scholarly journals Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhensheng Cai ◽  
Xia Deng ◽  
Jue Jia ◽  
Dong Wang ◽  
Guoyue Yuan
Keyword(s):  
Metabolic Diseases ◽  
Ectodermal Dysplasia ◽  
Splice Variants ◽  
Prenatal Development ◽  
Death Domain ◽  
Receptor System ◽  
Alcoholic Fatty Liver ◽  
And Migration ◽  
Tumor Pathogenesis

Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.

scholarly journals The Protective Role of Butyrate against Obesity and Obesity-Related Diseases

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 682
Author(s):  
Serena Coppola ◽  
Carmen Avagliano ◽  
Antonio Calignano ◽  
Roberto Berni Canani
Keyword(s):  
Metabolic Diseases ◽  
Environmental Changes ◽  
Short Chain Fatty Acids ◽  
Protective Role ◽  
Health Concern ◽  
Predisposing Factor ◽  
Alcoholic Fatty Liver ◽  
Beneficial Effects ◽  
The Individual

Worldwide obesity is a public health concern that has reached pandemic levels. Obesity is the major predisposing factor to comorbidities, including type 2 diabetes, cardiovascular diseases, dyslipidemia, and non-alcoholic fatty liver disease. The common forms of obesity are multifactorial and derive from a complex interplay of environmental changes and the individual genetic predisposition. Increasing evidence suggest a pivotal role played by alterations of gut microbiota (GM) that could represent the causative link between environmental factors and onset of obesity. The beneficial effects of GM are mainly mediated by the secretion of various metabolites. Short-chain fatty acids (SCFAs) acetate, propionate and butyrate are small organic metabolites produced by fermentation of dietary fibers and resistant starch with vast beneficial effects in energy metabolism, intestinal homeostasis and immune responses regulation. An aberrant production of SCFAs has emerged in obesity and metabolic diseases. Among SCFAs, butyrate emerged because it might have a potential in alleviating obesity and related comorbidities. Here we reviewed the preclinical and clinical data that contribute to explain the role of butyrate in this context, highlighting its crucial contribute in the diet-GM-host health axis.

scholarly journals Glucose-6 Phosphate, a Central Hub for Liver Carbohydrate Metabolism

Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 282 ◽  
Author(s):  
Fabienne Rajas ◽  
Amandine Gautier-Stein ◽  
Gilles Mithieux
Keyword(s):  
Glucose Metabolism ◽  
Metabolic Diseases ◽  
De Novo ◽  
Glycogen Synthesis ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Type I ◽  
Alcoholic Fatty Liver ◽  
Hexosamine Pathway

Cells efficiently adjust their metabolism according to the abundance of nutrients and energy. The ability to switch cellular metabolism between anabolic and catabolic processes is critical for cell growth. Glucose-6 phosphate is the first intermediate of glucose metabolism and plays a central role in the energy metabolism of the liver. It acts as a hub to metabolically connect glycolysis, the pentose phosphate pathway, glycogen synthesis, de novo lipogenesis, and the hexosamine pathway. In this review, we describe the metabolic fate of glucose-6 phosphate in a healthy liver and the metabolic reprogramming occurring in two pathologies characterized by a deregulation of glucose homeostasis, namely type 2 diabetes, which is characterized by fasting hyperglycemia; and glycogen storage disease type I, where patients develop severe hypoglycemia during short fasting periods. In these two conditions, dysfunction of glucose metabolism results in non-alcoholic fatty liver disease, which may possibly lead to the development of hepatic tumors. Moreover, we also emphasize the role of the transcription factor carbohydrate response element-binding protein (ChREBP), known to link glucose and lipid metabolisms. In this regard, comparing these two metabolic diseases is a fruitful approach to better understand the key role of glucose-6 phosphate in liver metabolism in health and disease.

scholarly journals Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7716
Author(s):  
Caterina Formichi ◽  
Laura Nigi ◽  
Giuseppina Emanuela Grieco ◽  
Carla Maccora ◽  
Daniela Fignani ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Diseases ◽  
Gene Expression Regulation ◽  
Biological Fluids ◽  
Current Evidence ◽  
Alcoholic Fatty Liver ◽  
Non Coding Rnas ◽  
Alcoholic Fatty Liver Disease

The rising prevalence of metabolic diseases related to insulin resistance (IR) have stressed the urgent need of accurate and applicable tools for early diagnosis and treatment. In the last decade, non-coding RNAs (ncRNAs) have gained growing interest because of their potential role in IR modulation. NcRNAs are variable-length transcripts which are not translated into proteins but are involved in gene expression regulation. Thanks to their stability and easy detection in biological fluids, ncRNAs have been investigated as promising diagnostic and therapeutic markers in metabolic diseases, such as type 2 diabetes mellitus (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). Here we review the emerging role of ncRNAs in the development of IR and related diseases such as obesity, T2D and NAFLD, and summarize current evidence concerning their potential clinical application.

