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Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 81318

Special Issue Editors

Dr. Mariapia Vairetti

E-Mail Website
Guest Editor
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
Interests: liver; NAFLD/NASH; farnesoid X receptor; oxidative stress; metalloproteinases; signal transduction
Special Issues, Collections and Topics in MDPI journals
Dr. Giuseppe Colucci

E-Mail Website
Guest Editor
Department of Medical and Surgical, Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
Interests: chronic hepatitis; NAFLD-NASH; immunopatholoy; liver fibrosis
Special Issues, Collections and Topics in MDPI journals
Dr. Andrea Ferrigno

E-Mail Website
Guest Editor
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
Interests: liver; ischemia/reperfusion; metabotropic glutamate receptor 5; inflammation; G protein-coupled receptors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nonalcoholic fatty liver disease (NAFLD) is among the most common liver diseases worldwide, affecting up to 20%–30% of the human population. NAFLD is usually associated with the metabolic syndrome that is characterized by increased abdominal fat, insulin resistance, high blood pressure, and high blood triglycerides. In about 10% of individuals, NAFLD progresses to steatohepatitis (NASH), with a long-term risk of cirrhosis and hepatocellular carcinoma, among the most important causes of liver transplantation in US with consequent relevant social and economic impact. Nonetheless, specific pharmacological targets and treatment have not been found yet, leaving important medical needs still to be met. The Special Issue, “Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH)”, of the International Journal of Molecular Sciences, will include a selection of original research papers and reviews on novel molecular and cellular targets to prevent and treat NAFLD. This Special Issue will also include an update on the management of liver steatosis, inflammation, and fibrosis.

Dr. Mariapia Vairetti
Dr. Giuseppe Colucci
Dr. Andrea Ferrigno
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • fatty liver
  • steatosis
  • steatohepatitis
  • inflammation
  • fibrosis
  • cytochines
  • chemokine receptors
  • insulin sensitizing drugs
  • farnesoid X receptor agonists
  • bile acids
  • oxidative stress
  • mitochondrial function
  • peroxisome proliferator-activated receptors (PPARs)

Published Papers (22 papers)

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Editorial

Jump to: Research, Review

4 pages, 185 KiB  
Editorial
Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0
by Mariapia Vairetti, Giuseppe Colucci and Andrea Ferrigno
Int. J. Mol. Sci. 2022, 23(14), 7894; https://doi.org/10.3390/ijms23147894 - 18 Jul 2022
Cited by 1 | Viewed by 1751
Abstract
Nonalcoholic fatty liver disease (NAFLD) is among the most common liver diseases worldwide, affecting up to 20–30% of the human population [...] Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)

