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Diet, Oxidative Stress and Liver Metabolism

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (25 May 2024) | Viewed by 23505

Special Issue Editors


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Guest Editor
Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy
Interests: metabolism; foods; oxidative stress; inflammation; metabolic diseases
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Biology, University of Naples Federico II, 80126 Naples, Italy
Interests: liver diseases; oxidative stress; mitochondria function

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Guest Editor
Department of Biology, University of Naples Federico II, 80126 Naples, Italy
Interests: nutrition; inflammation; oxidative stress; metabolic diseases, mitochondria function
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nutrition plays a crucial role in the prevention of chronic diseases, as most of them can be related to lifestyle factors. In particular, foods can affect cellular oxidative stress, which is a risk factor for various diseases. Oxidative stress is caused by an imbalance between the amount of reactive oxygen species and the body’s antioxidant capacity. In this oxidant/antioxidant balance, the diet plays a crucial role. Indeed, dietary nutrients can influence individuals’ total antioxidant capacity, modulating the degree of oxidative stress and affecting the incidence of diseases related to oxidation. Food components can impair the balance between anti- and pro-oxidant agents, causing the alteration of liver function. The liver plays a key role in the regulation of various processes, such as metabolism, secretion, storage and the clearance of endogenous and exogenous substances. The goal of this Special Issue is to assemble a collection of original research and review articles describing the role of foods as a link between cellular oxidative stress and liver metabolism. Manuscripts that investigate regulatory mechanisms and pathologies related to oxidative stress and hepatic metabolism, focused on the critical role of the foods or nutritional interventions, will be considered.

Dr. Gina Cavaliere
Dr. Maria Pina Mollica
Dr. Fabiano Cimmino
Guest Editors

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Keywords

  • nutrition
  • metabolism
  • diet
  • foods
  • oxidative stress
  • antioxidant
  • liver

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Published Papers (8 papers)

