scholarly journals Intestinal Fructose and Glucose Metabolism in Health and Disease

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 94 ◽  
Author(s):  
Beatriz Merino ◽  
Cristina M. Fernández-Díaz ◽  
Irene Cózar-Castellano ◽  
German Perdomo
Keyword(s):  
Glucose Metabolism ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Sugar Metabolism ◽  
Sugar Consumption ◽  
Cellular Mechanisms ◽  
Obesity And Diabetes ◽  
Health And Disease ◽  
Dietary Sugars

The worldwide epidemics of obesity and diabetes have been linked to increased sugar consumption in humans. Here, we review fructose and glucose metabolism, as well as potential molecular mechanisms by which excessive sugar consumption is associated to metabolic diseases and insulin resistance in humans. To this end, we focus on understanding molecular and cellular mechanisms of fructose and glucose transport and sensing in the intestine, the intracellular signaling effects of dietary sugar metabolism, and its impact on glucose homeostasis in health and disease. Finally, the peripheral and central effects of dietary sugars on the gut–brain axis will be reviewed.

scholarly journals Circadian Mechanisms: Cardiac Ion Channel Remodeling and Arrhythmias

2021 ◽  
Vol 11 ◽  
Author(s):  
Joyce Bernardi ◽  
Kelly A. Aromolaran ◽  
Hua Zhu ◽  
Ademuyiwa S. Aromolaran
Keyword(s):  
Heart Failure ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Normal Sinus Rhythm ◽  
Critical Role ◽  
The United States ◽  
Therapeutic Interventions ◽  
Cellular Mechanisms ◽  
Normal Sinus ◽  
Obesity And Diabetes

Circadian rhythms are involved in many physiological and pathological processes in different tissues, including the heart. Circadian rhythms play a critical role in adverse cardiac function with implications for heart failure and sudden cardiac death, highlighting a significant contribution of circadian mechanisms to normal sinus rhythm in health and disease. Cardiac arrhythmias are a leading cause of morbidity and mortality in patients with heart failure and likely cause ∼250,000 deaths annually in the United States alone; however, the molecular mechanisms are poorly understood. This suggests the need to improve our current understanding of the underlying molecular mechanisms that increase vulnerability to arrhythmias. Obesity and its associated pathologies, including diabetes, have emerged as dangerous disease conditions that predispose to adverse cardiac electrical remodeling leading to fatal arrhythmias. The increasing epidemic of obesity and diabetes suggests vulnerability to arrhythmias will remain high in patients. An important objective would be to identify novel and unappreciated cellular mechanisms or signaling pathways that modulate obesity and/or diabetes. In this review we discuss circadian rhythms control of metabolic and environmental cues, cardiac ion channels, and mechanisms that predispose to supraventricular and ventricular arrhythmias including hormonal signaling and the autonomic nervous system, and how understanding their functional interplay may help to inform the development and optimization of effective clinical and therapeutic interventions with implications for chronotherapy.

scholarly journals Molecular Mechanisms of Cardiac Remodeling and Regeneration in Physical Exercise

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1128 ◽  
Author(s):  
Dominik Schüttler ◽  
Sebastian Clauss ◽  
Ludwig T. Weckbach ◽  
Stefan Brunner
Keyword(s):  
Cardiac Function ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Cardiac Tissue ◽  
Mammalian Target Of Rapamycin ◽  
Cellular Mechanisms ◽  
Innovative Strategies ◽  
Muscle Strengthening ◽  
Positive Effects ◽  
Exercise Induced

Regular physical activity with aerobic and muscle-strengthening training protects against the occurrence and progression of cardiovascular disease and can improve cardiac function in heart failure patients. In the past decade significant advances have been made in identifying mechanisms of cardiomyocyte re-programming and renewal including an enhanced exercise-induced proliferational capacity of cardiomyocytes and its progenitor cells. Various intracellular mechanisms mediating these positive effects on cardiac function have been found in animal models of exercise and will be highlighted in this review. 1) activation of extracellular and intracellular signaling pathways including phosphatidylinositol 3 phosphate kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), EGFR/JNK/SP-1, nitric oxide (NO)-signaling, and extracellular vesicles; 2) gene expression modulation via microRNAs (miR), in particular via miR-17-3p and miR-222; and 3) modulation of cardiac cellular metabolism and mitochondrial adaption. Understanding the cellular mechanisms, which generate an exercise-induced cardioprotective cellular phenotype with physiological hypertrophy and enhanced proliferational capacity may give rise to novel therapeutic targets. These may open up innovative strategies to preserve cardiac function after myocardial injury as well as in aged cardiac tissue.

