Bile Acid Signaling in Metabolic Disease and Drug Therapy

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Li, Tiangang

2014-01-01

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid–activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein–coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver. PMID:25073467

Metaflammation, NLRP3 Inflammasome Obesity and Metabolic Disease

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Anna Meiliana

2011-12-01

Full Text Available BACKGROUND: Increasing prevalence of obesity gives rise to many problems associated with multiple morbidities, such as diabetes, hypertension, heart disease, sleep apnea and cancer. The mechanism of obesity is very complex, thus its link to various disease is poorly understood. This review highlights important concepts in our understanding of the pathogenesis of obesity and related complications. CONTENT: Many studies have tried to explore the exciting and puzzling links between metabolic homeostasis and inflammatory responses. A form of subclinical, low-grade systemic inflammation is known to be associated with both obesity and chronic disease. This, later called as "metaflammation", refers to metabolically triggered inflammation. The nutrient-sensing pathway and the immune response coordination are facilitated by these molecular sites in order to maintain homeostasis under diverse metabolic and immune conditions. Recent studies have found that the NLRP3 inflammasome during metabolic stress forms a tie linking TXNIP, oxidative stress, and IL-1β production. This provides new opportunities for research and therapy for the disease often described as the next global pandemic: type 2 diabetes mellitus (T2DM. SUMMARY: The crucial role of metaflammation in many complications of obesity shown by the unexpected overlap between inflammatory and metabolic sensors and their downstream tissue responses. Then great interest arose to explore the pathways that integrate nutrient and pathogen sensing, give more understanding in the mechanisms of insulin resistance type 2 diabetes, and other chronic metabolic pathologies. A family of intracellular sensors called NLR family is a critical component of the innate immune system. They can form multiprotein complexes, called inflammasome which is capable of responding to a wide range of stimuli including both microbial and self molecules by activating the cysteine protease caspase-1, leading to processing and

Sphingolipid metabolism diseases.

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Kolter, Thomas; Sandhoff, Konrad

2006-12-01

Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated "cross correction", gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT.

Urinary Metabolic Phenotyping Reveals Differences in the Metabolic Status of Healthy and Inflammatory Bowel Disease (IBD Children in Relation to Growth and Disease Activity

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Francois-Pierre Martin

2016-08-01

Full Text Available Background: Growth failure and delayed puberty are well known features of children and adolescents with inflammatory bowel disease (IBD, in addition to the chronic course of the disease. Urinary metabonomics was applied in order to better understand metabolic changes between healthy and IBD children. Methods: 21 Pediatric patients with IBD (mean age 14.8 years, 8 males were enrolled from the Pediatric Gastroenterology Outpatient Clinic over two years. Clinical and biological data were collected at baseline, 6, and 12 months. 27 healthy children (mean age 12.9 years, 16 males were assessed at baseline. Urine samples were collected at each visit and subjected to 1H Nuclear Magnetic Resonance (NMR spectroscopy. Results: Using 1H NMR metabonomics, we determined that urine metabolic profiles of IBD children differ significantly from healthy controls. Metabolic differences include central energy metabolism, amino acid, and gut microbial metabolic pathways. The analysis described that combined urinary urea and phenylacetylglutamine—two readouts of nitrogen metabolism—may be relevant to monitor metabolic status in the course of disease. Conclusion: Non-invasive sampling of urine followed by metabonomic profiling can elucidate and monitor the metabolic status of children in relation to disease status. Further developments of omic-approaches in pediatric research might deliver novel nutritional and metabolic hypotheses.

Metabolic Diseases of Muscle

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... here and still get the great care and treatment I received in Michigan.” MDA Is Here to Help You T he Muscular Dystrophy Association offers a vast array of services to help you and your family deal with metabolic diseases of muscle. The staff at your local MDA office is ...

