Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)—A Condition Associated with Heightened Sympathetic Activation

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood. Compelling evidence from animal and human studies suggest that heightened activation of the sympathetic nervous system is a key contributor to the development of MAFLD. Indeed, common treatment strategies for metabolic diseases such as diet and exercise to induce weight loss have been shown to exert their beneficial effects at least in part through the associated sympathetic inhibition. Furthermore, pharmacological and device-based approaches to reduce sympathetic activation have been demonstrated to improve the metabolic alterations frequently present in patients with obesity, MetSand diabetes. Currently available evidence, while still limited, suggests that sympathetic activation is of specific relevance in the pathogenesis of MAFLD and consequentially may offer an attractive therapeutic target to attenuate the adverse outcomes associated with MAFLD.

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Metabolic dysfunction-associated fatty liver disease increases risk of adverse outcomes in patients with chronic hepatitis B

JHEP Reports ◽

10.1016/j.jhepr.2021.100350 ◽

2021 ◽

pp. 100350

Author(s):

Laurens A. van Kleef ◽

Hannah S.J. Choi ◽

Willem P. Brouwer ◽

Bettina E. Hansen ◽

Keyur Patel ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Disease ◽

Hepatitis B ◽

Fatty Liver ◽

Chronic Hepatitis B ◽

Fatty Liver Disease ◽

Adverse Outcomes ◽

Metabolic Dysfunction

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Outcomes of NAFLD and MAFLD: Results from a community-based, prospective cohort study

PLoS ONE ◽

10.1371/journal.pone.0245762 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0245762 ◽

Cited By ~ 2

Author(s):

Madunil Anuk Niriella ◽

Dileepa Senajith Ediriweera ◽

Anuradhani Kasturiratne ◽

Shamila Thivanshi De Silva ◽

Anuradha Supun Dassanayaka ◽

...

Keyword(s):

Cohort Study ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Adverse Outcomes ◽

Metabolic Dysfunction ◽

Community Based ◽

Alcoholic Fatty Liver ◽

Metabolic Traits ◽

New Onset

Background The term “metabolic (dysfunction)-associated fatty liver disease” (MAFLD) is suggested alternative for “non-alcoholic fatty liver disease” (NAFLD), as it better reflects metabolic dysfunction. No study has compared outcomes of the two diagnostic criteria. Methods In an ongoing, community-based, cohort-study in suburban Sri Lanka, participants were randomly selected in 2007. They were reassessed in 2014 to evaluate new-onset metabolic traits (MTs) and cardiovascular-events (CVEs). Baseline characteristics, MTs and CVEs after 7-years were compared in NAFLD and MAFLD and vs. controls. Similarly, we compared these parameters in those excluded by the NAFLD definition but captured by the MAFLD definition and vice versa, and vs. controls. Findings Of 2985 recruited in 2007, 940 (31.5%) had NAFLD, 990 (33.1%) had MAFLD and 362 (12.1%) were controls. When compared to NAFLD, MAFLD captured an additional 2.9% and lost 1.3% individuals. At baseline, anthropometric and metabolic traits were similar in NAFLD and MAFLD. At follow-up in 7-years, the risk of having new-onset MTs and fatal/non-fatal CVEs were similar in the groups, but were significantly higher compared to controls. Those excluded by the NAFLD definition but captured by the MAFLD definition showed higher baseline MTs compared to those excluded by the MAFLD definition but captured by the NAFLD definition, and had substantially higher risk for having new-onset MTs and CVEs compared to controls. Interpretation Although NAFLD and MAFLD had similar MTs at baseline, and similar outcomes after 7-years, those who were excluded by the NAFLD definition but captured by the MAFLD definition seem at higher risk of adverse outcomes than those excluded by the MAFLD definition but captured by the NAFLD definition. Although the increase in the index population was small, redefining NAFLD as MAFLD seemed to improve clinical utility.

