scholarly journals The asymmetric Pitx2 regulates intestinal muscular-lacteal development and protects against fatty liver disease

2021 ◽  
Author(s):  
Natasza A Kurpios ◽  
Shing Hu ◽  
Aparna Mahadevan ◽  
Isaac F Elysee ◽  
Joseph Choi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Dietary Lipids ◽  
Lipid Transport ◽  
Disease Etiology ◽  
Important Relationship ◽  
Organ Specific ◽  
Lymphatic Development

Intestinal lacteals are the essential lymphatic channels for absorption and transport of dietary lipids and drive pathogenesis of debilitating metabolic diseases. Yet, organ-specific mechanisms linking lymphatic dysfunction to disease etiology remain largely unknown. In this study, we uncover a novel intestinal lymphatic program that is linked to the left-right (LR) asymmetric transcription factor Pitx2. We show that deletion of the asymmetric Pitx2 enhancer, ASE, alters normal lacteal development through the lacteal-associated contractile smooth muscle lineage. ASE deletion leads to abnormal muscle morphogenesis induced by oxidative stress, resulting in impaired lacteal extension and defective lymphatic-dependent lipid transport. Surprisingly, activation of lymphatic-independent trafficking directs dietary lipids from the gut directly to the liver, causing diet-induced fatty liver disease. In summary, our studies reveal the molecular mechanism linking gut lymphatic development to the earliest symmetry-breaking Pitx2 and highlight the important relationship between intestinal lymphangiogenesis and gut-liver axis.

Impaired Antioxidant Status in Non-Organ Specific Autoantibody Positive Patients with Non-Alcoholic Fatty Liver Disease

2008 ◽  
Vol 2 (4) ◽  
pp. 563-570 ◽  
Author(s):  
Krisztina Hagymási ◽  
Gabriella Lengyel ◽  
Eszter Nagy ◽  
Zsolt Pallai ◽  
Ibolya Kocsis ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Antioxidant Status ◽  
Alcoholic Fatty Liver ◽  
Organ Specific ◽  
Specific Autoantibody ◽  
Alcoholic Fatty Liver Disease

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

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.

scholarly journals Targeted Nutrient Modifications in Purified Diets Differentially Affect Nonalcoholic Fatty Liver Disease and Metabolic Disease Development in Rodent Models

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Sridhar Radhakrishnan ◽  
Jia-Yu Ke ◽  
Michael A Pellizzon
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Complex Spectrum ◽  
Disease Development ◽  
Rodent Models ◽  
Nonalcoholic Fatty Liver ◽  
Time Frames

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is a complex spectrum of disorders ranging from simple benign steatosis to more aggressive forms of nonalcoholic steatohepatitis (NASH) and fibrosis. Although not every patient with NAFLD/NASH develops liver complications, if left untreated it may eventually lead to cirrhosis and hepatocellular carcinoma. Purified diets formulated with specific nutritional components can drive the entire spectrum of NAFLD in rodent models. Although they may not perfectly replicate the clinical and histological features of human NAFLD, they provide a model to gain further understanding of disease progression in humans. Owing to the growing demand of diets for NAFLD research, and for our further understanding of how manipulation of dietary components can alter disease development, we outlined several commonly used dietary approaches for rodent models, including mice, rats, and hamsters, time frames required for disease development and whether other metabolic diseases commonly associated with NAFLD in humans occur.

scholarly journals Beneficial Effect of Pachyrhizus erosus Fiber as a Supplemental Diet to Counteract High Sugar-Induced Fatty Liver Disease in Mice

2019 ◽  
Vol 26 (4) ◽  
pp. 353-360
Author(s):  
Putra Santoso ◽  
Rita Maliza ◽  
Qonitah Fadhilah ◽  
Siti Jamalul Insani
Keyword(s):  
Liver Disease ◽  
Beneficial Effect ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Alcoholic Fatty Liver ◽  
High Sugar ◽  
End Of Treatment ◽  
Pachyrhizus Erosus ◽  
Excessive Intake