Abdominal ultrasonography in inheredited diseases of carbohydrate metabolism

International Nuclear Information System (INIS)

Pozzato, Carlo; Curti, Alessandra; Cornalba, Gianpaolo; Radaelli, Giovanni; Fiori, Laura; Rossi, Samantha; Riva, Enrica

2005-01-01

Purpose: To determine the usefulness of abdominal sonography in inherited diseases of carbohydrate metabolism. Materials and methods: Thirty patients (age range, 4 months to 27 years) with glycogen storage diseases, galactosemia, disorders of fructose metabolism were studied with sonography. Echogenicity of the liver, sonographic dimensions of liver, kidneys and spleen were evaluated. Plasma blood parameters (ALT, AST, total cholesterol, triglycerides) were determined. Results: Liver was enlarged in 21/22 patients (95.4%) with glycogen storage diseases, in both subjects with disorders of fructose metabolism, and in 2/6 patients (33.3%) with galactosemia. Hepatic echogenicity was increased in 20/22 patients (90.9%) with glycogen storage diseases, and in the subject with hereditary fructose intolerance. Patients with galactosemia did not show increased liver echogenicity. Both kidney were enlarged in 8/17 patients (47.0%) with glycogen storage disease type I. Subjects with increased hepatic echogenicity exhibited higher plasma concentrations of any blood parameter than the others with normal echogenicity (p [it

Biochemical markers of psoriasis as a metabolic disease

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Agnieszka Gerkowicz

2012-07-01

Full Text Available Psoriasis is a chronic immune mediated inflammatory skin disease with a population prevalence of 2–3%. In recent years, psoriasis has been recognized as a systemic disease associated with metabolic syndrome or its components such as: obesity, insulin resistance, hypertension and atherogenic dyslipidemia. Many bioactive substances have appeared to be related to metabolic syndrome. Based on current literature, we here discuss the possible role of adiponectin, leptin, ghrelin, resistin, inflammatory cytokines, plasminogen activator inhibitor 1, uric acid, C-reactive protein and lipid abnormalities in psoriasis and in metabolic syndrome.

Exercise-induced myokines in health and metabolic diseases

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Byunghun So

2014-12-01

Full Text Available Skeletal muscle has been emerging as a research field since the past 2 decades. Contraction of a muscle, which acts as a secretory organ, stimulates production, secretion, and expression of cytokines or other muscle fiber-derived peptides, i.e., myokines. Exercise-induced myokines influence crosstalk between different organs in an autocrine, endocrine, or paracrine fashion. Myokines are recently recognized as potential candidates for treating metabolic diseases through their ability to stimulate AMP-activated protein kinase signaling, increase glucose uptake, and improve lipolysis. Myokines may have positive effects on metabolic disorders, type 2 diabetes, or obesity. Numerous studies on myokines suggested that myokines offer a potential treatment option for preventing metabolic diseases. This review summarizes the current understanding of the positive effects of exercise-induced myokines, such as interleukin-15, brain-derived neurotrophic factor, leukemia inhibitory factor, irisin, fibroblast growth factor 21, and secreted protein acidic and rich in cysteine, on metabolic diseases.

[Metabolic bone disease osteomalacia].

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Reuss-Borst, M A

2014-05-01

Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.

The Metabolic Role of Gut Microbiota in the Development of Nonalcoholic Fatty Liver Disease and Cardiovascular Disease

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Marco Sanduzzi Zamparelli

2016-07-01

Full Text Available The prevalence of metabolic disorders, such as type 2 diabetes (T2D, obesity, and non-alcoholic fatty liver disease (NAFLD, which are common risk factors for cardiovascular disease (CVD, has dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.

Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases

DEFF Research Database (Denmark)

Goettsch, Claudia; Kjølby, Mads Fuglsang; Aikawa, Elena

2018-01-01

Cardiovascular disease is a leading cause of morbidity and mortality in the Western world. Studies of sortilin's influence on cardiovascular and metabolic diseases goes far beyond the genome-wide association studies that have revealed an association between cardiovascular diseases and the 1p13...... locus that encodes sortilin. Emerging evidence suggests a significant role of sortilin in the pathogenesis of vascular and metabolic diseases; this includes type II diabetes mellitus via regulation of insulin resistance, atherosclerosis through arterial wall inflammation and calcification...... of sortilin's contributions to cardiovascular and metabolic diseases but focuses particularly on atherosclerosis. We summarize recent clinical findings that suggest that sortilin may be a cardiovascular risk biomarker and also discuss sortilin as a potential drug target....

