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Metabolites
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The Application of Imaging Technology in Studying Liver Metabolism
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The Application of Imaging Technology in Studying Liver Metabolism

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 16111

Special Issue Editors

Dr. Jeanine J Prompers

E-Mail Website
Guest Editor
High Field MRI group, Division of Imaging and Oncology, Utrecht University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
Interests: magnetic resonance imaging (MRI) and spectroscopy (MRS); metabolic imaging; metabolic syndrome; cancer; assessment of therapy response
Prof. Dr. Martin Krššák

E-Mail Website
Guest Editor
Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Wien, Austria
Interests: in vivo nuclear magnetic resonance spectroscopy; non-invasive assessment of glucose and lipid metabolism; type 2 Diabetes; insulin resistance; exercise physiology; quantitative MRI; skeletal muscle; liver; adipose tissue

Special Issue Information

Dear Colleagues,

Besides numerous other functions, the liver plays a key role in regulating energy substrate supply to other organs, by temporarily storing carbohydrates and lipids after a meal and releasing them in the post-absorptive state. However, in conditions related to the metabolic syndrome, such as non-alcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes, liver metabolic function is often compromised. During the last decade, great efforts have been made to characterize these metabolic disturbances in more detail using non-invasive imaging techniques. Opposed to an invasive liver biopsy, these non-invasive imaging techniques offer the opportunity for long-term disease monitoring and assessment of therapy response. Furthermore, quantitative dynamic methodology allows for the assessment of fluxes and energy utilization in resting or metabolically challenged conditions.

 

This Special Issue aims at gathering the most recent developments in imaging technology to study liver metabolism and applications thereof in various diseases. Contributions to this Special Issue, both in the form of original research and review articles, may include both clinical and pre-clinical studies. Specific areas include, but are not limited to, magnetic resonance imaging and spectroscopy, nuclear imaging, liver carbohydrate and lipid metabolism, energetics, mitochondrial function, NAFLD, insulin resistance, type 2 diabetes, response to therapy and lifestyle interventions.


Dr. Jeanine J Prompers
Prof. Dr. Martin Krššák
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

  • Non-invasive imaging
  • Metabolic syndrome
  • Non-alcoholic fatty liver disease
  • Liver carbohydrate and lipid metabolism
  • Liver energetics

Published Papers (7 papers)