Abstract Background and aims: Edible fiber isolated from the tuber of yam bean (Pachyrhizus erosus, Leguminosae) has been suggested to prevent the development of metabolic diseases caused by excessively consuming sugary foods. However, it is unclarified whether P. erosus fiber (PEF) is also capable of preventing liver diseases. This study aimed to determine the effectivity of PEF in counteracting the development of non-alcoholic fatty liver disease (NAFLD) caused by excessive intake of high-sugar diet (HSD). Material and method: 25% of PEF in HSD (w/w) was fed in BALB/c mice for eight weeks followed by subsequent morphological and histological examinations of the liver at the end of treatment in comparing with HSD alone. Results: We found that supplementation of 25% PEF sustained the normal morphological feature of the liver in HSD-fed mice. Moreover, PEF also prevented the development of microvesicles in the liver tissue, nuclear shrinkage, and hepatolysis as indicators of liver disease. Macrophages infiltration as a marker of liver inflammation was also less observed in PEF-treated mice. Conclusions: PEF could effectively elicit a beneficial effect against NAFLD caused by HSD. Hence, PEF is suggested to be used as a potent supplemental diet to preclude the metabolic diseases caused by HSD.

scholarly journals Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Therapy

2017 ◽  
Author(s):  
Junli Ma ◽  
Qihang Zhou ◽  
Houkai Li
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Targeted Therapies ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Herbal Medicines ◽  
Active Components ◽  
Nonalcoholic Fatty Liver

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first reviewed the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies on NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

scholarly journals Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Therapy

2017 ◽  
Author(s):  
Junli Ma ◽  
Qihang Zhou ◽  
Houkai Li
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Targeted Therapies ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Herbal Medicines ◽  
Active Components ◽  
Nonalcoholic Fatty Liver

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first described the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies in NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

scholarly journals Non-alcoholic fatty liver disease: current aspects of diagnosis in real clinical practice

2021 ◽  
Vol 2 (4) ◽  
pp. 40-50
Author(s):  
Dmitry I. Trukhan ◽  
Keyword(s):  
Clinical Practice ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Diagnostic Algorithm ◽  
Malignant Neoplasms ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease ◽  
Real Clinical Practice

In the diagnosis and subsequent supervision of patients with non-alcoholic fatty liver disease (NAFLD) and obesity in real clinical practice, the role and importance of the doctor of first contact (therapist and general practitioner) increases. Non-alcoholic fatty liver disease is currently considered as the hepatic component of metabolic syndrome. A diagnostic algorithm for NAFLD at the stage of primary health care is presented. The most difficult question at 2–4 levels of the diagnostic algorithm is the differential diagnosis between NAFLD and alcoholic liver disease. During a pandemic of a novel coronavirus infection (COVID-19), patients with NAFLD or NASH, as a rule, have concomitant metabolic diseases such as diabetes mellitus, arterial hypertension and obesity, and also have to take a large number of potentially hepatotoxic drugs, it is advisable to classify them as elevated risk of infection with SARS-CoV-2, and the severe course of this infection. This allows us to consider NAFLD as dangerous in terms of the severe course of COVID-19, as viral hepatitis, autoimmune hepatitis and liver fibrosis / cirrhosis. It is known that NAFLD is an independent predictor of not only high cardiovascular risks, but also hepatocellular carcinoma and malignant neoplasms of various localization, as well as a number of other comorbid conditions. The review concludes with a clinical observation illustrating the difficulty of early diagnosis of intrahepatic cholangiocarcinoma in a patient with NAFLD and other metabolic risk factors.

scholarly journals Hepatokines and Non-Alcoholic Fatty Liver Disease: Linking Liver Pathophysiology to Metabolism

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1903
Author(s):  
Tae Hyun Kim ◽  
Dong-Gyun Hong ◽  
Yoon Mee Yang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Therapeutic Targets ◽  
Signaling Crosstalk ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The liver plays a key role in maintaining energy homeostasis by sensing and responding to changes in nutrient status under various metabolic conditions. Recently highlighted as a major endocrine organ, the contribution of the liver to systemic glucose and lipid metabolism is primarily attributed to signaling crosstalk between multiple organs via hepatic hormones, cytokines, and hepatokines. Hepatokines are hormone-like proteins secreted by hepatocytes, and a number of these have been associated with extra-hepatic metabolic regulation. Mounting evidence has revealed that the secretory profiles of hepatokines are significantly altered in non-alcoholic fatty liver disease (NAFLD), the most common hepatic manifestation, which frequently precedes other metabolic disorders, including insulin resistance and type 2 diabetes. Therefore, deciphering the mechanism of hepatokine-mediated inter-organ communication is essential for understanding the complex metabolic network between tissues, as well as for the identification of novel diagnostic and/or therapeutic targets in metabolic disease. In this review, we describe the hepatokine-driven inter-organ crosstalk in the context of liver pathophysiology, with a particular focus on NAFLD progression. Moreover, we summarize key hepatokines and their molecular mechanisms of metabolic control in non-hepatic tissues, discussing their potential as novel biomarkers and therapeutic targets in the treatment of metabolic diseases.

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