Research

Jump to: Editorial, Review

11 pages, 4135 KiB  
Article
Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet
by Mayuko Ichimura-Shimizu, Shiro Watanabe, Yuka Kashirajima, Ami Nagatomo, Hitomi Wada, Koichi Tsuneyama and Katsuhisa Omagari
Int. J. Mol. Sci. 2022, 23(16), 9268; https://doi.org/10.3390/ijms23169268 - 17 Aug 2022
Cited by 6 | Viewed by 1925
Abstract
Background: Recently, we established a novel rodent model of nonalcoholic steatohepatitis (NASH) with advanced fibrosis induced by a high-fat and high-cholesterol (HFC) diet containing cholic acid (CA), which is known to cause hepatotoxicity. The present study aimed to elucidate the direct impact of [...] Read more.
Background: Recently, we established a novel rodent model of nonalcoholic steatohepatitis (NASH) with advanced fibrosis induced by a high-fat and high-cholesterol (HFC) diet containing cholic acid (CA), which is known to cause hepatotoxicity. The present study aimed to elucidate the direct impact of dietary CA on the progression of NASH induced by feeding the HFC diet. Methods: Nine-week-old male Sprague–Dawley rats were randomly assigned to receive a normal, HFC, or CA-supplemented (0.1%, 0.5% or 2.0%, w/w) HFC diet for 9 weeks. Results: Histopathological assessment revealed that the supplementation of CA dose-dependently aggravated hepatic steatosis, inflammation, and fibrosis, reaching stage 4 cirrhosis in the 2.0% CA diet group. In contrast, the rats that were fed the HFC diet without any added CA developed mild steatosis and inflammation without fibrosis. The hepatic cholesterol content and mRNA expression involved in inflammatory response and fibrogenesis was higher in a CA dose-dependent manner. The hepatic chenodeoxycholic acid levels were higher in 2.0% CA diet group than in the control, although hepatic levels of total bile acid and CA did not increase dose-dependently with CA intake. Conclusion: Adding CA to the HFC diet altered bile acid metabolism and inflammatory response and triggered the development of fibrosis in the rat liver. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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18 pages, 2484 KiB  
Article
MCD Diet Rat Model Induces Alterations in Zinc and Iron during NAFLD Progression from Steatosis to Steatohepatitis
by Giuseppina Palladini, Laura Giuseppina Di Pasqua, Marta Cagna, Anna Cleta Croce, Stefano Perlini, Barbara Mannucci, Antonella Profumo, Andrea Ferrigno and Mariapia Vairetti
Int. J. Mol. Sci. 2022, 23(12), 6817; https://doi.org/10.3390/ijms23126817 - 19 Jun 2022
Cited by 8 | Viewed by 2155
Abstract
We evaluate the effects of the methionine-choline-deficient (MCD) diet on serum and hepatic zinc (Zn) and iron (Fe) and their relationships with matrix metalloproteinases (MMPs) and their modulators (TIMPs and RECK) as well as hepatic fatty acids using male Wistar rats fed 2-, [...] Read more.
We evaluate the effects of the methionine-choline-deficient (MCD) diet on serum and hepatic zinc (Zn) and iron (Fe) and their relationships with matrix metalloproteinases (MMPs) and their modulators (TIMPs and RECK) as well as hepatic fatty acids using male Wistar rats fed 2-, 4- and 8-week MCD diets. Serum and hepatic Zn decrease after an 8-week MCD diet. Serum Fe increases after an 8-week MCD diet and the same occurs for hepatic Fe. An increase in hepatic MMP activity, associated with a decrease in RECK and TIMPs, is found in the MCD 8-week group. Liver Fe shows a positive correlation versus MMPs and RECK, and an inverse correlation versus TIMPs. A positive correlation is found comparing liver Zn with stearic, vaccenic and arachidonic acids, and an inverse correlation is found with linolenic and docosatetraenoic acids. An opposite trend is found between liver Fe versus these fatty acids. During NAFLD progression from steatosis to steatohepatitis, MCD rats exhibit an increase in Zn and a decrease in Fe levels both in serum and tissue associated with alterations in hepatic MMPs and their inhibitors, and fatty acids. The correlations detected between Zn and Fe versus extracellular matrix modulators and fatty acids support their potential role as therapeutic targets. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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17 pages, 2823 KiB  
Article
Maternal Pyrroloquinoline Quinone Supplementation Improves Offspring Liver Bioactive Lipid Profiles throughout the Lifespan and Protects against the Development of Adult NAFLD
by Ashok Mandala, Evgenia Dobrinskikh, Rachel C. Janssen, Oliver Fiehn, Angelo D’Alessandro, Jacob E. Friedman and Karen R. Jonscher
Int. J. Mol. Sci. 2022, 23(11), 6043; https://doi.org/10.3390/ijms23116043 - 27 May 2022
Cited by 3 | Viewed by 2737
Abstract
Maternal obesity and consumption of a high-fat diet significantly elevate risk for pediatric nonalcoholic fatty liver disease (NAFLD), affecting 10% of children in the US. Almost half of these children are diagnosed with nonalcoholic steatohepatitis (NASH), a leading etiology for liver transplant. Animal [...] Read more.
Maternal obesity and consumption of a high-fat diet significantly elevate risk for pediatric nonalcoholic fatty liver disease (NAFLD), affecting 10% of children in the US. Almost half of these children are diagnosed with nonalcoholic steatohepatitis (NASH), a leading etiology for liver transplant. Animal models show that signs of liver injury and perturbed lipid metabolism associated with NAFLD begin in utero; however, safe dietary therapeutics to blunt developmental programming of NAFLD are unavailable. Using a mouse model of maternal Western-style diet (WD), we previously showed that pyrroloquinoline quinone (PQQ), a potent dietary antioxidant, protected offspring of WD-fed dams from development of NAFLD and NASH. Here, we used untargeted mass spectrometry-based lipidomics to delineate lipotoxic effects of WD on offspring liver and identify lipid targets of PQQ. PQQ exposure during pregnancy altered hepatic lipid profiles of WD-exposed offspring, upregulating peroxisome proliferator-activated receptor (PPAR) α signaling and mitochondrial fatty acid oxidation to markedly attenuate triglyceride accumulation beginning in utero. Surprisingly, the abundance of very long-chain ceramides, important in promoting gut barrier and hepatic function, was significantly elevated in PQQ-treated offspring. PQQ exposure reduced the hepatic phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio in WD-fed offspring and improved glucose tolerance. Notably, levels of protective n − 3 polyunsaturated fatty acids (PUFAs) were elevated in offspring exposed to PQQ, beginning in utero, and the increase in n − 3 PUFAs persisted into adulthood. Our findings suggest that PQQ supplementation during gestation and lactation augments pathways involved in the biosynthesis of long-chain fatty acids and plays a unique role in modifying specific bioactive lipid species critical for protection against NAFLD risk in later life. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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19 pages, 4599 KiB  