scholarly journals The Intrinsic Virtues of EGCG, an Extremely Good Cell Guardian, on Prevention and Treatment of Diabesity Complications

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3061
Author(s):  
Maria Assunta Potenza ◽  
Dominga Iacobazzi ◽  
Luca Sgarra ◽  
Monica Montagnani
Keyword(s):  
Free Radicals ◽  
Chromatin Remodeling ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Cardiovascular Complications ◽  
Epigenetic Changes ◽  
Obesity And Diabetes ◽  
Membrane Target ◽  
Multiple Signaling ◽  
Pathologic Processes

The pandemic proportion of diabesity—a combination of obesity and diabetes—sets a worldwide health issue. Experimental and clinical studies have progressively reinforced the pioneering epidemiological observation of an inverse relationship between consumption of polyphenol-rich nutraceutical agents and mortality from cardiovascular and metabolic diseases. With chemical identification of epigallocatechin-3-gallate (EGCG) as the most abundant catechin of green tea, a number of cellular and molecular mechanisms underlying the activities of this unique catechin have been proposed. Favorable effects of EGCG have been initially attributed to its scavenging effects on free radicals, inhibition of ROS-generating mechanisms and upregulation of antioxidant enzymes. Biologic actions of EGCG are concentration-dependent and under certain conditions EGCG may exert pro-oxidant activities, including generation of free radicals. The discovery of 67-kDa laminin as potential EGCG membrane target has broaden the likelihood that EGCG may function not only because of its highly reactive nature, but also via receptor-mediated activation of multiple signaling pathways involved in cell proliferation, angiogenesis and apoptosis. Finally, by acting as epigenetic modulator of DNA methylation and chromatin remodeling, EGCG may alter gene expression and modify miRNA activities. Despite unceasing research providing detailed insights, ECGC composite activities are still not completely understood. This review summarizes the most recent evidence on molecular mechanisms by which EGCG may activate signal transduction pathways, regulate transcription factors or promote epigenetic changes that may contribute to prevent pathologic processes involved in diabesity and its cardiovascular complications.

scholarly journals Potential Functions of the BMP Family in Bone, Obesity, and Glucose Metabolism

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yao Chen ◽  
Bingwei Ma ◽  
Xingchun Wang ◽  
Xiaojuan Zha ◽  
Chunjun Sheng ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Bone Metabolism ◽  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Metabolic Diseases ◽  
Cellular Functions ◽  
Mineral Density ◽  
Pathophysiological Process ◽  
Obesity And Diabetes

Characteristic bone metabolism was observed in obesity and diabetes with controversial conclusions. Type 2 diabetes (T2DM) and obesity may manifest increased bone mineral density. Also, obesity is more easily to occur in T2DM. Therefore, we infer that some factors may be linked to bone and obesity as well as glucose metabolism, which regulate all of them. Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor- (TGF-) beta superfamily, regulate a diverse array of cellular functions during development and in the adult. More and more studies revealed that there exists a relationship between bone metabolism and obesity as well as glucose metabolism. BMP2, BMP4, BMP6, BMP7, and BMP9 have been shown to affect the pathophysiological process of obesity and glucose metabolism beyond bone metabolism. They may exert functions in adipogenesis and differentiation as well as insulin resistance. In the review, we summarize the literature on these BMPs and their association with metabolic diseases including obesity and diabetes.

scholarly journals Integrative Metabolomics to Identify Molecular Signatures of Responses to Vaccines and Infections

2020 ◽  
Author(s):  
Joann Diray-Arce ◽  
Maria-Giulia Conti ◽  
Boryana Petrova ◽  
Naama Kanarek ◽  
Asimenia Angelidou ◽  
...  
Keyword(s):  
Host Response ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
High Dimensional ◽  
Molecular Signatures ◽  
Biochemical Pathway ◽  
Innate And Adaptive Immunity ◽  
Health And Disease ◽  
Fresh Insight ◽  
Insight Into

