Association and Interaction Between Serum Interleukin-6 Levels and Metabolic Dysfunction-Associated Fatty Liver Disease in Patients With Severe Coronavirus Disease 2019

Background and AimCirculating levels of interleukin (IL)-6, a well-known inflammatory cytokine, are often elevated in coronavirus disease-2019 (COVID-19). Elevated IL-6 levels are also observed in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Our study aimed to describe the association between circulating IL-6 levels and MAFLD at hospital admission with risk of severe COVID-19.MethodsA total of 167 patients with laboratory-confirmed COVID-19 from three Chinese hospitals were enrolled. Circulating levels of IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured at admission. All patients were screened for fatty liver by computed tomography. Forty-six patients were diagnosed as MAFLD.ResultsPatients with MAFLD (n = 46) had higher serum IL-6 levels (median 7.1 [interquartile range, 4.3–20.0] vs. 4.8 [2.6–11.6] pg/mL, p = 0.030) compared to their counterparts without MAFLD (n = 121). After adjustment for age and sex, patients with MAFLD had a ~2.6-fold higher risk of having severe COVID-19 than those without MAFLD. After adjustment for age, sex and metabolic co-morbidities, increased serum IL-6 levels remained associated with higher risk of severe COVID-19, especially among infected patients with MAFLD (adjusted-odds ratio 1.14, 95% CI 1.05–1.23; p = 0.002). There was a significant interaction effect between serum IL-6 levels and MAFLD for risk of severe COVID-19 (p for interaction = 0.008).ConclusionsPatients with MAFLD and elevated serum IL-6 levels at admission are at higher risk for severe illness from COVID-19.

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Risk of severe illness from COVID-19 in patients with metabolic dysfunction-associated fatty liver disease and increased fibrosis scores

Gut ◽

10.1136/gutjnl-2020-321611 ◽

2020 ◽

Vol 69 (8) ◽

pp. 1545-1547 ◽

Cited By ~ 21

Author(s):

Giovanni Targher ◽

Alessandro Mantovani ◽

Christopher D Byrne ◽

Xiao-Bo Wang ◽

Hua-Dong Yan ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Severe Illness ◽

Metabolic Dysfunction

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

International Journal of Molecular Sciences ◽

10.3390/ijms22084241 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4241

Author(s):

Revathy Carnagarin ◽

Kearney Tan ◽

Leon Adams ◽

Vance B. Matthews ◽

Marcio G. Kiuchi ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Metabolic Diseases ◽

Treatment Strategies ◽

Adverse Outcomes ◽

Metabolic Dysfunction ◽

Sympathetic Activation ◽

Beneficial Effects ◽

Adverse Health Outcomes

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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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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