Article
Soyasapogenol C from Fermented Soybean (Glycine Max) Acting as a Novel AMPK/PPARα Dual Activator Ameliorates Hepatic Steatosis: A Novel SANDA Methodology
by Radha Arulkumar, Hee Jin Jung, Sang Gyun Noh and Hae Young Chung
Int. J. Mol. Sci. 2022, 23(10), 5468; https://doi.org/10.3390/ijms23105468 - 13 May 2022
Cited by 3 | Viewed by 1800
Abstract
(1) Background: Soyasapogenol C (SSC), a derivative of soyasapogenol B (SSB), is specifically found high in many fermented soybean (Glycine max) products, including Cheonggukjang (in Korean). However, the biological activities for preventing and treating hepatic steatosis, and the precise underlying mechanisms [...] Read more.
(1) Background: Soyasapogenol C (SSC), a derivative of soyasapogenol B (SSB), is specifically found high in many fermented soybean (Glycine max) products, including Cheonggukjang (in Korean). However, the biological activities for preventing and treating hepatic steatosis, and the precise underlying mechanisms of SSC, remain to be explored. (2) Methods: A novel SANDA (structural screening, ADMET prediction, network pharmacology, docking validation, and activity evaluation) methodology was used to examine whether SSC exerts hepatoprotective effects in silico and in vitro. (3) Results: SSC had better ADMET characteristics and a higher binding affinity with predicted targets chosen from network pathway analysis than SSB. SSC induced the phosphorylation of AMP-activated protein kinase (AMPK) and stimulated the nuclear translocation of peroxisome proliferator-activated receptor alpha (PPARα), further enhancing PPAR response element (PPRE) binding activity in HepG2 cells. Concurrently, SSC significantly inhibited triglyceride accumulation, which was associated with the suppression of lipogenesis genes and the enhancement of fatty acid oxidation gene expression in HepG2 cells. (4) Conclusions: Soyasapogenol C, discovered using a novel SANDA methodology from fermented soybean, is a novel AMPK/PPARα dual activator that is effective against hepatic steatosis. Dietary supplementation with soyasapogenol C may prevent the development of hepatic steatosis and other diseases associated with fat accumulation in the liver. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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15 pages, 2209 KiB  
Article
The Beneficial Effects of Triterpenic Acid and Acteoside in an In Vitro Model of Nonalcoholic Steatohepatitis (NASH)
by Noel Salvoza, Chiara Bedin, Andrea Saccani, Claudio Tiribelli and Natalia Rosso
Int. J. Mol. Sci. 2022, 23(7), 3562; https://doi.org/10.3390/ijms23073562 - 24 Mar 2022
Cited by 8 | Viewed by 2824
Abstract
Triterpenic acid (TA) and acteoside (ACT), the major components of APPLIVER and ACTEOS, respectively, have been reported to exert hepatoprotective effects, but the molecular mechanisms remain elusive, particularly in the NAFLD/NASH context. We assessed their effects in our well-established in vitro model resembling [...] Read more.
Triterpenic acid (TA) and acteoside (ACT), the major components of APPLIVER and ACTEOS, respectively, have been reported to exert hepatoprotective effects, but the molecular mechanisms remain elusive, particularly in the NAFLD/NASH context. We assessed their effects in our well-established in vitro model resembling the pathophysiological mechanisms involved in NASH. Human hepatocytes and hepatic stellate cells were exposed to free fatty acids (FFA) alone or in combination with APPLIVER and ACTEOS as a mono- or co-culture. Steatosis, inflammation, generation of reactive oxygen species (ROS), and collagen deposition were determined. ACTEOS reduced both the TNF-α and ROS production, and, most importantly, attenuated collagen deposition elicited by the excess of FFA in the co-culture model. APPLIVER also showed inhibition of both TNF-α production and collagen deposition caused by FFA accumulation. The compounds alone did not induce any cellular effects. The present study showed the efficacy of APPLIVER and ACTEOS on pathophysiological mechanisms related to NASH. These in vitro data suggest that these compounds deserve further investigation for possible use in NASH treatment. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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14 pages, 3382 KiB  
Article
TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD
by Andrea Caddeo, Marta Anna Kowalik, Marina Serra, Massimiliano Runfola, Andrea Bacci, Simona Rapposelli, Amedeo Columbano and Andrea Perra
Int. J. Mol. Sci. 2021, 22(23), 13105; https://doi.org/10.3390/ijms222313105 - 3 Dec 2021
Cited by 22 | Viewed by 3786
Abstract
Activation of thyroid hormone receptor β (THRβ) has shown beneficial effects on metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of TG68, a novel THRβ agonist, on fatty liver accumulation and liver injury in mice fed a high-fat [...] Read more.
Activation of thyroid hormone receptor β (THRβ) has shown beneficial effects on metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of TG68, a novel THRβ agonist, on fatty liver accumulation and liver injury in mice fed a high-fat diet (HFD). C57BL/6 mice fed HFD for 17 or 18 weeks, a time when all mice developed massive steatohepatitis, were then given TG68 at a dose of 9.35 or 2.8 mg/kg for 2 or 3 weeks, respectively. As a reference compound, the same treatment was adopted using equimolar doses of MGL-3196, a selective THRβ agonist currently in clinical phase III. The results showed that treatment with TG68 led to a reduction in liver weight, hepatic steatosis, serum transaminases, and circulating triglycerides. qRT-PCR analyses demonstrated activation of THRβ, as confirmed by increased mRNA levels of Deiodinase-1 and Malic enzyme-1, and changes in lipid metabolism, as revealed by increased expression of Acyl-CoA Oxidase-1 and Carnitine palmitoyltransferase-1. The present results showed that this novel THRβ agonist exerts an anti-steatogenic effect coupled with amelioration of liver injury in the absence of extra-hepatic side effects, suggesting that TG68 may represent a useful tool for the treatment of NAFLD. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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Graphical abstract

