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Biomedicines
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NASH and Systemic Complications: From Basic to Clinical Research
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NASH and Systemic Complications: From Basic to Clinical Research

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 75724

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

Special Issue Editors

Prof. Dr. Ronit Shiri-Sverdlov

E-Mail Website
Guest Editor
NUTRIM, Department of Molecular Genetics, Maastricht University, Maastricht, The Netherlands
Interests: translational research related to inflammation and metabolic health
Special Issues, Collections and Topics in MDPI journals
Dr. Sabine Baumgartner

E-Mail Website
Guest Editor
Department of Nutrition and Movement Sciences, Maastricht University, Maastricht, The Netherlands
Interests: nutrition; NASH; lipid metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

To date, our sedentary lifestyle in combination with Western-type diets—i.e., a high intake of sugar- and fat-enriched meals—has led to an increased incidence of non-alcoholic fatty liver disease (NAFLD), both in adults and in children. NAFLD is known as the hepatic manifestation of the metabolic syndrome that encompasses a spectrum of liver diseases. Whereas most patients simply develop a fatty liver (steatosis), up to one-third are affected by nonalcoholic steatohepatitis (NASH). NASH is a chronic inflammatory condition of the liver that can further progress to fibrosis and cirrhosis, which may eventually lead to liver failure and death. Hence, NASH is considered an ongoing, global health threat. Currently, the gold standard for diagnosing NASH is a liver biopsy, which has several limitations, and therapeutic options to cure NASH do not yet exist. Therefore, there is an urgent need for a better understanding of the underlying pathophysiology of NASH.

This Special Issue supports new insights into basic and clinical research on NASH and its systemic complications. It will shed light on the pathophysiology, clinical problems, diagnostic methods, therapeutic approaches and lifestyle adaptations of NASH as well as on its systemic effects, including gastrointestinal, cardiovascular and neurological diseases, diabetes and cancer-related metabolic diseases. The overall aim of this Special Issue is to create awareness of the opportunities and challenges in translational NASH research, i.e., to explore possible answers that basic research can provide, and vice versa, to translate basic research questions to human situations. This Special Issue stimulates all junior and senior researchers and clinicians in the field of NAFLD/NASH, obesity, diabetes, cardiometabolics and cancer to share their novel findings and new ideas. Hence, our mission is to learn to understand the difficulties in finding those patients at risk of developing complicated NASH.

Prof. Dr. Ronit Shiri-Sverdlov
Dr. Yvonne Oligschläger
Guest Editors

Manuscript Submission Information

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Keywords

  • hepatic inflammation
  • lipid metabolism
  • overweight
  • obesity
  • metabolic syndrome
  • systemic complications

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Related Special Issue

Published Papers (13 papers)

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Editorial

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4 pages, 182 KiB  
Editorial
NASH and Systemic Complications: From Basic to Clinical Research
by Sabine Baumgartner and Ronit Shiri-Sverdlov
Biomedicines 2021, 9(12), 1913; https://doi.org/10.3390/biomedicines9121913 - 14 Dec 2021
Cited by 2 | Viewed by 2296
Abstract
Nonalcoholic fatty liver disease (NAFLD) is known as the hepatic manifestation of the metabolic syndrome, and while most patients develop simple steatosis, up to one-third can develop nonalcoholic steatohepatitis (NASH) [...] Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)