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Adlay Seed (Coix lacryma-jobi L.) Extracts Exhibit a Prophylactic Effect on Diet-Induced Metabolic Dysfunction and Nonalcoholic Fatty Liver Disease in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9519625 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Hao Chiang ◽

Hsu-Feng Lu ◽

Jui-Chieh Chen ◽

Yu-Hsin Chen ◽

Hsi-Tai Sun ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Metabolic Diseases ◽

Cell Model ◽

Metabolic Dysfunction ◽

Nonalcoholic Fatty Liver ◽

Global Issue ◽

Liver Cell Model

Nonalcoholic fatty liver disease (NAFLD) is common worldwide and closely associated with metabolic dysfunction. NAFLD leads to a higher risk of development of severe liver diseases, such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). To date, no pharmacotherapy targeting NAFLD has received general approval. Adlay is a plant that has been used as traditional herbal medicine in Asia and is a promising candidate to solve this global issue. We have established a mouse model of NAFLD by feeding a high-fat diet (HFD) for 10 weeks. Here, ethanolic or water extracts of adlay seed (ASE and ASW, respectively), mixed with HFD, were fed to the mice for 10 weeks. The ASE and ASW treatment ameliorated hyperglycemia and improved the glucose tolerance and insulin resistance in the HFD mice. Hyperlipidemia in HFD mice was prevented by the ASE and ASW diet. In addition, the ASE and ASW supplementation attenuated hepatic steatosis and inflammation, improved liver function, and caused no harm to the kidneys. Moreover, the mechanism of the effect of ASE and ASW on inhibiting hepatic lipogenesis and inducing fatty acid β-oxidation was certified by the simulated human fatty liver cell model. Our study showed the regulatory potential of the extracts of adlay seeds for alleviating NAFLD, as well as related liver and metabolic diseases.

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Non-alcoholic fatty liver disease: modern methods of diagnostics and treatment strategies

Modern Gastroenterology ◽

10.30978/mg-2020-3-51 ◽

2020 ◽

Vol 0 (3) ◽

pp. 51-61

Author(s):

I. E. Kushnir

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Treatment Strategies ◽

Alcoholic Fatty Liver ◽

Modern Methods ◽

Alcoholic Fatty Liver Disease

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Targeting the GPR119/incretin axis: a promising new therapy for metabolic-associated fatty liver disease

Cellular & Molecular Biology Letters ◽

10.1186/s11658-021-00276-7 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Jianan Zhao ◽

Yu Zhao ◽

Yiyang Hu ◽

Jinghua Peng

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Drug Targets ◽

Metabolic Dysfunction ◽

Multiple Organs ◽

Glucose And Lipid Metabolism ◽

Potential Therapeutic Role ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

AbstractIn the past decade, G protein-coupled receptors have emerged as drug targets, and their physiological and pathological effects have been extensively studied. Among these receptors, GPR119 is expressed in multiple organs, including the liver. It can be activated by a variety of endogenous and exogenous ligands. After GPR119 is activated, the cell secretes a variety of incretins, including glucagon-like peptide-1 and glucagon-like peptide-2, which may attenuate the metabolic dysfunction associated with fatty liver disease, including improving glucose and lipid metabolism, inhibiting inflammation, reducing appetite, and regulating the intestinal microbial system. GPR119 has been a potential therapeutic target for diabetes mellitus type 2 for many years, but its role in metabolic dysfunction associated fatty liver disease deserves further attention. In this review, we discuss relevant research and current progress in the physiology and pharmacology of the GPR119/incretin axis and speculate on the potential therapeutic role of this axis in metabolic dysfunction associated with fatty liver disease, which provides guidance for transforming experimental research into clinical applications.

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Role of Insulin Resistance in MAFLD

International Journal of Molecular Sciences ◽

10.3390/ijms22084156 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4156

Author(s):

Yoshitaka Sakurai ◽

Naoto Kubota ◽

Toshimasa Yamauchi ◽

Takashi Kadowaki

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

De Novo Lipogenesis ◽

Hepatic Insulin Resistance ◽

Metabolic Dysfunction ◽

Alcoholic Fatty Liver ◽

Fat Accumulation

Many studies have reported that metabolic dysfunction is closely involved in the complex mechanism underlying the development of non-alcoholic fatty liver disease (NAFLD), which has prompted a movement to consider renaming NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD). Metabolic dysfunction in this context encompasses obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, with insulin resistance as the common underlying pathophysiology. Imbalance between energy intake and expenditure results in insulin resistance in various tissues and alteration of the gut microbiota, resulting in fat accumulation in the liver. The role of genetics has also been revealed in hepatic fat accumulation and fibrosis. In the process of fat accumulation in the liver, intracellular damage as well as hepatic insulin resistance further potentiates inflammation, fibrosis, and carcinogenesis. Increased lipogenic substrate supply from other tissues, hepatic zonation of Irs1, and other factors, including ER stress, play crucial roles in increased hepatic de novo lipogenesis in MAFLD with hepatic insulin resistance. Herein, we provide an overview of the factors contributing to and the role of systemic and local insulin resistance in the development and progression of MAFLD.