BioM2MetDisease: a manually curated database for associations between microRNAs, metabolites, small molecules and metabolic diseases.

Science.gov (United States)

Xu, Yanjun; Yang, Haixiu; Wu, Tan; Dong, Qun; Sun, Zeguo; Shang, Desi; Li, Feng; Xu, Yingqi; Su, Fei; Liu, Siyao; Zhang, Yunpeng; Li, Xia

2017-01-01

BioM2MetDisease is a manually curated database that aims to provide a comprehensive and experimentally supported resource of associations between metabolic diseases and various biomolecules. Recently, metabolic diseases such as diabetes have become one of the leading threats to people’s health. Metabolic disease associated with alterations of multiple types of biomolecules such as miRNAs and metabolites. An integrated and high-quality data source that collection of metabolic disease associated biomolecules is essential for exploring the underlying molecular mechanisms and discovering novel therapeutics. Here, we developed the BioM2MetDisease database, which currently documents 2681 entries of relationships between 1147 biomolecules (miRNAs, metabolites and small molecules/drugs) and 78 metabolic diseases across 14 species. Each entry includes biomolecule category, species, biomolecule name, disease name, dysregulation pattern, experimental technique, a brief description of metabolic disease-biomolecule relationships, the reference, additional annotation information etc. BioM2MetDisease provides a user-friendly interface to explore and retrieve all data conveniently. A submission page was also offered for researchers to submit new associations between biomolecules and metabolic diseases. BioM2MetDisease provides a comprehensive resource for studying biology molecules act in metabolic diseases, and it is helpful for understanding the molecular mechanisms and developing novel therapeutics for metabolic diseases. http://www.bio-bigdata.com/BioM2MetDisease/. © The Author(s) 2017. Published by Oxford University Press.

Cardiorenal metabolic syndrome in the African diaspora: rationale for including chronic kidney disease in the metabolic syndrome definition.

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Lea, Janice P; Greene, Eddie L; Nicholas, Susanne B; Agodoa, Lawrence; Norris, Keith C

2009-01-01

Chronic kidney disease (CKD) is more likely to progress to end-stage renal disease (ESRD) in African Americans while the reasons for this are unclear. The metabolic syndrome is a risk factor for the development of diabetes, cardiovascular disease, and has been recently linked to incident CKD. Historically, fewer African Americans meet criteria for the definition of metabolic syndrome, despite having higher rates of cardiovascular mortality than Caucasians. The presence of microalbuminuria portends increased cardiovascular risks and has been shown to cluster with the metabolic syndrome. We recently reported that proteinuria is a predictor of CKD progression in African American hypertensives with metabolic syndrome. In this review we explore the potential value of including CKD markers--microalbuminuria/proteinuria or low glomerular filtration rate (GFR)-in refining the cluster of factors defined as metabolic syndrome, ie, "cardiorenal metabolic syndrome."

Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

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Johan W.E. Jocken

2014-10-01

Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

Semi-quantitative interpretation of the bone scan in metabolic bone disease

Energy Technology Data Exchange (ETDEWEB)

Fogelman, I; Turner, J G; Hay, I D; Boyle, I T [Royal Infirmary, Glasgow (UK). Dept. of Nuclear Medicine; Citrin, D L [Wisconsin Univ., Madison (USA). Dept. of Human Oncology; Bessent, G R

1979-01-01

Certain easily recognisable features are commonly seen in the bone scans of patients with metabolic bone disorders. Seven such features have been numerically graded by three independent observers in the scans of 100 patients with metabolic bone disease and of 50 control subjects. The total score for each patient is defined as the metabolic index. The mean metabolic index for each group of patients with metabolic bone disease is significantly greater than that for the control group (P < 0.001). (orig.).

metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research.

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Lyne, Mike; Smith, Richard N; Lyne, Rachel; Aleksic, Jelena; Hu, Fengyuan; Kalderimis, Alex; Stepan, Radek; Micklem, Gos

2013-01-01

Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first

Interrelationship of canonical and non-canonical Wnt signalling pathways in chronic metabolic diseases.