16 pages, 1676 KiB  
Article
In a Prediabetic Model, Empagliflozin Improves Hepatic Lipid Metabolism Independently of Obesity and before Onset of Hyperglycemia
by Martina Hüttl, Irena Markova, Denisa Miklankova, Iveta Zapletalova, Martin Poruba, Martin Haluzik, Ivana Vaněčkova and Hana Malinska
Int. J. Mol. Sci. 2021, 22(21), 11513; https://doi.org/10.3390/ijms222111513 - 26 Oct 2021
Cited by 21 | Viewed by 3025
Abstract
Recent studies suggest that treatment with SGLT-2 inhibitors can reduce hepatic lipid storage and ameliorate non-alcoholic fatty liver disease (NAFLD) development beyond their glycemic benefits. However, the exact mechanism involved is still unclear. We investigated the hepatic metabolic effect of empagliflozin (10 mg/kg/day [...] Read more.
Recent studies suggest that treatment with SGLT-2 inhibitors can reduce hepatic lipid storage and ameliorate non-alcoholic fatty liver disease (NAFLD) development beyond their glycemic benefits. However, the exact mechanism involved is still unclear. We investigated the hepatic metabolic effect of empagliflozin (10 mg/kg/day for eight weeks) on the development of NAFLD and its complications using HHTg rats as a non-obese prediabetic rat model. Empagliflozin treatment reduced neutral triacylglycerols and lipotoxic diacylglycerols in the liver and was accompanied by significant changes in relative mRNA expression of lipogenic enzymes (Scd-1, Fas) and transcription factors (Srebp1, Pparγ). In addition, alterations in the gene expression of cytochrome P450 proteins, particularly Cyp2e1 and Cyp4a, together with increased Nrf2, contributed to the improvement of hepatic lipid metabolism after empagliflozin administration. Decreased circulating levels of fetuin-A improved lipid metabolism and attenuated insulin resistance in the liver and in peripheral tissues. Our results highlight the beneficial effect of empagliflozin on hepatic lipid metabolism and lipid accumulation independent of obesity, with the mechanisms understood to involve decreased lipogenesis, alterations in cytochrome P450 proteins, and decreased fetuin-A. These changes help to alleviate NAFLD symptoms in the early phase of the disease and before the onset of diabetes. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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10 pages, 2676 KiB  
Article
5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction
by Takaaki Hashimoto, Takaaki Sugihara, Tsutomu Kanda, Tomoaki Takata and Hajime Isomoto
Int. J. Mol. Sci. 2021, 22(21), 11405; https://doi.org/10.3390/ijms222111405 - 22 Oct 2021
Cited by 3 | Viewed by 2238
Abstract
Endoplasmic reticulum (ER) stress plays a pivotal role in the progression of steatohepatitis. 5-aminolevulinic acid (5-ALA), a precursor in the heme biosynthetic pathway, has recently been reported to induce heme oxygenase (HO)-1. HO-1 exerts important cytoprotective actions. In this study, we aimed to [...] Read more.
Endoplasmic reticulum (ER) stress plays a pivotal role in the progression of steatohepatitis. 5-aminolevulinic acid (5-ALA), a precursor in the heme biosynthetic pathway, has recently been reported to induce heme oxygenase (HO)-1. HO-1 exerts important cytoprotective actions. In this study, we aimed to explore the therapeutic potential of 5-ALA on palmitate-induced ER stress and lipoapoptosis. Huh-7 cells were treated with palmitic acid (PA) (800 μM) to induce steatosis for eight hours. Steatosis was evaluated by Lipi-green staining. 5-ALA (200 μM) was added with PA. The gene expression levels of the nuclear factor erythroid 2–related factor 2 (NRF2), HO-1, Glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), C/EBP homologous protein (CHOP), and B-cell lymphoma 2 (BCL-2) were evaluated by RT-PCR. Caspase-3/7 activity was evaluated by fluorescein active Caspase-3/7 staining. Cell death was evaluated by Annexin V/SYTOX green staining. PA significantly induced steatosis and increased GRP78 expression in Huh-7 cells. 5-ALA significantly induced HO-1 and decreased GRP78 expression. ATF6 was subsequently decreased. However, NRF2 and CHOP expression were not altered. Anti-apoptotic BCL-2 expression significantly increased, and Caspase 3/7 activity and cell death also decreased. 5-ALA has a therapeutic potential on hepatic steatosis by suppressing ER stress and lipoapoptosis by attenuating GRP78 via HO-1 induction. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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15 pages, 87729 KiB  