scholarly journals Fructose and Uric Acid: Major Mediators of Cardiovascular Disease Risk Starting at Pediatric Age

2020 ◽  
Vol 21 (12) ◽  
pp. 4479 ◽  
Author(s):  
Elisa Russo ◽  
Giovanna Leoncini ◽  
Pasquale Esposito ◽  
Giacomo Garibotto ◽  
Roberto Pontremoli ◽  
...  
Keyword(s):  
Uric Acid ◽  
Metabolic Diseases ◽  
Disease Risk ◽  
Chronic Renal Disease ◽  
Cardiovascular Disease Risk ◽  
Pediatric Age ◽  
Biological Mechanisms ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Recently, there has been a growing interest in epidemiological and clinical studies supporting a pathogenetic role of fructose in cardio-metabolic diseases, especially in children and adolescents. In the present review, we summarize experimental data on the potential biological mechanisms linking fructose and uric acid in the development of insulin resistance, metabolic syndrome, obesity, diabetes, hypertension, non-alcoholic fatty liver disease and chronic renal disease, thereby contributing to an increase in cardiovascular risk at pediatric age.

scholarly journals Immunomodulatory Role of Urolithin A on Metabolic Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 192
Author(s):  
Ashley Mulcahy Toney ◽  
Darius Fox ◽  
Virginia Chaidez ◽  
Amanda E. Ramer-Tait ◽  
Soonkyu Chung
Keyword(s):  
Ellagic Acid ◽  
Dietary Intervention ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Alcoholic Fatty Liver ◽  
Urolithin A ◽  
Anti Inflammatory ◽  
The Brain

Urolithin A (UroA) is a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries, and walnuts. UroA is of growing interest due to its therapeutic potential for various metabolic diseases based on immunomodulatory properties. Recent advances in UroA research suggest that UroA administration attenuates inflammation in various tissues, including the brain, adipose, heart, and liver tissues, leading to the potential delay or prevention of the onset of Alzheimer’s disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In this review, we focus on recent updates of the anti-inflammatory function of UroA and summarize the potential mechanisms by which UroA may help attenuate the onset of diseases in a tissue-specific manner. Therefore, this review aims to shed new insights into UroA as a potent anti-inflammatory molecule to prevent immunometabolic diseases, either by dietary intervention with ellagic acid-rich food or by UroA administration as a new pharmaceutical drug.

scholarly journals New Insights Into the Role of Autophagy in Liver Surgery in the Setting of Metabolic Syndrome and Related Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Ana Isabel Álvarez-Mercado ◽  
Carlos Rojano-Alfonso ◽  
Marc Micó-Carnero ◽  
Albert Caballeria-Casals ◽  
Carmen Peralta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Resection ◽  
Liver Function ◽  
Liver Surgery ◽  
Metabolic Diseases ◽  
Liver Graft ◽  
Postoperative Results ◽  
Alcoholic Fatty Liver

Visceral obesity is an important component of metabolic syndrome, a cluster of diseases that also includes diabetes and insulin resistance. A combination of these metabolic disorders damages liver function, which manifests as non-alcoholic fatty liver disease (NAFLD). NAFLD is a common cause of abnormal liver function, and numerous studies have established the enormously deleterious role of hepatic steatosis in ischemia-reperfusion (I/R) injury that inevitably occurs in both liver resection and transplantation. Thus, steatotic livers exhibit a higher frequency of post-surgical complications after hepatectomy, and using liver grafts from donors with NAFLD is associated with an increased risk of post-surgical morbidity and mortality in the recipient. Diabetes, another MetS-related metabolic disorder, also worsens hepatic I/R injury, and similar to NAFLD, diabetes is associated with a poor prognosis after liver surgery. Due to the large increase in the prevalence of MetS, NAFLD, and diabetes, their association is frequent in the population and therefore, in patients requiring liver resection and in potential liver graft donors. This scenario requires advancement in therapies to improve postoperative results in patients suffering from metabolic diseases and undergoing liver surgery; and in this sense, the bases for designing therapeutic strategies are in-depth knowledge about the molecular signaling pathways underlying the effects of MetS-related diseases and I/R injury on liver tissue. A common denominator in all these diseases is autophagy. In fact, in the context of obesity, autophagy is profoundly diminished in hepatocytes and alters mitochondrial functions in the liver. In insulin resistance conditions, there is a suppression of autophagy in the liver, which is associated with the accumulation of lipids, being this is a risk factor for NAFLD. Also, oxidative stress occurring in hepatic I/R injury promotes autophagy. The present review aims to shed some light on the role of autophagy in livers undergoing surgery and also suffering from metabolic diseases, which may lead to the discovery of effective therapeutic targets that could be translated from laboratory to clinical practice, to improve postoperative results of liver surgeries when performed in the presence of one or more metabolic diseases.