Research

Jump to: Editorial, Review

17 pages, 2494 KiB  
Article
Dulaglutide Alone and in Combination with Empagliflozin Attenuate Inflammatory Pathways and Microbiome Dysbiosis in a Non-Diabetic Mouse Model of NASH
by Katharina Luise Hupa-Breier, Janine Dywicki, Björn Hartleben, Freya Wellhöner, Benjamin Heidrich, Richard Taubert, Young-Seon Elisabeth Mederacke, Maren Lieber, Konstantinos Iordanidis, Michael P. Manns, Heiner Wedemeyer, Matthias Hardtke-Wolenski and Elmar Jaeckel
Biomedicines 2021, 9(4), 353; https://doi.org/10.3390/biomedicines9040353 - 30 Mar 2021
Cited by 30 | Viewed by 4399
Abstract
Dysregulation of glucose homeostasis plays a major role in the pathogenesis of non-alcoholic steatohepatitis (NASH) as it activates proinflammatory and profibrotic processes. Beneficial effects of antiglycemic treatments such as GLP-1 agonist or SGLT-2 inhibitor on NASH in patients with diabetes have already been [...] Read more.
Dysregulation of glucose homeostasis plays a major role in the pathogenesis of non-alcoholic steatohepatitis (NASH) as it activates proinflammatory and profibrotic processes. Beneficial effects of antiglycemic treatments such as GLP-1 agonist or SGLT-2 inhibitor on NASH in patients with diabetes have already been investigated. However, their effect on NASH in a non-diabetic setting remains unclear. With this aim, we investigated the effect of long-acting GLP1-agonist dulaglutide and SGLT-2 inhibitor empagliflozin and their combination in a non-diabetic mouse model of NASH. C57BL/6 mice received a high-fat-high-fructose (HFHC) diet with a surplus of cholesterol for 16 weeks. After 12 weeks of diet, mice were treated with either dulaglutide, empagliflozin or their combination. Dulaglutide alone and in combination with empagliflozin led to significant weight loss, improved glucose homeostasis and diminished anti-inflammatory and anti-fibrotic pathways. Combination of dulaglutide and empagliflozin further decreased MoMFLy6CHigh and CD4+Foxp3+ T cells. No beneficial effects for treatment with empagliflozin alone could be shown. While no effect of dulaglutide or its combination with empaglifozin on hepatic steatosis was evident, these data demonstrate distinct anti-inflammatory effects of dulaglutide and their combination with empagliflozin in a non-diabetic background, which could have important implications for further treatment of NASH. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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16 pages, 815 KiB  
Article
Non-Alcoholic Steatohepatitis Decreases Microsomal Liver Function in the Absence of Fibrosis
by Wim Verlinden, Eugénie Van Mieghem, Laura Depauw, Thomas Vanwolleghem, Luisa Vonghia, Jonas Weyler, Ann Driessen, Dirk Callens, Laurence Roosens, Eveline Dirinck, An Verrijken, Luc Van Gaal and Sven Francque
Biomedicines 2020, 8(12), 546; https://doi.org/10.3390/biomedicines8120546 - 27 Nov 2020
Cited by 2 | Viewed by 2350
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) is rising across the globe, with the presence of steatohepatitis leading to a more aggressive clinical course. Currently, the diagnosis of non-alcoholic steatohepatitis (NASH) is based on histology, though with the high prevalence of NAFLD, [...] Read more.
The incidence of non-alcoholic fatty liver disease (NAFLD) is rising across the globe, with the presence of steatohepatitis leading to a more aggressive clinical course. Currently, the diagnosis of non-alcoholic steatohepatitis (NASH) is based on histology, though with the high prevalence of NAFLD, a non-invasive method is needed. The 13C-aminopyrine breath test (ABT) evaluates the microsomal liver function and could be a potential candidate. We aimed to evaluate a potential change in liver function in NASH patients and to evaluate the diagnostic power of ABT to detect NASH. We performed a retrospective analysis on patients suspected of NAFLD who underwent a liver biopsy and ABT. 440 patients were included. ABT did not decrease in patients with isolated liver steatosis but decreased significantly in the presence of NASH without fibrosis and decreased even further with the presence of significant fibrosis. The predictive power of ABT as a single test for NASH was low but improved in combination with ALT and ultrasonographic steatosis. We conclude that microsomal liver function of patients with NASH is significantly decreased, even in the absence of fibrosis. The ABT is thus a valuable tool in assessing the presence of NASH; and could be used as a supplementary diagnostic tool in clinical practice. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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29 pages, 6732 KiB  
Article
Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH
by Mei-Ju Hsu, Isabel Karkossa, Ingo Schäfer, Madlen Christ, Hagen Kühne, Kristin Schubert, Ulrike E. Rolle-Kampczyk, Stefan Kalkhof, Sandra Nickel, Peter Seibel, Martin von Bergen and Bruno Christ
Biomedicines 2020, 8(9), 350; https://doi.org/10.3390/biomedicines8090350 - 14 Sep 2020
Cited by 26 | Viewed by 5819
Abstract
Mesenchymal stromal cell (MSC) transplantation ameliorated hepatic lipid load; tissue inflammation; and fibrosis in rodent animal models of non-alcoholic steatohepatitis (NASH) by as yet largely unknown mechanism(s). In a mouse model of NASH; we transplanted bone marrow-derived MSCs into the livers; which were [...] Read more.
Mesenchymal stromal cell (MSC) transplantation ameliorated hepatic lipid load; tissue inflammation; and fibrosis in rodent animal models of non-alcoholic steatohepatitis (NASH) by as yet largely unknown mechanism(s). In a mouse model of NASH; we transplanted bone marrow-derived MSCs into the livers; which were analyzed one week thereafter. Combined metabolomic and proteomic data were applied to weighted gene correlation network analysis (WGCNA) and subsequent identification of key drivers. Livers were analyzed histologically and biochemically. The mechanisms of MSC action on hepatocyte lipid accumulation were studied in co-cultures of hepatocytes and MSCs by quantitative image analysis and immunocytochemistry. WGCNA and key driver analysis revealed that NASH caused the impairment of central carbon; amino acid; and lipid metabolism associated with mitochondrial and peroxisomal dysfunction; which was reversed by MSC treatment. MSC improved hepatic lipid metabolism and tissue homeostasis. In co-cultures of hepatocytes and MSCs; the decrease of lipid load was associated with the transfer of mitochondria from the MSCs to the hepatocytes via tunneling nanotubes (TNTs). Hence; MSCs may ameliorate lipid load and tissue perturbance by the donation of mitochondria to the hepatocytes. Thereby; they may provide oxidative capacity for lipid breakdown and thus promote recovery from NASH-induced metabolic impairment and tissue injury. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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Review