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Effects of Pyrroloquinoline Quinone on Lipid Metabolism and Anti-Oxidative Capacity in a High-Fat-Diet Metabolic Dysfunction-Associated Fatty Liver Disease Chick Model

International Journal of Molecular Sciences ◽

10.3390/ijms22031458 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1458

Author(s):

Kai Qiu ◽

Qin Zhao ◽

Jing Wang ◽

Guang-Hai Qi ◽

Shu-Geng Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Metabolism ◽

Liver Disease ◽

Fatty Liver ◽

Mitochondrial Biogenesis ◽

Fatty Liver Disease ◽

Laying Hens ◽

Oxidative Capacity ◽

Pyrroloquinoline Quinone ◽

Metabolic Dysfunction

Metabolic dysfunction-associated fatty liver disease (MAFLD) and its interaction with many metabolic pathways raises global public health concerns. This study aimed to determine the therapeutic effects of Pyrroloquinoline quinone (PQQ, provided by PQQ.Na2) on MAFLD in a chick model and primary chicken hepatocytes with a focus on lipid metabolism, anti-oxidative capacity, and mitochondrial biogenesis. The MAFLD chick model was established on laying hens by feeding them a high-energy low-protein (HELP) diet. Primary hepatocytes isolated from the liver of laying hens were induced for steatosis by free fatty acids (FFA) and for oxidative stress by hydrogen peroxide (H2O2). In the MAFLD chick model, the dietary supplementation of PQQ conspicuously ameliorated the negative effects of the HELP diet on liver biological functions, suppressed the progression of MAFLD mainly through enhanced lipid metabolism and protection of liver from oxidative injury. In the steatosis and oxidative stress cell models, PQQ functions in the improvement of the lipid metabolism and hepatocytes tolerance to fatty degradation and oxidative damage by enhancing mitochondrial biogenesis and then increasing the anti-oxidative activity and anti-apoptosis capacity. At both the cellular and individual levels, PQQ was demonstrated to exert protective effects of hepatocyte and liver from fat accumulation through the improvement of mitochondrial biogenesis and maintenance of redox homeostasis. The key findings of the present study provide an in-depth knowledge on the ameliorative effects of PQQ on the progression of fatty liver and its mechanism of action, thus providing a theoretical basis for the application of PQQ, as an effective nutrient, into the prevention of MAFLD.

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Coupling Machine Learning and Lipidomics as a Tool to Investigate Metabolic Dysfunction-Associated Fatty Liver Disease. A General Overview

Biomolecules ◽

10.3390/biom11030473 ◽

2021 ◽

Vol 11 (3) ◽

pp. 473

Author(s):

Helena Castañé ◽

Gerard Baiges-Gaya ◽

Anna Hernández-Aguilera ◽

Elisabet Rodríguez-Tomàs ◽

Salvador Fernández-Arroyo ◽

...

Keyword(s):

Machine Learning ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Predictive Biomarkers ◽

Metabolic Dysfunction ◽

Complex Situation ◽

Nonalcoholic Fatty Liver ◽

General Overview ◽

Diagnosis Accuracy

Hepatic biopsy is the gold standard for staging nonalcoholic fatty liver disease (NAFLD). Unfortunately, accessing the liver is invasive, requires a multidisciplinary team and is too expensive to be conducted on large segments of the population. NAFLD starts quietly and can progress until liver damage is irreversible. Given this complex situation, the search for noninvasive alternatives is clinically important. A hallmark of NAFLD progression is the dysregulation in lipid metabolism. In this context, recent advances in the area of machine learning have increased the interest in evaluating whether multi-omics data analysis performed on peripheral blood can enhance human interpretation. In the present review, we show how the use of machine learning can identify sets of lipids as predictive biomarkers of NAFLD progression. This approach could potentially help clinicians to improve the diagnosis accuracy and predict the future risk of the disease. While NAFLD has no effective treatment yet, the key to slowing the progression of the disease may lie in predictive robust biomarkers. Hence, to detect this disease as soon as possible, the use of computational science can help us to make a more accurate and reliable diagnosis. We aimed to provide a general overview for all readers interested in implementing these methods.

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