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Ackers, Ian; Malgor, Ramiro

2018-01-01

Chronic diseases account for approximately 45% of all deaths in developed countries and are particularly prevalent in countries with the most sophisticated and robust public health systems. Chronic metabolic diseases, specifically lifestyle-related diseases pertaining to diet and exercise, continue to be difficult to treat clinically. The most prevalent of these chronic metabolic diseases include obesity, diabetes, non-alcoholic fatty liver disease, chronic kidney disease and cardiovascular disease and will be the focus of this review. Wnt proteins are highly conserved glycoproteins best known for their role in development and homeostasis of tissues. Given the importance of Wnt signalling in homeostasis, aberrant Wnt signalling likely regulates metabolic processes and may contribute to the development of chronic metabolic diseases. Expression of Wnt proteins and dysfunctional Wnt signalling has been reported in multiple chronic diseases. It is interesting to speculate about an interrelationship between the Wnt signalling pathways as a potential pathological mechanism in chronic metabolic diseases. The aim of this review is to summarize reported findings on the contrasting roles of Wnt signalling in lifestyle-related chronic metabolic diseases; specifically, the contribution of Wnt signalling to lipid accumulation, fibrosis and chronic low-grade inflammation.

INFORMATION SYSTEM FOR REGISTRY OF PATIENTS WITH METABOLIC DISEASES

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N. H. Horovenko

2015-05-01

Full Text Available This article describes the problems encountered in the management of medical records of patients with metabolic diseases, and also provides a general solution to these problems through the introduction of a software product. Objective was to reduce the burden on the healthcare registrars and medical genetics center, improving the speed and quality of patient care. In the software implementation the main features of the complex design problems are described: the programming language Java, IDE NetBeans, MySQL database server and web application to work with database server phpMyAdmin and put forward requirements. Also, medical receptionist is able to keep track of patients to form an extract, view statistics. During development were numerous consultations with experienced doctors, medical registrars. With the convenient architecture in the future will be easy to add custom modules in the program. Development of the program management of electronic medical records of patients the center of metabolic diseases is essential, because today in Ukraine all the software that can keep track of patients who did not drawn enough attention to patients with metabolic diseases. Currently the software is installed in the center of metabolic diseases NCSH “OKHMATDYT.”

Inflammation meets metabolic disease: Gut feeling mediated by GLP-1

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Tamara eZietek

2016-04-01

Full Text Available Chronic diseases such as obesity and diabetes, cardiovascular and inflammatory bowel diseases (IBD share common features in their pathology. Metabolic disorders exhibit strong inflammatory underpinnings and vice versa, inflammation is associated with metabolic alterations. Next to cytokines and cellular stress pathways like the unfolded protein response (UPR, alterations in the enteroendocrine system are intersections of various pathologies. Enteroendocrine cells (EEC have been studied extensively for their ability to regulate gastrointestinal motility, secretion, and insulin release by release of peptide hormones. In particular the L cell-derived incretin hormone glucagon-like peptide 1 (GLP-1 has gained enormous attention due to its insulinotropic action and relevance in the treatment of type 2 diabetes (T2D. Yet, accumulating data indicates a critical role for EEC and in particular for GLP-1 in metabolic adaptation and in orchestrating immune responses beyond blood glucose control. EEC sense the lamina propria and luminal environment including the microbiota via receptors and transporters. Subsequently mediating signals by secreting hormones and cytokines, EEC can be considered as integrators of metabolic and inflammatory signaling.This review focuses on L cell and GLP-1 functions in the context of metabolic and inflammatory diseases. The effects of incretin-based therapies on metabolism and immune system are discussed and the interrelation and common features of metabolic and immune-mediated disorders are highlighted. Moreover, it presents data on the impact of inflammation, in particular of IBD on EEC and discusses the potential role of the microbiota as link between nutrients, metabolism, immunity and disease.