Approaches to identification of metabolites have progressed from early biochemical pathway evaluation to modern high dimensional metabolomics which is a powerful tool to identify and characterize biomarkers of health and disease. While traditionally considered relevant in the context of classic metabolic diseases, immunometabolism has emerged as an important area of study as leukocytes generate key metabolites important to innate and adaptive immunity. Herein we discuss the metabolomic signatures and pathways perturbed during infection as well as vaccination. For example, changes in lipid and amino acid pathways (e.g., tryptophan, serine, and threonine) have been noted during infection while carbohydrate and bile acid pathways have shift upon vaccination. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying host response to infection and vaccination, and its integration with other systems biology platforms will add further impact to our studies of health and disease.

scholarly journals DNA methylation: the pivotal interaction between early-life nutrition and glucose metabolism in later life

2014 ◽  
Vol 112 (11) ◽  
pp. 1850-1857 ◽  
Author(s):  
Jia Zheng ◽  
Xinhua Xiao ◽  
Qian Zhang ◽  
Miao Yu
Keyword(s):  
Gene Expression ◽  
Glucose Metabolism ◽  
Early Life ◽  
Metabolic Diseases ◽  
Disease Risk ◽  
Critical Role ◽  
Critical Time ◽  
Later Life ◽  
Specific Gene ◽  
Obesity And Diabetes

Traditionally, it has been widely acknowledged that genes together with adult lifestyle factors determine the risk of developing some metabolic diseases such as insulin resistance, obesity and diabetes mellitus in later life. However, there is now substantial evidence that prenatal and early-postnatal nutrition play a critical role in determining susceptibility to these diseases in later life. Maternal nutrition has historically been a key determinant for offspring health, and gestation is the critical time window that can affect the growth and development of offspring. The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that exposures during early life play a critical role in determining the risk of developing metabolic diseases in adulthood. Currently, there are substantial epidemiological studies and experimental animal models that have demonstrated that nutritional disturbances during the critical periods of early-life development can significantly have an impact on the predisposition to developing some metabolic diseases in later life. The hypothesis that epigenetic mechanisms may link imbalanced early-life nutrition with altered disease risk has been widely accepted in recent years. Epigenetics can be defined as the study of heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic processes play a significant role in regulating tissue-specific gene expression, and hence alterations in these processes may induce long-term changes in gene function and metabolism that persist throughout the life course. The present review focuses on how nutrition in early life can alter the epigenome, produce different phenotypes and alter disease susceptibilities, especially for impaired glucose metabolism.

scholarly journals Hydrogen Therapy in Cardiovascular and Metabolic Diseases: from Bench to Bedside

2018 ◽  
Vol 47 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Yaxing Zhang ◽  
Sihua Tan ◽  
Jingting Xu ◽  
Tinghuai Wang
Keyword(s):  
Molecular Mechanisms ◽  
Ventricular Remodeling ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Chemical Properties ◽  
Obesity And Diabetes ◽  
Gas Molecules ◽  
Heart Injury ◽  
Physical And Chemical ◽  
And Chemical Properties

Hydrogen (H2) is colorless, odorless, and the lightest of gas molecules. Studies in the past ten years have indicated that H2 is extremely important in regulating the homeostasis of the cardiovascular system and metabolic activity. Delivery of H2 by various strategies improves cardiometabolic diseases, including atherosclerosis, vascular injury, ischemic or hypertrophic ventricular remodeling, intermittent hypoxia- or heart transplantation-induced heart injury, obesity and diabetes in animal models or in clinical trials. The purpose of this review is to summarize the physical and chemical properties of H2, and then, the functions of H2 with an emphasis on the therapeutic potential and molecular mechanisms involved in the diseases above. We hope this review will provide the future outlook of H2-based therapies for cardiometabolic disease.

Transgenic GLUT-4 overexpression in fat enhances glucose metabolism: preferential effect on fatty acid synthesis

1995 ◽  
Vol 268 (5) ◽  
pp. E956-E964 ◽  
Author(s):  
E. Tozzo ◽  
P. R. Shepherd ◽  
L. Gnudi ◽  
B. B. Kahn
Keyword(s):  
Fatty Acid ◽  
Glucose Metabolism ◽  
Transgenic Mice ◽  
Fatty Acid Synthesis ◽  
Glucose Concentration ◽  
Molecular Mechanisms ◽  
Acid Synthesis ◽  
Glut 4 ◽  
Obesity And Diabetes ◽  
The Impact