scholarly journals Arachidonic Acid Metabolites in Cardiovascular and Metabolic Diseases

2018 ◽  
Vol 19 (11) ◽  
pp. 3285 ◽  
Author(s):  
Thomas Sonnweber ◽  
Alex Pizzini ◽  
Manfred Nairz ◽  
Günter Weiss ◽  
Ivan Tancevski
Keyword(s):  
Cardiovascular Disease ◽  
Arachidonic Acid ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Nutrient Metabolism ◽  
Alcoholic Fatty Liver ◽  
Acid Metabolites ◽  
Immune Pathways ◽  
Alcoholic Fatty Liver Disease

Lipid and immune pathways are crucial in the pathophysiology of metabolic and cardiovascular disease. Arachidonic acid (AA) and its derivatives link nutrient metabolism to immunity and inflammation, thus holding a key role in the emergence and progression of frequent diseases such as obesity, diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. We herein present a synopsis of AA metabolism in human health, tissue homeostasis, and immunity, and explore the role of the AA metabolome in diverse pathophysiological conditions and diseases.

scholarly journals Disease, Drugs and Dysbiosis: Understanding Microbial Signatures in Metabolic Disease and Medical Interventions

2020 ◽  
Vol 8 (9) ◽  
pp. 1381
Author(s):  
Ceri Proffitt ◽  
Gholamreza Bidkhori ◽  
David Moyes ◽  
Saeed Shoaie
Keyword(s):  
Metabolic Disease ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Alcoholic Fatty Liver ◽  
Medical Interventions ◽  
Microbial Dysbiosis ◽  
Health And Disease ◽  
Alcoholic Fatty Liver Disease

Since the discovery of the potential role for the gut microbiota in health and disease, many studies have gone on to report its impact in various pathologies. These studies have fuelled interest in the microbiome as a potential new target for treating disease Here, we reviewed the key metabolic diseases, obesity, type 2 diabetes and atherosclerosis and the role of the microbiome in their pathogenesis. In particular, we will discuss disease associated microbial dysbiosis; the shift in the microbiome caused by medical interventions and the altered metabolite levels between diseases and interventions. The microbial dysbiosis seen was compared between diseases including Crohn’s disease and ulcerative colitis, non-alcoholic fatty liver disease, liver cirrhosis and neurodegenerative diseases, Alzheimer’s and Parkinson’s. This review highlights the commonalities and differences in dysbiosis of the gut between diseases, along with metabolite levels in metabolic disease vs. the levels reported after an intervention. We identify the need for further analysis using systems biology approaches and discuss the potential need for treatments to consider their impact on the microbiome.

scholarly journals Potential of Nutraceutical Supplementation in the Modulation of White and Brown Fat Tissues in Obesity-Associated Disorders: Role of Inflammatory Signalling

2021 ◽  
Vol 22 (7) ◽  
pp. 3351
Author(s):  
Federica Scarano ◽  
Micaela Gliozzi ◽  
Maria Caterina Zito ◽  
Lorenza Guarnieri ◽  
Cristina Carresi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Mediators ◽  
Metabolic Diseases ◽  
Potential Effect ◽  
Alcoholic Fatty Liver ◽  
Adipose Tissue Dysfunction ◽  
Brown Adipose ◽  
Inflammatory State ◽  
Inflammatory Signalling

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.

scholarly journals Role of hepatokines in non-alcoholic fatty liver disease

2019 ◽  
Vol 7 (4) ◽  
pp. 143-148 ◽  
Author(s):  
Yini Ke ◽  
Chengfu Xu ◽  
Jin Lin ◽  
Youming Li
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Alcoholic Fatty Liver ◽  
Diabetes And Obesity ◽  
Alcoholic Fatty Liver Disease ◽  
Muscular Tissues

Abstract Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic diseases like type 2 diabetes and obesity. In recent decades, accumulating evidence has revealed that the hepatokines, proteins mainly secreted by the liver, play important roles in the development of NAFLD by acting directly on the lipid and glucose metabolism. As a member of organokines, the hepatokines establish the communication between the liver and the adipose, muscular tissues. In this review, we summarize the current understanding of the hepatokines and how they modulate the pathogenesis of metabolic disorders especially NAFLD.

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