A clinical perspective of obesity, metabolic syndrome and cardiovascular disease

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Thang S Han

2016-02-01

Full Text Available The metabolic syndrome is a condition characterized by a special constellation of reversible major risk factors for cardiovascular disease and type 2 diabetes. The main, diagnostic, components are reduced HDL-cholesterol, raised triglycerides, blood pressure and fasting plasma glucose, all of which are related to weight gain, specifically intra-abdominal/ectopic fat accumulation and a large waist circumference. Using internationally adopted arbitrary cut-off values for waist circumference, having metabolic syndrome doubles the risk of cardiovascular disease, but offers an effective treatment approach through weight management. Metabolic syndrome now affects 30–40% of people by age 65, driven mainly by adult weight gain, and by a genetic or epigenetic predisposition to intra-abdominal/ectopic fat accumulation related to poor intra-uterine growth. Metabolic syndrome is also promoted by a lack of subcutaneous adipose tissue, low skeletal muscle mass and anti-retroviral drugs. Reducing weight by 5–10%, by diet and exercise, with or without, anti-obesity drugs, substantially lowers all metabolic syndrome components, and risk of type 2 diabetes and cardiovascular disease. Other cardiovascular disease risk factors such as smoking should be corrected as a priority. Anti-diabetic agents which improve insulin resistance and reduce blood pressure, lipids and weight should be preferred for diabetic patients with metabolic syndrome. Bariatric surgery offers an alternative treatment for those with BMI ≥ 40 or 35–40 kg/m 2 with other significant co-morbidity. The prevalence of the metabolic syndrome and cardiovascular disease is expected to rise along with the global obesity epidemic: greater emphasis should be given to effective early weight-management to reduce risk in pre-symptomatic individuals with large waists.

Apolipoprotein M in lipid metabolism and cardiometabolic diseases

DEFF Research Database (Denmark)

Borup, Anna; Christensen, Pernille Meyer; Nielsen, Lars B.

2015-01-01

: The apoM/S1P axis and its implications in atherosclerosis and lipid metabolism have been thoroughly studied. Owing to the discovery of the apoM/S1P axis, the scope of apoM research has broadened. ApoM and S1P have been implicated in lipid metabolism, that is by modulating HDL particles. Also......PURPOSE: This review will address recent findings on apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) in lipid metabolism and inflammatory diseases. RECENT FINDINGS: ApoM's likely role(s) in health and disease has become more diverse after the discovery that apoM functions...... as a chaperone for S1P. Hence, apoM has recently been implicated in lipid metabolism, diabetes and rheumatoid arthritis through in-vivo, in-vitro and genetic association studies. It remains to be established to which degree such associations with apoM can be attributed to its ability to bind S1P. SUMMARY...

Metabolic syndrome in patients with ischemic heart disease

International Nuclear Information System (INIS)

Yasmin, S.; Naveed, T.; Shakoor, T.

2008-01-01

To determine the frequency of metabolic syndrome in patients with Ischemic Heart Disease (IHD). Cross-sectional, descriptive study. A total of 100 subjects with ischemic heart disease, fulfilling the inclusion criteria, were enrolled in the study. Demographic data (age and gender) and the 5 component conditions of the metabolic syndrome were noted. Subjects were physically assessed for the abdominal obesity, based on waist circumference. Fasting blood samples for glucose and lipid profile in first 24 hours after acute coronary insult were drawn and tested in central laboratory. Variables were processed for descriptive statistics. In this study population, 68% were male and 32% were female with mean age of 52 +-13.6 years in men and 56 +- 12.5 years in women. Frequency of metabolic syndrome was 32% in men and 28% in women. It increased with age. The highest rate of metabolic syndrome was in men diagnosed as STEMI (odds ratio: 3.39, 95% CI=1.36-8.41). Frequency of metabolic syndrome was high among the patients with IHD. It supports the potential for preventive efforts in persons with high-risk of IHD. (author)