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Research

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20 pages, 2271 KiB  
Article
Distribution and Associated Factors of Hepatic Iron—A Population-Based Imaging Study
by Lisa Maier, Ricarda von Krüchten, Roberto Lorbeer, Jule Filler, Johanna Nattenmüller, Barbara Thorand, Wolfgang Koenig, Wolfgang Rathmann, Fabian Bamberg, Christopher L. Schlett, Annette Peters and Susanne Rospleszcz
Metabolites 2021, 11(12), 871; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11120871 - 15 Dec 2021
Cited by 2 | Viewed by 2613
Abstract
Hepatic iron overload can cause severe organ damage; therefore, an early diagnosis and the identification of potential risk factors is crucial. We aimed to investigate the sex-specific distribution of hepatic iron content (HIC) in a population-based cohort and identify relevant associated factors from [...] Read more.
Hepatic iron overload can cause severe organ damage; therefore, an early diagnosis and the identification of potential risk factors is crucial. We aimed to investigate the sex-specific distribution of hepatic iron content (HIC) in a population-based cohort and identify relevant associated factors from a panel of markers. We analyzed N = 353 participants from a cross-sectional sample (KORA FF4) who underwent whole-body magnetic resonance imaging. HIC was assessed by single-voxel spectroscopy with a high-speed T2-corrected multi-echo technique. A large panel of markers, including anthropometric, genetic, and laboratory values, as well as behavioral risk factors were assessed. Relevant factors associated with HIC were identified by variable selection based on LASSO regression with bootstrap resampling. HIC in the study sample (mean age at examination: 56.0 years, 58.4% men) was significantly lower in women (mean ± SD: 39.2 ± 4.1 s−1) than in men (41.8 ± 4.7 s−1, p < 0.001). Relevant factors associated with HIC were HbA1c as well as prediabetes for men and visceral adipose tissue as well as age for women. Hepatic fat, alcohol consumption, and genetic risk score for iron levels were associated with HIC in both sexes. In conclusion, there are sex-specific associations of HIC with markers of body composition, glucose metabolism, and alcohol consumption. Full article
(This article belongs to the Special Issue The Application of Imaging Technology in Studying Liver Metabolism)
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15 pages, 2557 KiB  
Article
Maternal High-Fat Feeding Affects the Liver and Thymus Metabolic Axis in the Offspring and Some Effects Are Attenuated by Maternal Diet Normalization in a Minipig Model
by Federica La Rosa, Letizia Guiducci, Maria Angela Guzzardi, Andrea Cacciato Insilla, Silvia Burchielli, Maurizia Rossana Brunetto, Ferruccio Bonino, Daniela Campani and Patricia Iozzo
Metabolites 2021, 11(12), 800; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11120800 - 26 Nov 2021
Cited by 1 | Viewed by 1839
Abstract
Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their offspring, in minipigs. Offspring born to [...] Read more.
Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their offspring, in minipigs. Offspring born to high-fat (HFD) and normal diet (ND) fed mothers were studied at week 1 and months 1, 6, 12 of life. Liver and thymus glucose uptake (GU) was measured with positron emission tomography during hyperinsulinemic-isoglycemia. Histological analyses were performed to quantify liver steatosis, inflammation, and hepatic hematopoietic niches (HHN), and thymocyte size and density in a subset. The protocol was repeated after maternal-diet-normalization in the HFD group. At one week, HFDoff were characterized by hyperglycemia, hyperinsulinemia, severe insulin resistance (IR), and high liver and thymus GU, associating with thymocyte size and density, with elevated weight-gain, liver IR, and steatosis in the first 6 months of life. Maternal diet normalization reversed thymus and liver hypermetabolism, and increased HHN at one week. It also normalized systemic insulin-sensitivity and liver fat content at all ages. Instead, weight-gain excess, hyperglycemia, and hepatic IR were still observed at 1 month, i.e., end-lactation. We conclude that intra-uterine HFD exposure leads to time-changing metabolic and immune-correlated abnormalities. Maternal diet-normalization reversed most of the effects in the offspring. Full article
(This article belongs to the Special Issue The Application of Imaging Technology in Studying Liver Metabolism)
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12 pages, 4376 KiB  
Article
Lipid Profile and Hepatic Fat Content Measured by 1H MR Spectroscopy in Patients before and after Liver Transplantation
by Martin Burian, Milan Hajek, Petr Sedivy, Irena Mikova, Pavel Trunecka and Monika Dezortova
Metabolites 2021, 11(9), 625; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11090625 - 15 Sep 2021
Cited by 2 | Viewed by 1994
Abstract
Increased hepatic fat content (HFC) is a hallmark of non-alcoholic fatty liver (NAFL) disease, a common condition in liver transplant recipients. Proton MR spectroscopy (1H MRS) and MR imaging-based proton density fat fraction as the only diagnosis modality enable precise non-invasive [...] Read more.
Increased hepatic fat content (HFC) is a hallmark of non-alcoholic fatty liver (NAFL) disease, a common condition in liver transplant recipients. Proton MR spectroscopy (1H MRS) and MR imaging-based proton density fat fraction as the only diagnosis modality enable precise non-invasive measurement of HFC and, also, fatty acid profiles in vivo. Using 1H MRS at 3T, we examined 47 liver transplantation candidates and 101 liver graft recipients. A point-resolved spectroscopy sequence was used to calculate the steatosis grade along with the saturated, unsaturated and polyunsaturated fractions of fatty acids in the liver. The steatosis grade measured by MRS was compared with the histological steatosis grade. HFC, represented by fat fraction values, is adept at distinguishing non-alcoholic steatohepatitis (NASH), NAFL and non-steatotic liver transplant patients. Relative hepatic lipid saturation increases while unsaturation decreases in response to increased HFC. Additionally, relative hepatic lipid saturation increases while unsaturation and polyunsaturation both decrease in liver recipients with histologically proven post-transplant NASH or NAFL compared to non-steatotic patients. HFC, measured by in vivo 1H MRS, correlated well with histological results. 1H MRS is a simple and fast method for in vivo analysis of HFC and its composition. It provides non-invasive support for NAFL and NASH diagnoses. Full article
(This article belongs to the Special Issue The Application of Imaging Technology in Studying Liver Metabolism)
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Review