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Research

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17 pages, 11847 KiB  
Article
Hepatic Steatosis Can Be Partly Generated by the Gut Microbiota–Mitochondria Axis via 2-Oleoyl Glycerol and Reversed by a Combination of Soy Protein, Chia Oil, Curcumin and Nopal
by Mónica Sánchez-Tapia, Sandra Tobón-Cornejo, Lilia G. Noriega, Natalia Vázquez-Manjarrez, Diana Coutiño-Hernández, Omar Granados-Portillo, Berenice M. Román-Calleja, Astrid Ruíz-Margáin, Ricardo U. Macías-Rodríguez, Armando R. Tovar and Nimbe Torres
Nutrients 2024, 16(16), 2594; https://doi.org/10.3390/nu16162594 - 6 Aug 2024
Cited by 3 | Viewed by 2376
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health problem, and recent evidence indicates that gut microbiota plays a key role in its development. It is known that 2-oleoyl glycerol (2-OG) produced by the gut microbiota is associated with hepatic fibrosis, but [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health problem, and recent evidence indicates that gut microbiota plays a key role in its development. It is known that 2-oleoyl glycerol (2-OG) produced by the gut microbiota is associated with hepatic fibrosis, but it is not known whether this metabolite is involved in the development of hepatic steatosis. The aim of this study was to evaluate how a high-fat–sucrose diet (HFS) increases 2-OG production through gut microbiota dysbiosis and to identify whether this metabolite modifies hepatic lipogenesis and mitochondrial activity for the development of hepatic steatosis as well as whether a combination of functional foods can reverse this process. Wistar rats were fed the HFS diet for 7 months. At the end of the study, body composition, biochemical parameters, gut microbiota, protein abundance, lipogenic and antioxidant enzymes, hepatic 2-OG measurement, and mitochondrial function of the rats were evaluated. Also, the effect of the consumption of functional food with an HFS diet was assessed. In humans with MASLD, we analyzed gut microbiota and serum 2-OG. Consumption of the HFS diet in Wistar rats caused oxidative stress, hepatic steatosis, and gut microbiota dysbiosis, decreasing α-diversity and increased Blautia producta abundance, which increased 2-OG. This metabolite increased de novo lipogenesis through ChREBP and SREBP-1. 2-OG significantly increased mitochondrial dysfunction. The addition of functional foods to the diet modified the gut microbiota, reducing Blautia producta and 2-OG levels, leading to a decrease in body weight gain, body fat mass, serum glucose, insulin, cholesterol, triglycerides, fatty liver formation, and increased mitochondrial function. To use 2-OG as a biomarker, this metabolite was measured in healthy subjects or with MASLD, and it was observed that subjects with hepatic steatosis II and III had significantly higher 2-OG than healthy subjects, suggesting that the abundance of this circulating metabolite could be a predictor marker of hepatic steatosis. Full article
(This article belongs to the Special Issue Diet, Oxidative Stress and Liver Metabolism)
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11 pages, 612 KiB  
Article
Dysfunction of the Murine Liver with Aging and Its Improvement with the Continuous Consumption of Enterococcus faecalis EC-12
by Yuko Makioka-Itaya, Ryo Inoue and Takamitsu Tsukahara
Nutrients 2024, 16(13), 2031; https://doi.org/10.3390/nu16132031 - 26 Jun 2024
Viewed by 1698
Abstract
Chronic inflammation is involved in the development of age-related diseases. Given its persistence, controlling chronic inflammation is essential for preventing age-related diseases. In this study, we investigated the effects of Enterococcus faecalis EC-12 (EC-12), which has immunomodulatory and antioxidant effects, on liver gene [...] Read more.
Chronic inflammation is involved in the development of age-related diseases. Given its persistence, controlling chronic inflammation is essential for preventing age-related diseases. In this study, we investigated the effects of Enterococcus faecalis EC-12 (EC-12), which has immunomodulatory and antioxidant effects, on liver gene expression and aging phenomena in mice. Short-term EC-12 administration stimulated the expression of genes involved in lipid synthesis and metabolism in the liver. Furthermore, long-term EC-12 administration from 10 weeks to 1.5 years of age resulted in significant increases in blood interleukin (IL)-6 and IL-10 concentrations (both p < 0.05) and a significant decrease in the monocyte chemotactic protein-1 concentration (p < 0.05). These results indicated pathologic improvement, such as suppression of fat degeneration in the liver. These results suggest that continuous EC-12 intake from a young age can suppress liver function abnormalities, which is one of the aging phenomena in old age, and contribute to health in old age. Full article
(This article belongs to the Special Issue Diet, Oxidative Stress and Liver Metabolism)
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14 pages, 2869 KiB  
Article
Effects of NPY-2 Receptor Antagonists, Semaglutide, PYY3-36, and Empagliflozin on Early MASLD in Diet-Induced Obese Rats
by Simon Kloock, Niklas Haerting, Gloria Herzog, Marie Oertel, Niklas Geiger, Andreas Geier, Vasco Sequeira, Alexander Nickel, Michael Kohlhaas, Martin Fassnacht and Ulrich Dischinger
Nutrients 2024, 16(6), 904; https://doi.org/10.3390/nu16060904 - 21 Mar 2024
Cited by 3 | Viewed by 3451
Abstract