Celiac disease: A missed cause of metabolic bone disease

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Ashu Rastogi

2012-01-01

Full Text Available Introduction: Celiac disease (CD is a highly prevalent autoimmune disease. The symptoms of CD are varied and atypical, with many patients having no gastrointestinal symptoms. Metabolic bone disease (MBD is a less recognized manifestation of CD associated with spectrum of musculoskeletal signs and symptoms, viz. bone pains, proximal muscle weakness, osteopenia, osteoporosis, and fracture. We here report five patients who presented with severe MBD as the only manifestation of CD. Materials and Methods: Records of 825 patients of CD diagnosed during 2002-2010 were retrospectively analyzed for clinical features, risk factors, signs, biochemical, and radiological parameters. Results: We were able to identify five patients (0.6% of CD who had monosymptomatic presentation with musculoskeletal symptoms and signs in the form of bone pains, proximal myopathy, and fragility fractures without any gastrointestinal manifestation. All the five patients had severe MBD in the form of osteopenia, osteoporosis, and fragility fractures. Four of the five patients had additional risk factors such as antiepileptic drugs, chronic alcohol consumption, malnutrition, and associated vitamin D deficiency which might have contributed to the severity of MBD. Conclusion: Severe metabolic disease as the only presentation of CD is rare. Patients show significant improvement in clinical, biochemical, and radiological parameters with gluten-free diet, calcium, and vitamin D supplementation. CD should be looked for routinely in patients presenting with unexplained MBD.

Skeletal scintigraphy and quantitative tracer studies in metabolic bone disease

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Fogelman, Ignac

Bone scan imaging with the current bone seeking radiopharmaceuticals, the technetium-99m labelled diphosphonates, has dramatically improved our ability to evaluate skeletal pathology. In this thesis, chapter 1 presents a review of the history of bone scanning, summarises present concepts as to the mechanism of uptake of bone seeking agents and briefly illustrates the role of bone scanning in clinical practice. In chapter 2 the applications of bone scan imaging and quantitative tracer techniques derived from the bone scan in the detection of metabolic bone disease are discussed. Since skeletal uptake of Tc-99m diphosphonate depends upon skeletal metabolism one might expect that the bone scan would be of considerable value in the assessment of metabolic bone disease. However in these disorders the whole skeleton is often diffusely involved by the metabolic process and simple visual inspection of the scan image may not reveal the uniformly increased uptake of tracer. Certain patterns of bone scan abnormality have, however, been reported in patients with primary hyperparathyroidism and renal osteo-dystrophy; the present studies extend these observations and introduce the concept of "metabolic features" which are often recognisable in conditions with generalised increased bone turnover. As an aid to systematic recognition of these features on a given bone scan image a semi-quantitative scoring system, the metabolic index, was introduced. The metabolic index allowed differentiation between various groups of patients with metabolic disorders and a control population. In addition, in a bone scan study of patients with acromegaly, it was found that the metabolic index correlated well with disease activity as measured by serum growth hormone levels. The metabolic index was, however, found to be a relatively insensitive means of identifying disease in individual patients. Patients with increased bone turnover will have an absolute increase in skeletal uptake of tracer. As a

Genome-scale metabolic models applied to human health and disease.

Science.gov (United States)

Cook, Daniel J; Nielsen, Jens

2017-11-01

Advances in genome sequencing, high throughput measurement of gene and protein expression levels, data accessibility, and computational power have allowed genome-scale metabolic models (GEMs) to become a useful tool for understanding metabolic alterations associated with many different diseases. Despite the proven utility of GEMs, researchers confront multiple challenges in the use of GEMs, their application to human health and disease, and their construction and simulation in an organ-specific and disease-specific manner. Several approaches that researchers are taking to address these challenges include using proteomic and transcriptomic-informed methods to build GEMs for individual organs, diseases, and patients and using constraints on model behavior during simulation to match observed metabolic fluxes. We review the challenges facing researchers in the use of GEMs, review the approaches used to address these challenges, and describe advances that are on the horizon and could lead to a better understanding of human metabolism. WIREs Syst Biol Med 2017, 9:e1393. doi: 10.1002/wsbm.1393 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Occult Metabolic Bone Disease in Chronic Pancreatitis

African Journals Online (AJOL)

2017-10-26

Oct 26, 2017 ... KEYWORDS: Chronic pancreatitis, metabolic bone disease, osteomalacia, osteopenia ... with malabsorption, and endocrine dysfunction results in diabetes .... of insufficiency and deficiency were not assessed separately due ...

Metabolic Imaging in Parkinson Disease.

Science.gov (United States)

Meles, Sanne K; Teune, Laura K; de Jong, Bauke M; Dierckx, Rudi A; Leenders, Klaus L

2017-01-01

This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Relative Handgrip Strength Is Inversely Associated with Metabolic Profile and Metabolic Disease in the General Population in China.