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13 pages, 1202 KiB  
Review
Role of Leptin in Non-Alcoholic Fatty Liver Disease
by Carlos Jiménez-Cortegana, Alba García-Galey, Malika Tami, Pilar del Pino, Isabel Carmona, Soledad López, Gonzalo Alba and Víctor Sánchez-Margalet
Biomedicines 2021, 9(7), 762; https://doi.org/10.3390/biomedicines9070762 - 30 Jun 2021
Cited by 62 | Viewed by 5735
Abstract
Non-alcoholic fatty liver disease (NAFLD), which affects about a quarter of the global population, poses a substantial health and economic burden in all countries, yet there is no approved pharmacotherapy to treat this entity, nor well-established strategies for its diagnosis. Its prevalence has [...] Read more.
Non-alcoholic fatty liver disease (NAFLD), which affects about a quarter of the global population, poses a substantial health and economic burden in all countries, yet there is no approved pharmacotherapy to treat this entity, nor well-established strategies for its diagnosis. Its prevalence has been rapidly driven by increased physical inactivity, in addition to excessive calorie intake compared to energy expenditure, affecting both adults and children. The increase in the number of cases, together with the higher morbimortality that this disease entails with respect to the general population, makes NAFLD a serious public health problem. Closely related to the development of this disease, there is a hormone derived from adipocytes, leptin, which is involved in energy homeostasis and lipid metabolism. Numerous studies have verified the relationship between persistent hyperleptinemia and the development of steatosis, fibrinogenesis and liver carcinogenesis. Therefore, further studies of the role of leptin in the NAFLD spectrum could represent an advance in the management of this set of diseases. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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16 pages, 2691 KiB  
Review
The Synergy between Organ-on-a-Chip and Artificial Intelligence for the Study of NAFLD: From Basic Science to Clinical Research
by Francesco De Chiara, Ainhoa Ferret-Miñana and Javier Ramón-Azcón
Biomedicines 2021, 9(3), 248; https://doi.org/10.3390/biomedicines9030248 - 2 Mar 2021
Cited by 16 | Viewed by 5211
Abstract
Non-alcoholic fatty liver affects about 25% of global adult population. On the long-term, it is associated with extra-hepatic compliances, multiorgan failure, and death. Various invasive and non-invasive methods are employed for its diagnosis such as liver biopsies, CT scan, MRI, and numerous scoring [...] Read more.
Non-alcoholic fatty liver affects about 25% of global adult population. On the long-term, it is associated with extra-hepatic compliances, multiorgan failure, and death. Various invasive and non-invasive methods are employed for its diagnosis such as liver biopsies, CT scan, MRI, and numerous scoring systems. However, the lack of accuracy and reproducibility represents one of the biggest limitations of evaluating the effectiveness of drug candidates in clinical trials. Organ-on-chips (OOC) are emerging as a cost-effective tool to reproduce in vitro the main NAFLD’s pathogenic features for drug screening purposes. Those platforms have reached a high degree of complexity that generate an unprecedented amount of both structured and unstructured data that outpaced our capacity to analyze the results. The addition of artificial intelligence (AI) layer for data analysis and interpretation enables those platforms to reach their full potential. Furthermore, the use of them do not require any ethic and legal regulation. In this review, we discuss the synergy between OOC and AI as one of the most promising ways to unveil potential therapeutic targets as well as the complex mechanism(s) underlying NAFLD. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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17 pages, 1010 KiB  
Review
Natural Progression of Non-Alcoholic Steatohepatitis to Hepatocellular Carcinoma
by Daryl Ramai, Waqqas Tai, Michelle Rivera, Antonio Facciorusso, Nicola Tartaglia, Mario Pacilli, Antonio Ambrosi, Christian Cotsoglou and Rodolfo Sacco
Biomedicines 2021, 9(2), 184; https://doi.org/10.3390/biomedicines9020184 - 12 Feb 2021
Cited by 27 | Viewed by 6454
Abstract
Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing [...] Read more.
Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma (HCC). The progression of NASH to HCC was initially defined according to a two-hit model which involved the development of steatosis, followed by lipid peroxidation and inflammation. However, current research defines a “multi-hit” or “multi-parallel hit” model which synthesizes several contributing pathways involved in progressive fibrosis and oncogenesis. This perspective considers the effects of cellular, genetic, immunologic, metabolic, and endocrine pathways leading up to HCC which underscores the complexity of this condition. This article will provide an updated review of the pathogenic mechanisms leading from NASH to HCC as well as an exploration of the role of biomarkers and screening. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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21 pages, 636 KiB  