(1) Background: Modulators of the Neuropeptide Y (NPY) system are involved in energy metabolism, but the effect of NPY receptor antagonists on metabolic-dysfunction-associated steatotic liver disease (MASLD), a common obesity-related comorbidity, are largely unknown. In this study, we report on the effects of [...] Read more.
(1) Background: Modulators of the Neuropeptide Y (NPY) system are involved in energy metabolism, but the effect of NPY receptor antagonists on metabolic-dysfunction-associated steatotic liver disease (MASLD), a common obesity-related comorbidity, are largely unknown. In this study, we report on the effects of antagonists of the NPY-2 receptor (Y2R) in comparison with empagliflozin and semaglutide, substances that are known to be beneficial in MASLD. (2) Methods: Diet-induced obese (DIO) male Wistar rats were randomized into the following treatment groups: empagliflozin, semaglutide ± PYY3-36, the Y2R antagonists JNJ 31020028 and a food-restricted group, as well as a control group. After a treatment period of 8 weeks, livers were weighed and histologically evaluated. QrtPCR was performed to investigate liver inflammation and de novo lipogenesis (in liver and adipose tissue). Serum samples were analysed for metabolic parameters. (3) Results: Semaglutide + PYY3-36 led to significant weight loss, reduced liver steatosis (p = 0.05), and decreased inflammation, insulin resistance, and leptin levels. JNJ-31020028 prevented steatosis (p = 0.03) without significant weight loss. Hepatic downregulation of de novo lipogenesis-regulating genes (SREBP1 and MLXIPL) was observed in JNJ-31020028-treated rats (p ≤ 0.0001). Food restriction also resulted in significantly reduced weight, steatosis, and hepatic de novo lipogenesis. (4) Conclusions: Body weight reduction (e.g., by food restriction or drugs like semaglutide ± PYY3-36) is effective in improving liver steatosis in DIO rats. Remarkably, the body-weight-neutral Y2R antagonists may be effective in preventing liver steatosis through a reduction in de novo lipogenesis, making this drug class a candidate for the treatment of (early) MASLD. Full article
(This article belongs to the Special Issue Diet, Oxidative Stress and Liver Metabolism)
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12 pages, 676 KiB  
Article
Effect of Fish Oil Parenteral Emulsion Supplementation on Inflammatory Parameters after Esophagectomy
by Ana Suárez-Lledó Grande, Josep M. Llop Talaveron, Elisabet Leiva Badosa, Leandre Farran Teixido, Mónica Miró Martín, Jordi Bas Minguet, Sergio Navarro Velázquez, Gloria Creus Costas, Nuria Virgili Casas, Mónica Fernández Álvarez and María B. Badía Tahull
Nutrients 2024, 16(1), 40; https://doi.org/10.3390/nu16010040 - 21 Dec 2023
Cited by 3 | Viewed by 1833
Abstract
(Background) Esophagectomy (EPG) presents high morbidity and mortality. Omega-3 fatty acids (ω-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of ω-3FA administered parenterally after esophagectomy are scarce. This study proposes to investigate the effect of combining fish oil lipid emulsions (LE) [...] Read more.
(Background) Esophagectomy (EPG) presents high morbidity and mortality. Omega-3 fatty acids (ω-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of ω-3FA administered parenterally after esophagectomy are scarce. This study proposes to investigate the effect of combining fish oil lipid emulsions (LE) administered parenterally with enteral nutrition support. (Methods) Randomization was 1:1:1 in three groups: Group A received a LE mixture of 0.4 g/kg/day of fish oil and 0.4 g/kg/day of LCT/MCT 50:50, Group B received 0.8 g/kg/day of fish oil LE, and Group C received 0.8 g/kg/day of LCT/MCT 50:50. Variables were measured at recruitment time and day +1, +3, and +5. Inflammatory variables studied were Interlukin-6, C-reactive protein (CRP), tumoral necrosis factor-α (TNF-α), IL-10, IL-8 and CD25s. Safety, nutritional parameters and complications were analyzed. (Results) Administration of ω-3LE in the immediate postoperative period did not modulate the earlier inflammatory response. Statistically significant differences were found in IL-6 and CRP overall temporal evolution but were not found when studying the type of LE administered or in patients needing critical care. Administration of ω-3 resulted in safe and improved hypertriglyceridemia, depending on the dose. (Conclusions) ω-3FA has no impact on the early inflammatory postoperative response assessed for a short period but was safe. More studies for longer periods are needed. Full article
(This article belongs to the Special Issue Diet, Oxidative Stress and Liver Metabolism)
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29 pages, 4014 KiB  
Article
Potential Defence Mechanisms Triggered by Monosodium Glutamate Sub-Chronic Consumption in Two-Year-Old Wistar Rats
by Octavia-Laura Moldovan, Camil-Eugen Vari, Amelia Tero-Vescan, Ovidiu Simion Cotoi, Iuliu Gabriel Cocuz, Flaviu Alexandru Tabaran, Romelia Pop, Ibolya Fülöp, Rafael Florin Chis, Ioana-Andreea Lungu and Aura Rusu
Nutrients 2023, 15(20), 4436; https://doi.org/10.3390/nu15204436 - 19 Oct 2023
Cited by 2 | Viewed by 2953
Abstract
Monosodium glutamate (MSG) is the sodium salt of glutamic acid (GLA), used as a flavour enhancer. MSG is considered a controversial substance. It is incriminated in disturbing the antioxidant system, but also has beneficial effects, as GLA metabolism plays a crucial role in [...] Read more.