Article
Establishment of an Adult Medaka Fatty Liver Model by Administration of a Gubra-Amylin-Nonalcoholic Steatohepatitis Diet Containing High Levels of Palmitic Acid and Fructose
by Koichi Fujisawa, Taro Takami, Shoki Okubo, Yuto Nishimura, Yusaku Yamada, Keisuke Kondo, Toshihiko Matsumoto, Naoki Yamamoto and Isao Sakaida
Int. J. Mol. Sci. 2021, 22(18), 9931; https://doi.org/10.3390/ijms22189931 - 14 Sep 2021
Cited by 3 | Viewed by 2345
Abstract
Among lifestyle-related diseases, fatty liver is the most common liver disease. To date, mammalian models have been used to develop methods for inhibiting fatty liver progression; however, new, more efficient models are expected. This study investigated the creation of a new model to [...] Read more.
Among lifestyle-related diseases, fatty liver is the most common liver disease. To date, mammalian models have been used to develop methods for inhibiting fatty liver progression; however, new, more efficient models are expected. This study investigated the creation of a new model to produce fatty liver more efficiently than the high-fat diet medaka model that has been used to date. We compared the GAN (Gubra-Amylin nonalcoholic steatohepatitis) diet, which has been used in recent years to induce fatty liver in mice, and the high-fat diet (HFD). Following administration of the diets for three months, enlarged livers and pronounced fat accumulation was noted. The GAN group had large fat vacuoles and lesions, including ballooning, compared to the HFD group. The GAN group had a higher incidence of lesions. When fenofibrate was administered to the fatty liver model created via GAN administration and liver steatosis was assessed, a reduction in liver fat deposition was observed, and this model was shown to be useful in drug evaluations involving fatty liver. The medaka fatty liver model administered with GAN will be useful in future fatty liver research. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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16 pages, 4856 KiB  
Article
Losartan Prevents Hepatic Steatosis and Macrophage Polarization by Inhibiting HIF-1α in a Murine Model of NAFLD
by Cheng-Hui Wang, Hsuan-Miao Liu, Zi-Yu Chang, Tse-Hung Huang and Tzung-Yan Lee
Int. J. Mol. Sci. 2021, 22(15), 7841; https://doi.org/10.3390/ijms22157841 - 22 Jul 2021
Cited by 21 | Viewed by 3413
Abstract
Hypoxia and hepatosteatosis microenvironments are fundamental traits of nonalcoholic fatty liver disease (NAFLD). Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with NAFLD, whereas the route and regulation of lipid [...] Read more.
Hypoxia and hepatosteatosis microenvironments are fundamental traits of nonalcoholic fatty liver disease (NAFLD). Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with NAFLD, whereas the route and regulation of lipid droplets (LDs) and macrophage polarization related to systemic inflammation in NAFLD is unknown. Losartan is an angiotensin II receptor antagonist, that approved portal hypertension and related HIF-1α pathways in hepatic injury models. Here, we show that losartan in a murine model of NAFLD significantly decreased hepatic de novo lipogenesis (DNL) as well as suppressed lipid droplets (LDs), LD-associated proteins, perilipins (PLINs), and cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector (CIDE) family in liver and epididymal white adipose tissues (EWAT) of ob/ob mice. Obesity-mediated macrophage M1 activation was also required for HIF-1α expression in the liver and EWAT of ob/ob mice. Administration of losartan significantly diminishes obesity-enhanced macrophage M1 activation and suppresses hepatosteatosis. Moreover, HIF-1α-mediated mitochondrial dysfunction was reversed in ob/ob mice treated with losartan. Together, the regulation of HIF-1α controls LDs protein expression and macrophage polarization, which highlights a potential target for losartan in NAFLD. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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Review