Review
Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis
by Julio Plaza-Díaz, Patricio Solis-Urra, Jerónimo Aragón-Vela, Fernando Rodríguez-Rodríguez, Jorge Olivares-Arancibia and Ana I. Álvarez-Mercado
Biomedicines 2021, 9(2), 145; https://doi.org/10.3390/biomedicines9020145 - 3 Feb 2021
Cited by 24 | Viewed by 6580
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation). Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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12 pages, 1374 KiB  
Review
Magnesium, Little Known But Possibly Relevant: A Link between NASH and Related Comorbidities
by Jorge Simón, Teresa Cardoso Delgado, Luis Alfonso Martinez-Cruz and Maria Luz Martínez-Chantar
Biomedicines 2021, 9(2), 125; https://doi.org/10.3390/biomedicines9020125 - 27 Jan 2021
Cited by 8 | Viewed by 5926
Abstract
Non-alcoholic steatohepatitis (NASH) is characterized by an abnormal hepatic lipid accumulation accompanied by a necro-inflammatory process and a fibrotic response. It comprises from 10% to 30% of cases of patients with non-alcoholic liver disease, which is a global health problem affecting around a [...] Read more.
Non-alcoholic steatohepatitis (NASH) is characterized by an abnormal hepatic lipid accumulation accompanied by a necro-inflammatory process and a fibrotic response. It comprises from 10% to 30% of cases of patients with non-alcoholic liver disease, which is a global health problem affecting around a quarter of the worldwide population. Nevertheless, the development of NASH is often surrounded by a pathological context with other comorbidities, such as cardiovascular diseases, obesity, insulin resistance or type 2 diabetes mellitus. Dietary imbalances are increasingly recognized as the root cause of these NASH-related comorbidities. In this context, a growing concern exists about whether magnesium consumption in the general population is sufficient. Hypomagnesemia is a hallmark of the aforementioned NASH comorbidities, and deficiencies in magnesium are also widely related to the triggering of complications that aggravate NASH or derived pathologies. Moreover, the supplementation of this cation has proved to reduce mortality from hepatic complications. In the present review, the role of magnesium in NASH and related comorbidities has been characterized, unraveling the relevance of maintaining the homeostasis of this cation for the correct functioning of the organism. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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13 pages, 1127 KiB  
Review
Extracellular Vesicles as Drivers of Non-Alcoholic Fatty Liver Disease: Small Particles with Big Impact
by David Højland Ipsen and Pernille Tveden-Nyborg
Biomedicines 2021, 9(1), 93; https://doi.org/10.3390/biomedicines9010093 - 19 Jan 2021
Cited by 16 | Viewed by 4526
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming the leading chronic liver disease, negatively affecting the lives of millions of patients worldwide. The complex pathogenesis involves crosstalk between multiple cellular networks, but how the intricate communication between these cells drives disease progression remains to [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is becoming the leading chronic liver disease, negatively affecting the lives of millions of patients worldwide. The complex pathogenesis involves crosstalk between multiple cellular networks, but how the intricate communication between these cells drives disease progression remains to be further elucidated. Furthermore, the disease is not limited to the liver and includes the reprogramming of distant cell populations in different organs. Extracellular vesicles (EVs) have gained increased attention as mediators of cellular communication. EVs carry specific cargos that can act as disease-specific signals both locally and systemically. Focusing on NAFLD advancing to steatohepatitis (NASH), this review provides an update on current experimental and clinical findings of the potential role of EVs in hepatic inflammation and fibrosis, the main contributors to progressive NASH. Particular attention is placed on the characteristics of EV cargos and potential specificity to disease stages, with putative value as disease markers and treatment targets for future investigations. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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21 pages, 6211 KiB  
Review
Usefulness of Different Imaging Modalities in Evaluation of Patients with Non-Alcoholic Fatty Liver Disease
by Karolina Grąt, Michał Grąt and Olgierd Rowiński
Biomedicines 2020, 8(9), 298; https://doi.org/10.3390/biomedicines8090298 - 21 Aug 2020
Cited by 18 | Viewed by 5208
Abstract
