Metabolic Programming of Hepatic Organ Function

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 March 2024) | Viewed by 6066

Special Issue Editors


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Guest Editor
Clinic for Gastroenterology and Hepatology, University Hospital Cologne, Faculty of Medicine, University of Cologne, 50937 Cologne, Germany
Interests: NAFLD; metabolic programming; metabolic syndrome
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Guest Editor
Spanish National Research Council (CSIC), Instituto de Biología y Genética Molecular (IBGM), 47003 Valladolid, Spain
Interests: obesity; diabetes; cardiovascular disease; metabolic syndrome; endocrinology; insulin resistance; insulin clearance; metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The liver acts as the central regulator of energy homeostasis by orchestrating numerous metabolic processes, e.g., glycolysis, gluconeogenesis, and fatty acid metabolism. Disruption of liver development and maturation as a result of metabolic imbalance early in life may have long-lasting adverse metabolic consequences, rendering the liver more susceptible to chronic diseases in later life.

Accumulating clinical and experimental evidence demonstrates that detrimental early-life risk factors (e.g., maternal obesity) cause an altered genetic, hormonal, and metabolic micro-environment for the developing fetus and thereby adversely influence fetal growth and organ development. For example, infants of obese mothers are at an increased risk for poor neonatal outcomes, including congenital abnormalities, and are more susceptible to cardiometabolic disorders such as obesity, insulin resistance, hypertension, dyslipidemia later, or non-alcoholic fatty liver disease later in life. Experimental studies support the notion that the intrauterine and early-life metabolic environment interferes with developmental processes and thereby determines organ structure, function, and susceptibility to diseases in the offspring. This condition has been coined as the concept of developmental origins of health and diseases (DOHaD), also known as the fetal programming hypothesis.

While increasing evidence suggests that there is also a metabolic programming of hepatic organ function, the underlying mechanisms remain poorly understood.

This Special Issue aims to feature insights into ‘early-life‘ mechanisms involved in the development of hepatic diseases, since a better understanding of these mechanisms could provide new strategies for effective prevention, diagnostics, and treatment. 

The topics that this Special Issue will cover include, among others, metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD), genetic and epigenetic regulation of liver development, novel diagnostic and prognostic biomarkers, metabolomics, liver crosstalk with other tissues/organs such as adipose tissue or gut, immunometabolism, neuroendocrine mechanisms, hepatocyte-immune cell crosstalk, and developmental programming of glucose and the lipid metabolism.

Studies may use interventions such as dietary approaches or pharmacological treatment and -omics approaches. Both basic and clinical research are welcome.

This Special Issue will publish high-quality original research articles and review articles related to this issue, inspired by, but not limited to the aspects mentioned above.

Dr. Philipp Kasper
Dr. German Perdomo
Guest Editors

Manuscript Submission Information

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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

  • metabolism
  • liver
  • early-life environment
  • developmental programming
  • epigenetics
  • metabolic syndrome
  • obesity
  • metabolic-dysfunction-associated fatty liver disease

Related Special Issue

Published Papers (4 papers)