Jump to: Editorial, Research

13 pages, 789 KiB  
Review
Gut Microbiota—A Future Therapeutic Target for People with Non-Alcoholic Fatty Liver Disease: A Systematic Review
by Roberta Forlano, Mathuri Sivakumar, Benjamin H. Mullish and Pinelopi Manousou
Int. J. Mol. Sci. 2022, 23(15), 8307; https://doi.org/10.3390/ijms23158307 - 27 Jul 2022
Cited by 10 | Viewed by 2798
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria play a crucial role in the pathogenesis and progression of liver damage in patients with NAFLD, it has been suggested that manipulating the microbiome may represent a therapeutical option. In this review, we summarise the latest evidence supporting the manipulation of the intestinal microbiome as a potential therapy for treating liver disease in patients with NAFLD. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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18 pages, 769 KiB  
Review
Smad3 Phospho-Isoform Signaling in Nonalcoholic Steatohepatitis
by Takashi Yamaguchi, Katsunori Yoshida, Miki Murata, Kanehiko Suwa, Koichi Tsuneyama, Koichi Matsuzaki and Makoto Naganuma
Int. J. Mol. Sci. 2022, 23(11), 6270; https://doi.org/10.3390/ijms23116270 - 3 Jun 2022
Cited by 5 | Viewed by 3243
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis with insulin resistance, oxidative stress, lipotoxicity, adipokine secretion by fat cells, endotoxins (lipopolysaccharides) released by gut microbiota, and endoplasmic reticulum stress. Together, these factors promote NAFLD progression from steatosis to nonalcoholic steatohepatitis (NASH), [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis with insulin resistance, oxidative stress, lipotoxicity, adipokine secretion by fat cells, endotoxins (lipopolysaccharides) released by gut microbiota, and endoplasmic reticulum stress. Together, these factors promote NAFLD progression from steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and eventually end-stage liver diseases in a proportion of cases. Hepatic fibrosis and carcinogenesis often progress together, sharing inflammatory pathways. However, NASH can lead to hepatocarcinogenesis with minimal inflammation or fibrosis. In such instances, insulin resistance, oxidative stress, and lipotoxicity can directly lead to liver carcinogenesis through genetic and epigenetic alterations. Transforming growth factor (TGF)-β signaling is implicated in hepatic fibrogenesis and carcinogenesis. TGF-β type I receptor (TβRI) and activated-Ras/c-Jun-N-terminal kinase (JNK) differentially phosphorylate the mediator Smad3 to create two phospho-isoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). TβRI/pSmad3C signaling terminates cell proliferation, while constitutive Ras activation and JNK-mediated pSmad3L promote hepatocyte proliferation and carcinogenesis. The pSmad3L signaling pathway also antagonizes cytostatic pSmad3C signaling. This review addresses TGF-β/Smad signaling in hepatic carcinogenesis complicating NASH. We also discuss Smad phospho-isoforms as biomarkers predicting HCC in NASH patients with or without cirrhosis. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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19 pages, 2086 KiB  
Review
Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis
by Marija Branković, Igor Jovanović, Marija Dukić, Tijana Radonjić, Svetlana Oprić, Slobodan Klašnja and Marija Zdravković
Int. J. Mol. Sci. 2022, 23(9), 5146; https://doi.org/10.3390/ijms23095146 - 5 May 2022
Cited by 24 | Viewed by 3315
Abstract
The emerging issues nowadays are non-alcoholic fatty liver disease (NAFLD) and its advanced stage non-alcoholic steatohepatitis (NASH), which further can be a predisposing factor for chronic liver complications, such as cirrhosis and/or development of hepatocellular carcinoma (HCC). Liver lipotoxicity can influence the accumulation [...] Read more.
The emerging issues nowadays are non-alcoholic fatty liver disease (NAFLD) and its advanced stage non-alcoholic steatohepatitis (NASH), which further can be a predisposing factor for chronic liver complications, such as cirrhosis and/or development of hepatocellular carcinoma (HCC). Liver lipotoxicity can influence the accumulation of reactive oxygen species (ROS), so oxidative stress is also crucial for the progression of NASH. Moreover, NASH is in strong connection with metabolic disorders, and supporting evidence shows that insulin resistance (IR) is in a close relation to NAFLD, as it is involved in the progression to NASH and further progression to hepatic fibrosis. The major issue is that, at the moment, NASH treatment is based on lifestyle changes only due to the fact that no approved therapeutic options are available. The development of new therapeutic strategies should be conducted towards the potential NAFLD and NASH treatment by the modulation of IR but also by dietary antioxidants. As it seems, NASH is going to be the leading indication for liver transplantation as a consequence of increased disease prevalence and the lack of approved treatment; thus, an effective solution is needed as soon as possible. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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15 pages, 1443 KiB  
Review
SGLT2 Inhibitors as the Most Promising Influencers on the Outcome of Non-Alcoholic Fatty Liver Disease
by Luigi Mirarchi, Simona Amodeo, Roberto Citarrella, Anna Licata, Maurizio Soresi and Lydia Giannitrapani
Int. J. Mol. Sci. 2022, 23(7), 3668; https://doi.org/10.3390/ijms23073668 - 27 Mar 2022
Cited by 13 | Viewed by 5563
Abstract
Non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease in the Western world, is a common hepatic manifestation of metabolic syndrome (MetS). A specific cure has not yet been identified, and its treatment is currently based on risk factor therapy. Given that [...] Read more.