GLUT-4 expression varies widely among normal humans and those with obesity and diabetes. Using the alpha P2 promoter/enhancer ligated to the human GLUT-4 gene, we created transgenic mice to study the impact of alterations in GLUT-4 expression selectively in adipocytes on glucose homeostasis and body composition. Here we investigated molecular mechanisms for enhanced glucose tolerance and obesity in these mice. [U-14C]glucose incorporation into triglycerides, glyceride-glycerol, glyceride-fatty acids, CO2, and lactate was measured in adipocytes incubated at 3, 0.5, and 3 microM glucose with or without maximally stimulating insulin. In nontransgenic and transgenic mice, the major pathway for glucose metabolism shifts from lipogenesis at tracer glucose concentration to glycolysis at physiological glucose concentration. In transgenic adipocytes incubated at 3 microM glucose, metabolism via all major pathways is enhanced by 8.6- to 38-fold in the absence of insulin and 3- to 13-fold in the presence of insulin. At physiological glucose concentration, constitutive metabolism to triglycerides, CO2, and lactate is two- to threefold greater in transgenic than in nontransgenic adipocytes. De novo fatty acid synthesis is preferentially increased: 31-fold for basal and 21-fold for insulin-stimulated compared with nontransgenic adipocytes. Thus overexpression of GLUT-4 in adipocytes of transgenic mice results in increased glucose metabolism in all major pathways, with differential regulation of the pathways involved in lipogenesis.

scholarly journals Integrative Metabolomics to Identify Molecular Signatures of Responses to Vaccines and Infections

Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 492
Author(s):  
Joann Diray-Arce ◽  
Maria Giulia Conti ◽  
Boryana Petrova ◽  
Naama Kanarek ◽  
Asimenia Angelidou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Nucleotide Metabolism ◽  
Human Immune System ◽  
Innate And Adaptive Immunity ◽  
Health And Disease ◽  
Human Immune ◽  
Fresh Insight ◽  
Insight Into

Approaches to the identification of metabolites have progressed from early biochemical pathway evaluation to modern high-dimensional metabolomics, a powerful tool to identify and characterize biomarkers of health and disease. In addition to its relevance to classic metabolic diseases, metabolomics has been key to the emergence of immunometabolism, an important area of study, as leukocytes generate and are impacted by key metabolites important to innate and adaptive immunity. Herein, we discuss the metabolomic signatures and pathways perturbed by the activation of the human immune system during infection and vaccination. For example, infection induces changes in lipid (e.g., free fatty acids, sphingolipids, and lysophosphatidylcholines) and amino acid pathways (e.g., tryptophan, serine, and threonine), while vaccination can trigger changes in carbohydrate and bile acid pathways. Amino acid, carbohydrate, lipid, and nucleotide metabolism is relevant to immunity and is perturbed by both infections and vaccinations. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying the host immune response. Its integration with other systems biology platforms will enhance studies of human health and disease.

Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes

2005 ◽  
Vol 99 (5) ◽  
pp. 2008-2019 ◽  
Author(s):  
Karine Spiegel ◽  
Kristen Knutson ◽  
Rachel Leproult ◽  
Esra Tasali ◽  
Eve Van Cauter
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Risk Factor ◽  
Weight Gain ◽  
Glucose Metabolism ◽  
Molecular Mechanisms ◽  
Sleep Loss ◽  
Obesity And Diabetes ◽  
Chronic Sleep

Chronic sleep loss as a consequence of voluntary bedtime restriction is an endemic condition in modern society. Although sleep exerts marked modulatory effects on glucose metabolism, and molecular mechanisms for the interaction between sleeping and feeding have been documented, the potential impact of recurrent sleep curtailment on the risk for diabetes and obesity has only recently been investigated. In laboratory studies of healthy young adults submitted to recurrent partial sleep restriction, marked alterations in glucose metabolism including decreased glucose tolerance and insulin sensitivity have been demonstrated. The neuroendocrine regulation of appetite was also affected as the levels of the anorexigenic hormone leptin were decreased, whereas the levels of the orexigenic factor ghrelin were increased. Importantly, these neuroendocrine abnormalities were correlated with increased hunger and appetite, which may lead to overeating and weight gain. Consistent with these laboratory findings, a growing body of epidemiological evidence supports an association between short sleep duration and the risk for obesity and diabetes. Chronic sleep loss may also be the consequence of pathological conditions such as sleep-disordered breathing. In this increasingly prevalent syndrome, a feedforward cascade of negative events generated by sleep loss, sleep fragmentation, and hypoxia are likely to exacerbate the severity of metabolic disturbances. In conclusion, chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.

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