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are becoming some of the major health problems in well-developed countries, together with the increasing prevalence of obesity, metabolic syndrome, and all of their systemic complications. As the future prognoses are even more disturbing [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are becoming some of the major health problems in well-developed countries, together with the increasing prevalence of obesity, metabolic syndrome, and all of their systemic complications. As the future prognoses are even more disturbing and point toward further increase in population affected with NAFLD/NASH, there is an urgent need for widely available and reliable diagnostic methods. Consensus on a non-invasive, accurate diagnostic modality for the use in ongoing clinical trials is also required, particularly considering a current lack of any registered drug for the treatment of NAFLD/NASH. The aim of this narrative review was to present current information on methods used to assess liver steatosis and fibrosis. There are several imaging modalities for the assessment of hepatic steatosis ranging from simple density analysis by computed tomography or conventional B-mode ultrasound to magnetic resonance spectroscopy (MRS), magnetic resonance imaging proton density fat fraction (MRI-PDFF) or controlled attenuation parameter (CAP). Fibrosis stage can be assessed by magnetic resonance elastography (MRE) or different ultrasound-based techniques: transient elastography (TE), shear-wave elastography (SWE) and acoustic radiation force impulse (ARFI). Although all of these methods have been validated against liver biopsy as the reference standard and provided good accuracy, the MRS and MRI-PDFF currently outperform other methods in terms of diagnosis of steatosis, and MRE in terms of evaluation of fibrosis. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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16 pages, 590 KiB  
Review
Depression and Cognitive Impairment—Extrahepatic Manifestations of NAFLD and NASH
by Martina Colognesi, Daniela Gabbia and Sara De Martin
Biomedicines 2020, 8(7), 229; https://doi.org/10.3390/biomedicines8070229 - 21 Jul 2020
Cited by 71 | Viewed by 8301
Abstract
Non-alcoholic fatty liver disease (NAFLD) and its complication non-alcoholic steatohepatitis (NASH) are important causes of liver disease worldwide. Recently, a significant association between these hepatic diseases and different central nervous system (CNS) disorders has been observed in an increasing number of patients. NAFLD-related [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) and its complication non-alcoholic steatohepatitis (NASH) are important causes of liver disease worldwide. Recently, a significant association between these hepatic diseases and different central nervous system (CNS) disorders has been observed in an increasing number of patients. NAFLD-related CNS dysfunctions include cognitive impairment, hippocampal-dependent memory impairment, and mood imbalances (in particular, depression and anxiety). This review aims at summarizing the main correlations observed between NAFLD development and these CNS dysfunctions, focusing on the studies investigating the mechanism(s) involved in this association. Growing evidences point at cerebrovascular alteration, neuroinflammation, and brain insulin resistance as NAFLD/NASH-related CNS manifestations. Since the pharmacological options available for the management of these conditions are still limited, further studies are needed to unravel the mechanism(s) of NAFLD/NASH and their central manifestations and identify effective pharmacological targets. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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23 pages, 918 KiB  
Review
NAFLD Preclinical Models: More than a Handful, Less of a Concern?
by Yvonne Oligschlaeger and Ronit Shiri-Sverdlov
Biomedicines 2020, 8(2), 28; https://doi.org/10.3390/biomedicines8020028 - 8 Feb 2020
Cited by 50 | Viewed by 10832
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and/or hepatocellular carcinoma. Due to its increasing prevalence, NAFLD is currently a major public health concern. Although a wide variety of preclinical models [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and/or hepatocellular carcinoma. Due to its increasing prevalence, NAFLD is currently a major public health concern. Although a wide variety of preclinical models have contributed to better understanding the pathophysiology of NAFLD, it is not always obvious which model is best suitable for addressing a specific research question. This review provides insights into currently existing models, mainly focusing on murine models, which is of great importance to aid in the identification of novel therapeutic options for human NAFLD. Full article
(This article belongs to the Special Issue NASH and Systemic Complications: From Basic to Clinical Research)
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