Non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease in the Western world, is a common hepatic manifestation of metabolic syndrome (MetS). A specific cure has not yet been identified, and its treatment is currently based on risk factor therapy. Given that the initial accumulation of triglycerides in the liver parenchyma, in the presence of inflammatory processes, mitochondrial dysfunction, lipotoxicity, glucotoxicity, and oxidative stress, can evolve into non-alcoholic steatohepatitis (NASH). The main goal is to identify the factors contributing to this evolution because, once established, untreated NASH can progress through fibrosis to cirrhosis and, ultimately, be complicated by hepatocellular carcinoma (HCC). Several drugs have been tested in clinical trials for use as specific therapy for NAFLD; most of them are molecules used to cure type 2 diabetes mellitus (T2DM), which is one of the main risk factors for NAFLD. Among the most studied is pioglitazone, either alone or in combination with vitamin E, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors. Actually, the most promising category seems to be sodium-glucose cotransporter (SGLT2) inhibitors. Their action is carried out by inhibiting glucose reabsorption in the proximal renal tubule, leading to its increased excretion in urine and decreased levels in plasma. Experimental studies in animal models have suggested that SGLT2 inhibitors may have beneficial modulatory effects on NAFLD/NASH, and several trials in patients have proven their beneficial effects on liver enzymes, BMI, blood lipids, blood glucose, and insulin resistance in NAFLD patients, thus creating strong expectations for their possible use in preventing the evolution of liver damage in these patients. We will review the main pathogenetic mechanisms, diagnostic modalities, and recent therapies of NAFLD, with particular attention to the use of SGLT2 inhibitors. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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23 pages, 699 KiB  
Review
Natural Compounds for Counteracting Nonalcoholic Fatty Liver Disease (NAFLD): Advantages and Limitations of the Suggested Candidates
by Noel Salvoza, Pablo J. Giraudi, Claudio Tiribelli and Natalia Rosso
Int. J. Mol. Sci. 2022, 23(5), 2764; https://doi.org/10.3390/ijms23052764 - 2 Mar 2022
Cited by 25 | Viewed by 5064
Abstract
The booming prevalence of nonalcoholic fatty liver disease (NAFLD) in adults and children will threaten the health system in the upcoming years. The “multiple hit” hypothesis is the currently accepted explanation of the complex etiology and pathophysiology of the disease. Some of the [...] Read more.
The booming prevalence of nonalcoholic fatty liver disease (NAFLD) in adults and children will threaten the health system in the upcoming years. The “multiple hit” hypothesis is the currently accepted explanation of the complex etiology and pathophysiology of the disease. Some of the critical pathological events associated with the development of NAFLD are insulin resistance, steatosis, oxidative stress, inflammation, and fibrosis. Hence, attenuating these events may help prevent or delay the progression of NAFLD. Despite an increasing understanding of the mechanisms involved in NAFLD, no approved standard pharmacological treatment is available. The only currently recommended alternative relies on lifestyle modifications, including diet and physical activity. However, the lack of compliance is still hampering this approach. Thus, there is an evident need to characterize new therapeutic alternatives. Studies of food bioactive compounds became an attractive approach to overcome the reticence toward lifestyle changes. The present study aimed to review some of the reported compounds with beneficial properties in NAFLD; namely, coffee (and its components), tormentic acid, verbascoside, and silymarin. We provide details about their protective effects, their mechanism of action in ameliorating the critical pathological events involved in NAFLD, and their clinical applications. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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12 pages, 672 KiB  
Review
The Intestinal Barrier and Its Dysfunction in Patients with Metabolic Diseases and Non-Alcoholic Fatty Liver Disease
by Roberta Forlano, Benjamin H. Mullish, Lauren A. Roberts, Mark R. Thursz and Pinelopi Manousou
Int. J. Mol. Sci. 2022, 23(2), 662; https://doi.org/10.3390/ijms23020662 - 8 Jan 2022
Cited by 19 | Viewed by 3007
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut–liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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17 pages, 4140 KiB  
Review
The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease
by Branka Filipovic, Snezana Lukic, Dragana Mijac, Marija Marjanovic-Haljilji, Marko Vojnovic, Jelena Bogdanovic, Tijana Glisic, Natasa Filipovic, Jamal Al Kiswani, Aleksandra Djokovic, Suncica Kapor, Slobodan Kapor, Zoran Bukumiric and Ana Starcevic
Int. J. Mol. Sci. 2021, 22(24), 13219; https://doi.org/10.3390/ijms222413219 - 8 Dec 2021
Cited by 23 | Viewed by 6175
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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18 pages, 2145 KiB  
Review
New Therapeutic Targets for Hepatic Fibrosis in the Integrin Family, α8β1 and α11β1, Induced Specifically on Activated Stellate Cells
by Yasuyuki Yokosaki and Norihisa Nishimichi
Int. J. Mol. Sci. 2021, 22(23), 12794; https://doi.org/10.3390/ijms222312794 - 26 Nov 2021
Cited by 11 | Viewed by 3739
Abstract
A huge effort has been devoted to developing drugs targeting integrins over 30 years, because of the primary roles of integrins in the cell-matrix milieu. Five αv-containing integrins, in the 24 family members, have been a central target of fibrosis. Currently, a small [...] Read more.
