure 1

14 pages, 2239 KiB  
Review
Glucose-6 Phosphate, a Central Hub for Liver Carbohydrate Metabolism
by Fabienne Rajas, Amandine Gautier-Stein and Gilles Mithieux
Metabolites 2019, 9(12), 282; https://doi.org/10.3390/metabo9120282 - 20 Nov 2019
Cited by 59 | Viewed by 19054
Abstract
Cells efficiently adjust their metabolism according to the abundance of nutrients and energy. The ability to switch cellular metabolism between anabolic and catabolic processes is critical for cell growth. Glucose-6 phosphate is the first intermediate of glucose metabolism and plays a central role [...] Read more.
Cells efficiently adjust their metabolism according to the abundance of nutrients and energy. The ability to switch cellular metabolism between anabolic and catabolic processes is critical for cell growth. Glucose-6 phosphate is the first intermediate of glucose metabolism and plays a central role in the energy metabolism of the liver. It acts as a hub to metabolically connect glycolysis, the pentose phosphate pathway, glycogen synthesis, de novo lipogenesis, and the hexosamine pathway. In this review, we describe the metabolic fate of glucose-6 phosphate in a healthy liver and the metabolic reprogramming occurring in two pathologies characterized by a deregulation of glucose homeostasis, namely type 2 diabetes, which is characterized by fasting hyperglycemia; and glycogen storage disease type I, where patients develop severe hypoglycemia during short fasting periods. In these two conditions, dysfunction of glucose metabolism results in non-alcoholic fatty liver disease, which may possibly lead to the development of hepatic tumors. Moreover, we also emphasize the role of the transcription factor carbohydrate response element-binding protein (ChREBP), known to link glucose and lipid metabolisms. In this regard, comparing these two metabolic diseases is a fruitful approach to better understand the key role of glucose-6 phosphate in liver metabolism in health and disease. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Graphical abstract

17 pages, 659 KiB  
Review
Nicotinamide and NAFLD: Is There Nothing New Under the Sun?
by Maria Guarino and Jean-François Dufour
Metabolites 2019, 9(9), 180; https://doi.org/10.3390/metabo9090180 - 10 Sep 2019
Cited by 16 | Viewed by 4390
Abstract
Nicotinamide adenine dinucleotide (NAD) has a critical role in cellular metabolism and energy homeostasis. Its importance has been established early with the discovery of NAD’s therapeutic role for pellagra. This review addresses some of the recent findings on NAD physiopathology and their effects [...] Read more.
Nicotinamide adenine dinucleotide (NAD) has a critical role in cellular metabolism and energy homeostasis. Its importance has been established early with the discovery of NAD’s therapeutic role for pellagra. This review addresses some of the recent findings on NAD physiopathology and their effects on nonalcoholic fatty liver disease (NAFLD) pathogenesis, which need to be considered in the search for a better therapeutic approach. Reduced NAD concentrations contribute to the dysmetabolic imbalance and consequently to the pathogenesis of NAFLD. In this perspective, the dietary supplementation or the pharmacological modulation of NAD levels appear to be an attractive strategy. These reviewed studies open the doors to growing interest in NAD metabolism for NAFLD diagnosis, prevention, and treatment. Future rigorous clinical studies in humans will be necessary to validate these preliminary but promising results. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Figure 1

0 pages, 1366 KiB  
Review
RETRACTED: The OMICs Window into Nonalcoholic Fatty Liver Disease (NAFLD)
by Lucia Carulli, Giulia Zanca, Filippo Schepis and Erica Villa
Metabolites 2019, 9(2), 25; https://doi.org/10.3390/metabo9020025 - 1 Feb 2019
Cited by 6 | Viewed by 4430 | Retraction
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common cause of hepatic abnormalities worldwide. Nonalcoholic steatohepatitis (NASH) is part of the spectrum of NAFLD and leads to progressive liver disease, such as cirrhosis and hepatocellular carcinoma. In NASH patient, fibrosis represents the major predictor [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is a common cause of hepatic abnormalities worldwide. Nonalcoholic steatohepatitis (NASH) is part of the spectrum of NAFLD and leads to progressive liver disease, such as cirrhosis and hepatocellular carcinoma. In NASH patient, fibrosis represents the major predictor of liver-related mortality; therefore, it is important to have an early and accurate diagnosis of NASH. The current gold standard for the diagnosis of NASH is still liver biopsy. The development of biomarkers able to predict disease severity, prognosis, as well as response to therapy without the need for a biopsy is the focus of most up-to-date genomic, transcriptomic, proteomic, and metabolomic research. In the future, patients might be diagnosed and treated according to their molecular signatures. In this short review, we discuss how information from genomics, proteomics, and metabolomics contribute to the understanding of NAFLD pathogenesis. Full article
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Show Figures

Figure 1

Back to TopTop