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17 pages, 1658 KiB  
Review
Magnetic Resonance Imaging and Spectroscopy Methods to Study Hepatic Glucose Metabolism and Their Applications in the Healthy and Diabetic Liver
by Ayhan Gursan and Jeanine J. Prompers
Metabolites 2022, 12(12), 1223; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo12121223 - 05 Dec 2022
Cited by 6 | Viewed by 1685
Abstract
The liver plays an important role in whole-body glucose homeostasis by taking up glucose from and releasing glucose into the blood circulation. In the postprandial state, excess glucose in the blood circulation is stored in hepatocytes as glycogen. In the postabsorptive state, the [...] Read more.
The liver plays an important role in whole-body glucose homeostasis by taking up glucose from and releasing glucose into the blood circulation. In the postprandial state, excess glucose in the blood circulation is stored in hepatocytes as glycogen. In the postabsorptive state, the liver produces glucose by breaking down glycogen and from noncarbohydrate precursors such as lactate. In metabolic diseases such as diabetes, these processes are dysregulated, resulting in abnormal blood glucose levels. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are noninvasive techniques that give unique insight into different aspects of glucose metabolism, such as glycogenesis, glycogenolysis, and gluconeogenesis, in the liver in vivo. Using these techniques, liver glucose metabolism has been studied in regard to a variety of interventions, such as fasting, meal intake, and exercise. Moreover, deviations from normal hepatic glucose metabolism have been investigated in both patients with type 1 and 2 diabetes, as well as the effects of antidiabetic medications. This review provides an overview of current MR techniques to measure hepatic glucose metabolism and the insights obtained by the application of these techniques in the healthy and diabetic liver. Full article
(This article belongs to the Special Issue The Application of Imaging Technology in Studying Liver Metabolism)
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19 pages, 2329 KiB  
Review
Hepatic Positron Emission Tomography: Applications in Metabolism, Haemodynamics and Cancer
by Miikka-Juhani Honka, Eleni Rebelos, Simona Malaspina and Pirjo Nuutila
Metabolites 2022, 12(4), 321; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo12040321 - 02 Apr 2022
Cited by 2 | Viewed by 2833
Abstract
Evaluating in vivo the metabolic rates of the human liver has been a challenge due to its unique perfusion system. Positron emission tomography (PET) represents the current gold standard for assessing non-invasively tissue metabolic rates in vivo. Here, we review the existing literature [...] Read more.
Evaluating in vivo the metabolic rates of the human liver has been a challenge due to its unique perfusion system. Positron emission tomography (PET) represents the current gold standard for assessing non-invasively tissue metabolic rates in vivo. Here, we review the existing literature on the assessment of hepatic metabolism, haemodynamics and cancer with PET. The tracer mainly used in metabolic studies has been [18F]2-fluoro-2-deoxy-D-glucose (18F-FDG). Its application not only enables the evaluation of hepatic glucose uptake in a variety of metabolic conditions and interventions, but based on the kinetics of 18F-FDG, endogenous glucose production can also be assessed. 14(R,S)-[18F]fluoro-6-thia-Heptadecanoic acid (18F-FTHA), 11C-Palmitate and 11C-Acetate have also been applied for the assessment of hepatic fatty acid uptake rates (18F-FTHA and 11C-Palmitate) and blood flow and oxidation (11C-Acetate). Oxygen-15 labelled water (15O-H2O) has been used for the quantification of hepatic perfusion. 18F-FDG is also the most common tracer used for hepatic cancer diagnostics, whereas 11C-Acetate has also shown some promising applications in imaging liver malignancies. The modelling approaches used to analyse PET data and also the challenges in utilizing PET in the assessment of hepatic metabolism are presented. Full article
(This article belongs to the Special Issue The Application of Imaging Technology in Studying Liver Metabolism)
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15 pages, 749 KiB  
Review
Non-Invasive Analysis of Human Liver Metabolism by Magnetic Resonance Spectroscopy
by John G. Jones
Metabolites 2021, 11(11), 751; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11110751 - 29 Oct 2021
Cited by 5 | Viewed by 2087
Abstract
The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform on the status of both hepatic and systemic metabolic diseases as [...] Read more.
The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform on the status of both hepatic and systemic metabolic diseases as well as the disposition of medications. As a tool to better understand liver metabolism in these settings, in vivo magnetic resonance spectroscopy (MRS) offers a non-invasive means of monitoring hepatic metabolic activity in real time both by direct observation of concentrations and dynamics of specific metabolites as well as by observation of their enrichment by stable isotope tracers. This review summarizes the applications and advances in human liver metabolic studies by in vivo MRS over the past 35 years and discusses future directions and opportunities that will be opened by the development of ultra-high field MR systems and by hyperpolarized stable isotope tracers. Full article
(This article belongs to the Special Issue The Application of Imaging Technology in Studying Liver Metabolism)
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14 pages, 2006 KiB  
Review
Probing Hepatic Glucose Metabolism via 13C NMR Spectroscopy in Perfused Livers—Applications to Drug Development
by Corin O. Miller and Jin Cao
Metabolites 2021, 11(11), 712; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11110712 - 20 Oct 2021
Cited by 1 | Viewed by 1950
Abstract
Despite being first published over 40 years ago, the combination of 13C nuclear magnetic resonance spectroscopy (NMR) and the isolated perfused liver preparation remains a unique and relevant approach in investigating the effects of pharmacological interventions on hepatic metabolism. The use of [...] Read more.
Despite being first published over 40 years ago, the combination of 13C nuclear magnetic resonance spectroscopy (NMR) and the isolated perfused liver preparation remains a unique and relevant approach in investigating the effects of pharmacological interventions on hepatic metabolism. The use of intact, perfused livers maintains many metabolic reactions at their respective rates in vivo, while the use of 13C-labelled substrates in combination with 13C NMR allows for a detailed study of specific pathways, as well as the design of robust assays which can be used to evaluate novel pharmacological agents. In this review article, we share some of the methods used to probe glucose metabolism, and highlight key findings and successes derived from the application of this specialized technique to the area of drug development for diabetes and related metabolic disorders. Full article
(This article belongs to the Special Issue The Application of Imaging Technology in Studying Liver Metabolism)
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