A huge effort has been devoted to developing drugs targeting integrins over 30 years, because of the primary roles of integrins in the cell-matrix milieu. Five αv-containing integrins, in the 24 family members, have been a central target of fibrosis. Currently, a small molecule against αvβ1 is undergoing a clinical trial for NASH-associated fibrosis as a rare agent aiming at fibrogenesis. Latent TGFβ activation, a distinct talent of αv-integrins, has been intriguing as a therapeutic target. None of the αv-integrin inhibitors, however, has been in the clinical market. αv-integrins commonly recognize an Arg-Gly-Asp (RGD) sequence, and thus the pharmacophore of inhibitors for the 5-integrins is based on the same RGD structure. The RGD preference of the integrins, at the same time, dilutes ligand specificity, as the 5-integrins share ligands containing RGD sequence such as fibronectin. With the inherent little specificity in both drugs and targets, “disease specificity” has become less important for the inhibitors than blocking as many αv-integrins. In fact, an almighty inhibitor for αv-integrins, pan-αv, was in a clinical trial. On the contrary, approved integrin inhibitors are all specific to target integrins, which are expressed in a cell-type specific manner: αIIbβ3 on platelets, α4β1, α4β7 and αLβ2 on leukocytes. Herein, “disease specific” integrins would serve as attractive targets. α8β1 and α11β1 are selectively expressed in hepatic stellate cells (HSCs) and distinctively induced upon culture activation. The exceptional specificity to activated HSCs reflects a rather “pathology specific” nature of these new integrins. The monoclonal antibodies against α8β1 and α11β1 in preclinical examinations may illuminate the road to the first medical agents. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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14 pages, 1317 KiB  
Review
Effect of Microbiome on Non-Alcoholic Fatty Liver Disease and the Role of Probiotics, Prebiotics, and Biogenics
by Mayumi Nagashimada and Masao Honda
Int. J. Mol. Sci. 2021, 22(15), 8008; https://doi.org/10.3390/ijms22158008 - 27 Jul 2021
Cited by 19 | Viewed by 4628
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver cirrhosis and hepatocellular carcinoma. NAFLD is associated with metabolic disorders such as obesity, insulin resistance, dyslipidemia, steatohepatitis, and liver fibrosis. Liver-resident (Kupffer cells) and recruited macrophages contribute to low-grade chronic inflammation in [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver cirrhosis and hepatocellular carcinoma. NAFLD is associated with metabolic disorders such as obesity, insulin resistance, dyslipidemia, steatohepatitis, and liver fibrosis. Liver-resident (Kupffer cells) and recruited macrophages contribute to low-grade chronic inflammation in various tissues by modulating macrophage polarization, which is implicated in the pathogenesis of metabolic diseases. Abnormalities in the intestinal environment, such as the gut microbiota, metabolites, and immune system, are also involved in the pathogenesis and development of NAFLD. Hepatic macrophage activation is induced by the permeation of antigens, endotoxins, and other proinflammatory substances into the bloodstream as a result of increased intestinal permeability. Therefore, it is important to understand the role of the gut–liver axis in influencing macrophage activity, which is central to the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH). Not only probiotics but also biogenics (heat-killed lactic acid bacteria) are effective in ameliorating the progression of NASH. Here we review the effect of hepatic macrophages/Kupffer cells, other immune cells, intestinal permeability, and immunity on NAFLD and NASH and the impact of probiotics, prebiotics, and biogenesis on those diseases. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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19 pages, 727 KiB  
Review
Current Options and Future Directions for NAFLD and NASH Treatment
by Chunye Zhang and Ming Yang
Int. J. Mol. Sci. 2021, 22(14), 7571; https://doi.org/10.3390/ijms22147571 - 15 Jul 2021
Cited by 45 | Viewed by 10153
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although there are many undergoing clinical trials for NAFLD treatment, there is no currently approved [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although there are many undergoing clinical trials for NAFLD treatment, there is no currently approved treatment. NAFLD accounts as a major causing factor for the development of hepatocellular carcinoma (HCC), and its incidence rises accompanying the prevalence of obesity and diabetes. Reprogramming of antidiabetic and anti-obesity medicine is a major treatment option for NAFLD and NASH. Liver inflammation and cellular death, with or without fibrosis account for the progression of NAFLD to NASH. Therefore, molecules and signaling pathways involved in hepatic inflammation, fibrosis, and cell death are critically important targets for the therapy of NAFLD and NASH. In addition, the avoidance of aberrant infiltration of inflammatory cytokines by treating with CCR antagonists also provides a therapeutic option. Currently, there is an increasing number of pre-clinical and clinical trials undergoing to evaluate the effects of antidiabetic and anti-obesity drugs, antibiotics, pan-caspase inhibitors, CCR2/5 antagonists, and others on NAFLD, NASH, and liver fibrosis. Non-invasive serum diagnostic markers are developed for fulfilling the need of diagnostic testing in a large amount of NAFLD cases. Overall, a better understanding of the underlying mechanism of the pathogenesis of NAFLD is helpful to choose an optimized treatment. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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17 pages, 6850 KiB  
Review
Recent Progress in the Molecular Imaging of Nonalcoholic Fatty Liver Disease
by Olivia Wegrzyniak, Maria Rosestedt and Olof Eriksson
Int. J. Mol. Sci. 2021, 22(14), 7348; https://doi.org/10.3390/ijms22147348 - 8 Jul 2021
Cited by 5 | Viewed by 3313
Abstract
Pathological fibrosis of the liver is a landmark feature in chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Diagnosis and assessment of progress or treatment efficacy today requires biopsy of the liver, which is a challenge in, e.g., [...] Read more.
Pathological fibrosis of the liver is a landmark feature in chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Diagnosis and assessment of progress or treatment efficacy today requires biopsy of the liver, which is a challenge in, e.g., longitudinal interventional studies. Molecular imaging techniques such as positron emission tomography (PET) have the potential to enable minimally invasive assessment of liver fibrosis. This review will summarize and discuss the current status of the development of innovative imaging markers for processes relevant for fibrogenesis in liver, e.g., certain immune cells, activated fibroblasts, and collagen depositions. Full article
(This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH) 2.0)
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