Science.gov (United States)

Li, Dongxue; Guo, Guanghong; Xia, Lili; Yang, Xinghua; Zhang, Biao; Liu, Feng; Ma, Jingang; Hu, Zhiping; Li, Yajun; Li, Wei; Jiang, Jiajia; Gaisano, Herbert; Shan, Guangliang; He, Yan

2018-01-01

Background: Absolute handgrip strength has been correlated with metabolic profile and metabolic disease. Whether relative handgrip strength is also associated with metabolic disease has not been assessed. This study aimed at assessing the association of relative handgrip strength with metabolic profile and metabolic disease in the general population in China. Methods: Data were derived from an ongoing cross-sectional survey of the 2013 National Physical and Health in Shanxi Province, which involved 5520 participants. Multiple linear regression or multiple logistic regression analysis were used to assess the association of absolute/relative handgrip strength with the metabolic profile, preclinical, and established stages of metabolic diseases. Results: This study revealed that relative handgrip strength, that is when normalized to BMI, was associated with: (1) in both genders for more favorable blood lipid levels of high-density lipoprotein cholesterol [males: b = 0.19 (0.15, 0.23); females: b = 0.22 (0.17, 0.28)], low-density lipoprotein cholesterol [males: b = -0.14 (-0.23, -0.05); females: b = -0.19 (-0.31, -0.18)], triglycerides [males: b = -0.58 (-0.74, -0.43); females: b = -0.55 (-0.74, -0.36)] and total cholesterol [males: b = -0.20 (-0.31, -0.10); females: b = -0.19 (-0.32, -0.06)]; and better serum glucose levels in males [ b = -0.30 (-0.46, -0.15)]. (2) lower risk of impaired fasting glucose in males {third quartile [OR = 0.66 (0.45-0.95)] and fourth quartile [OR = 0.46 (0.30-0.71)] vs. first quartile} and dyslipidemia in both genders {third quartile [males: OR = 0.65 (0.48-0.87); females: OR = 0.68 (0.53-0.86)] and fourth quartile [males: OR = 0.47 (0.35-0.64); females: OR = 0.47(0.36-0.61)] vs. first quartile}. (3) lower risk of hyperlipidemia in both genders third quartile [males: OR = 0.66 (0.50-0.87); females: OR = 0.57 (0.43-0.75)] and fourth quartile [males: OR = 0.35 (0.26-0.47); females: OR = 0.51 (0.38-0.70)] vs. first quartile. However, contrary

A simple method of screening for metabolic bone disease

International Nuclear Information System (INIS)

Broughton, R.B.K.; Evans, W.D.

1982-01-01

The purpose of this investigation was to find a simple method -to be used as an adjunct to the conventional bone scintigram- that could differentiate between decreased bone metabolism or mass, i.e., osteoporosis -normal bone- and the group of conditions of increased bone metabolism or mass namely, osteomalacia, renal osteodystrophy, hyperparathyroidism and Paget's disease. The Fogelman's method using the bone to soft tissue ratios from region of interest analysis at 4 hours post injection, was adopted. An initial experience in measuring a value for the count rate density in lumbar vertebrae at 1 hr post injection during conventional bone scintigraphy appears to give a clear indication of the overall rate of bone metabolism. The advantage over whole body retention methods is that the scan performed at the end of the metabolic study will reveal localized bone disease that may otherwise not be anticipated

Cerebral glucose metabolism in Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Martin, W R.W.; Beckman, J H; Calne, D B; Adam, M J; Harrop, R; Rogers, J G; Ruth, T J; Sayre, C I; Pate, B D [British Columbia Univ., Vancouver (Canada). TRIUMF Facility

1984-02-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

Cerebral glucose metabolism in Parkinson's disease

International Nuclear Information System (INIS)

Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

1984-01-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

Prevention of metabolic diseases: fruits (including fruit sugars) vs. vegetables.