Monosodium glutamate (MSG) is the sodium salt of glutamic acid (GLA), used as a flavour enhancer. MSG is considered a controversial substance. It is incriminated in disturbing the antioxidant system, but also has beneficial effects, as GLA metabolism plays a crucial role in homeostasis. This study highlights which positive or negative aspects of MSG sub-chronic consumption are better reflected in subjects potentially affected by advanced age. Daily doses of MSG were administered to four groups of two-year-old Wistar rats for 90 days: (I) 185 mg/kg bw, (II) 1500 mg/kg bw, (III) 3000 mg/kg bw and (IV) 6000 mg/kg bw, compared to a MSG non-consumer group. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct and total bilirubin, total cholesterol, triglycerides, creatinine and urea levels were analysed; stomach, liver and kidney samples were subjected to histopathological analysis. Although, in most cases, there were no statistical differences, interesting aspects of the dose–effect relationship were observed. After MSG sub-chronic consumption, the positive aspects of GLA seem to be reflected better than the negative ones. The hormesis effect, with low-level reactive oxygen species’ protective effects and GLA metabolism, may represent the hypothesis of a potential defence mechanism triggered by MSG sub-chronic consumption in ageing rats. Full article
(This article belongs to the Special Issue Diet, Oxidative Stress and Liver Metabolism)
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17 pages, 18714 KiB  
Article
Eriodictyol Alleviated LPS/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K/AKT Signaling Pathway
by Xiaomei Zheng, Xinyan Wu, Qiqi Wen, Huaqiao Tang, Ling Zhao, Fei Shi, Yinglun Li, Zhongqiong Yin, Yuanfeng Zou, Xu Song, Lixia Li, Xinghong Zhao and Gang Ye
Nutrients 2023, 15(20), 4349; https://doi.org/10.3390/nu15204349 - 12 Oct 2023
Cited by 15 | Viewed by 2564
Abstract
Eriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular [...] Read more.
Eriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular biological mechanisms. A total of 47 targets were predicted for the treatment of ALI with eriodictyol, and the PI3K/AKT signaling pathway played a key role in the anti-ALI processing of this drug. The in vivo experiment showed that eriodictyol can effectively reduce liver function-related biochemical indicators such as ALT, AST, and AKP. Eriodictyol can also up-regulate the levels of SOD and GSH, and inhibit the release of IL-1β, IL-6, and TNF-α. Additionally, TUNEL staining, immunohistochemistry, and RT-PCR experiments showed that eriodictyol activated the PI3K/AKT pathway and decreased the expression of Bax, caspase3, and caspase8 while increasing the expression of Bcl-2 m-RNA. Finally, molecular docking experiments and molecular dynamics simulations confirmed the stable binding between eriodictyol and PI3K, AKT molecules. This study showed that eriodictyol can activate the PI3K/AKT signaling pathway to alleviate ALI-related oxidative stress and apoptosis. Full article
(This article belongs to the Special Issue Diet, Oxidative Stress and Liver Metabolism)
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20 pages, 8080 KiB  
Article
Hepatocyte Aquaporins AQP8 and AQP9 Are Engaged in the Hepatic Lipid and Glucose Metabolism Modulating the Inflammatory and Redox State in Milk-Supplemented Rats
by Giovanna Trinchese, Patrizia Gena, Fabiano Cimmino, Gina Cavaliere, Chiara Fogliano, Sabino Garra, Angela Catapano, Lidia Petrella, Silvia Di Chio, Bice Avallone, Giuseppe Calamita and Maria Pina Mollica
Nutrients 2023, 15(16), 3651; https://doi.org/10.3390/nu15163651 - 20 Aug 2023
Cited by 3 | Viewed by 2148
Abstract
Milk is an important source of nutrients and energy, but there are still many uncertainties regarding the health effects of milk and dairy products consumption. Milk from different species varies in physicochemical and nutritional properties. We previously showed that dietary supplements with different [...] Read more.
Milk is an important source of nutrients and energy, but there are still many uncertainties regarding the health effects of milk and dairy products consumption. Milk from different species varies in physicochemical and nutritional properties. We previously showed that dietary supplements with different milks in rats trigger significant differences in metabolic and inflammatory states, modulating mitochondrial functions in metabolically active organs such as the liver and skeletal muscle. Here, we have deepened the effects of isoenergetic supplementation of milk (82 kJ) from cow (CM), donkey (DM) or human (HM) on hepatic metabolism to understand the interlink between mitochondrial metabolic flexibility, lipid storage and redox state and to highlight the possible role of two hepatocyte aquaporins (AQPs) of metabolic relevance, AQP8 and AQP9, in this crosstalk. Compared with rats with no milk supplementation, DM- and HM-fed rats had reduced hepatic lipid content with enhanced mitochondrial function and decreased oxidative stress. A marked reduction in AQP8, a hydrogen peroxide channel, was seen in the liver mitochondria of DM-fed rats compared with HM-fed, CM-fed and control animals. DM-fed or HM-fed rats also showed reduced hepatic inflammatory markers and less collagen and Kupffer cells. CM-fed rats showed higher hepatic fat content and increased AQP9 and glycerol permeability. A role of liver AQP8 and AQP9 is suggested in the different metabolic profiles resulting from milk supplementation. Full article
(This article belongs to the Special Issue Diet, Oxidative Stress and Liver Metabolism)
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Review