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Research

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15 pages, 5098 KiB  
Article
Short Working Memory Impairment Associated with Hippocampal Microglia Activation in Chronic Hepatic Encephalopathy
by Bilal El-Mansoury, Kamal Smimih, Abdelaati El Khiat, Ahmed Draoui, Abdelmohcine Aimrane, Redouane Chatoui, Abdesslam Ferssiwi, Abdelali Bitar, Halima Gamrani, Arumugam R. Jayakumar and Omar El Hiba
Metabolites 2024, 14(4), 193; https://doi.org/10.3390/metabo14040193 - 29 Mar 2024
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Abstract
Hepatic encephalopathy (HE) is a major neuropsychological condition that occursas a result of impaired liver function. It is frequently observed in patients with advanced liver disease or cirrhosis. Memory impairment is among the symptoms of HE; the pathophysiologic mechanism for this enervating condition [...] Read more.
Hepatic encephalopathy (HE) is a major neuropsychological condition that occursas a result of impaired liver function. It is frequently observed in patients with advanced liver disease or cirrhosis. Memory impairment is among the symptoms of HE; the pathophysiologic mechanism for this enervating condition remains unclear. However, it is possible that neuroinflammation may be involved, as recent studies have emphasized such phenomena. Therefore, the aim of the present study is to assess short working memory (SWM) and examine the involvement of microglia in a chronic model of HE. The study was carried out with male Wistar rats that were induced by repeated thioacetamide (TAA) administration (100 mg/kg i.p injection for 10 days). SWM function was assessed through Y-maze, T-Maze, and novel object recognition (NOR) tests, together with an immunofluorescence study of microglia activation within the hippocampal areas. Our data showed impaired SWM in TAA-treated rats that was associated with microglial activation in the three hippocampal regions, and which contributed to cognitive impairment. Full article
(This article belongs to the Special Issue Metabolic Programming of Hepatic Organ Function)
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15 pages, 3289 KiB  
Article
Metabolic Analysis of DFO-Resistant Huh7 Cells and Identification of Targets for Combination Therapy
by Koichi Fujisawa, Toshihiko Matsumoto, Naoki Yamamoto, Takahiro Yamasaki and Taro Takami
Metabolites 2023, 13(10), 1073; https://doi.org/10.3390/metabo13101073 - 12 Oct 2023
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Abstract
Hepatocellular carcinoma (HCC) is one of the most refractory cancers with a high rate of recurrence. Iron is an essential trace element, and iron chelation has garnered attention as a novel therapeutic strategy for cancer. Since intracellular metabolism is significantly altered by inhibiting [...] Read more.
Hepatocellular carcinoma (HCC) is one of the most refractory cancers with a high rate of recurrence. Iron is an essential trace element, and iron chelation has garnered attention as a novel therapeutic strategy for cancer. Since intracellular metabolism is significantly altered by inhibiting various proteins by iron chelation, we investigated combination anticancer therapy targeting metabolic changes that are forcibly modified by iron chelator administration. The deferoxamine (DFO)-resistant cell lines were established by gradually increasing the DFO concentration. Metabolomic analysis was conducted to evaluate the metabolic alterations induced by DFO administration, aiming to elucidate the resistance mechanism in DFO-resistant strains and identify potential novel therapeutic targets. Metabolom analysis of the DFO-resistant Huh7 cells revealed enhanced glycolysis and salvage cycle, alternations in glutamine metabolism, and accumulation of dipeptides. Huh7 cultured in the absence of glutamine showed enhanced sensitivity to DFO, and glutaminase inhibitor (CB839) showed a synergistic effect with DFO. Furthermore, the effect of DFO was enhanced by an autophagy inhibitor (chloroquine) in vitro. DFO-induced metabolic changes are specific targets for the development of efficient anticancer combinatorial therapies using DFO. These findings will be useful for the development of new cancer therapeutics in refractory liver cancer. Full article
(This article belongs to the Special Issue Metabolic Programming of Hepatic Organ Function)
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14 pages, 2749 KiB  
Article
Comparison of Hepatic Metabolite Profiles between Infant and Adult Male Mice Using 1H-NMR-Based Untargeted Metabolomics
by Doyoung Kwon, Wonho Lee, Sou Hyun Kim and Young-Suk Jung
Metabolites 2022, 12(10), 910; https://doi.org/10.3390/metabo12100910 - 27 Sep 2022
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Abstract
Although age-related characteristics of hepatic metabolism are reported, those in infants are not fully understood. In the present study, we performed untargeted metabolomic profiling of the livers of infant (3-week-old) and adult (9-week-old) male ICR mice using 1H-NMR spectroscopy and compared 35 [...] Read more.
Although age-related characteristics of hepatic metabolism are reported, those in infants are not fully understood. In the present study, we performed untargeted metabolomic profiling of the livers of infant (3-week-old) and adult (9-week-old) male ICR mice using 1H-NMR spectroscopy and compared 35 abundant hepatic metabolite concentrations between the two groups. The liver/body weight ratio did not differ between the two groups; however, serum glucose, blood urea nitrogen, total cholesterol, and triglyceride concentrations were lower in infants than in adults. Hepatic carbohydrate metabolites (glucose, maltose, and mannose) were higher, whereas amino acids (glutamine, leucine, methionine, phenylalanine, tyrosine, and valine) were lower in infant mice than in adult mice. The concentrations of ascorbate, betaine, sarcosine, and ethanolamine were higher, whereas those of taurine, inosine, and O-phosphocholine were lower in infant mice than in adult mice. The differences in liver metabolites between the two groups could be due to differences in their developmental stages and dietary sources (breast milk for infants and laboratory chow for adults). The above results provide insights into the hepatic metabolism in infants; however, the exact implications of the findings require further investigation. Full article
(This article belongs to the Special Issue Metabolic Programming of Hepatic Organ Function)
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Review

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25 pages, 1402 KiB  
Review
Metformin and the Liver: Unlocking the Full Therapeutic Potential
by Federica Perazza, Laura Leoni, Santo Colosimo, Alessandra Musio, Giulia Bocedi, Michela D’Avino, Giulio Agnelli, Alba Nicastri, Chiara Rossetti, Federica Sacilotto, Giulio Marchesini, Maria Letizia Petroni and Federico Ravaioli
Metabolites 2024, 14(4), 186; https://doi.org/10.3390/metabo14040186 - 25 Mar 2024
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Abstract
Metformin is a highly effective medication for managing type 2 diabetes mellitus. Recent studies have shown that it has significant therapeutic benefits in various organ systems, particularly the liver. Although the effects of metformin on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated [...] Read more.
Metformin is a highly effective medication for managing type 2 diabetes mellitus. Recent studies have shown that it has significant therapeutic benefits in various organ systems, particularly the liver. Although the effects of metformin on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are still being debated, it has positive effects on cirrhosis and anti-tumoral properties, which can help prevent the development of hepatocellular carcinoma. Furthermore, it has been proven to improve insulin resistance and dyslipidaemia, commonly associated with liver diseases. While more studies are needed to fully determine the safety and effectiveness of metformin use in liver diseases, the results are highly promising. Indeed, metformin has a terrific potential for extending its full therapeutic properties beyond its traditional use in managing diabetes. Full article
(This article belongs to the Special Issue Metabolic Programming of Hepatic Organ Function)
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