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25 pages, 7878 KiB  
Review
Management of Metabolic-Associated Fatty Liver Disease/Metabolic Dysfunction-Associated Steatotic Liver Disease: From Medication Therapy to Nutritional Interventions
by Mohammad Beygi, Salma Ahi, Samaneh Zolghadri and Agata Stanek
Nutrients 2024, 16(14), 2220; https://doi.org/10.3390/nu16142220 - 11 Jul 2024
Cited by 13 | Viewed by 5110
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common long-lasting liver disease that affects millions of people around the world. It is best identified with a hepatic fat build-up that ultimately leads to inflammation and damage. The classification and nomenclature of NAFLD have long [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a common long-lasting liver disease that affects millions of people around the world. It is best identified with a hepatic fat build-up that ultimately leads to inflammation and damage. The classification and nomenclature of NAFLD have long been a controversial topic, until 2020 when a group of international experts recommended substituting NAFLD with MAFLD (metabolic dysfunction-associated FLD). MAFLD was then terminologically complemented in 2023 by altering it to MASLD, i.e., metabolic dysfunction-associated steatotic liver disease (MASLD). Both the MAFLD and the MASLD terminologies comprise the metabolic element of the disorder, as they offer diagnostic benchmarks that are embedded in the metabolic risk factors that underlie the disease. MASLD (as a multisystemic disease) provides a comprehensive definition that includes a larger population of patients who are at risk of liver morbidity and mortality, as well as adverse cardiovascular and diabetes outcomes. MASLD highlights metabolic risks in lean or normal weight individuals, a factor that has not been accentuated or discussed in previous guidelines. Novel antihyperglycemic agents, anti-hyperlipidemic drugs, lifestyle modifications, nutritional interventions, and exercise therapies have not been extensively studied in MAFLD and MASLD. Nutrition plays a vital role in managing both conditions, where centralizing on a diet rich in whole vegetables, fruits, foods, healthy fats, lean proteins, and specific nutrients (e.g., omega-3 fatty acids and fibers) can improve insulin resistance and reduce inflammation. Thus, it is essential to understand the role of nutrition in managing these conditions and to work with patients to develop an individualized plan for optimal health. This review discusses prevention strategies for NAFLD/MAFLD/MASLD management, with particular attention to nutrition and lifestyle correction. Full article
(This article belongs to the Special Issue Diet, Oxidative Stress and Liver Metabolism)
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