Science.gov (United States)

Kuzma, Jessica N; Schmidt, Kelsey A; Kratz, Mario

2017-07-01

To discuss recent evidence from observational and intervention studies on the relationship between fruit and vegetable (F&V) consumption and metabolic disease. Observational studies have consistently demonstrated a modest inverse association between the intake of fruit and leafy green vegetables, but not total vegetables, and biomarkers of metabolic disease as well as incident type 2 diabetes mellitus. This is in contrast to limited evidence from recently published randomized controlled dietary intervention trials, which - in sum - suggests little to no impact of increased F&V consumption on biomarkers of metabolic disease. Evidence from observational studies that fruit and leafy green vegetable intake is associated with lower type 2 diabetes risk and better metabolic health could not be confirmed by dietary intervention trials. It is unclear whether this discrepancy is because of limitations inherent in observational studies (e.g., subjective dietary assessment methods, residual confounding) or due to limitations in the few available intervention studies (e.g., short duration of follow-up, interventions combining whole fruit and fruit juice, or lack of compliance). Future studies that attempt to address these limitations are needed to provide more conclusive insight into the impact of F&V consumption on metabolic health.

MECHANISMS IN ENDOCRINOLOGY: The sexually dimorphic role of androgens in human metabolic disease.

Science.gov (United States)

Schiffer, Lina; Kempegowda, Punith; Arlt, Wiebke; O'Reilly, Michael W

2017-09-01

Female androgen excess and male androgen deficiency manifest with an overlapping adverse metabolic phenotype, including abdominal obesity, insulin resistance, type 2 diabetes mellitus, non-alcoholic fatty liver disease and an increased risk of cardiovascular disease. Here, we review the impact of androgens on metabolic target tissues in an attempt to unravel the complex mechanistic links with metabolic dysfunction; we also evaluate clinical studies examining the associations between metabolic disease and disorders of androgen metabolism in men and women. We conceptualise that an equilibrium between androgen effects on adipose tissue and skeletal muscle underpins the metabolic phenotype observed in female androgen excess and male androgen deficiency. Androgens induce adipose tissue dysfunction, with effects on lipid metabolism, insulin resistance and fat mass expansion, while anabolic effects on skeletal muscle may confer metabolic benefits. We hypothesise that serum androgen concentrations observed in female androgen excess and male hypogonadism are metabolically disadvantageous, promoting adipose and liver lipid accumulation, central fat mass expansion and insulin resistance. © 2017 The authors.

Exploring metabolic dysfunction in chronic kidney disease

Directory of Open Access Journals (Sweden)

Slee Adrian D

2012-04-01

Full Text Available Abstract Impaired kidney function and chronic kidney disease (CKD leading to kidney failure and end-stage renal disease (ESRD is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS, with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid

Chylomicrons metabolism in patients with coronary artery disease

International Nuclear Information System (INIS)

Brandizzi, Laura Ines Ventura

2002-01-01

Chylomicrons are the triglyceride-rich lipoproteins that carry dietary lipids absorbed in the intestine. In the bloodstream , chylomicron triglycerides are broken-down by lipoprotein lipase using apoliprotein (apo) CII as co factor. Fatty acids and glycerol resulting from the enzymatic action are absorbed and stored in the body tissues mainly adipose and muscle for subsequent utilizations energy source. The resulting triglycerides depleted remnants are taken-up by liver receptor such as the LDL receptor using mainly apo E as ligand. For methodological reasons, chylomicron metabolism has been unfrequently studied in subjects despite its pathophysiological importance, and this metabolism was not evaluated in the great clinical trials that established the link between atherosclerosis and lipids. In studies using oral fat load tests, it has been shown that in patients with coronary artery disease there is a trend to accumulation of post-prandial triglycerides, vitamin A or apo B-48 , suggesting that in those patients chylomicrons and their remnants are slowly removed from the circulation. A triglyceride-rich emulsion marked radioisotopic which mimics chylomicron metabolism when injected into the bloodstream has been described that can offer a more straight forward approach to evaluate chylomicrons. In coronary artery disease patients both lipolysis and remnant removal from the plasma of the chylomicron-like emulsions were found slowed-down compared with control subjects without the disease. The introduction of more practical techniques to assess chylomicron metabolism may be new mechanisms underlying atherogenesis. (author)

Relative Handgrip Strength Is Inversely Associated with Metabolic Profile and Metabolic Disease in the General Population in China

Directory of Open Access Journals (Sweden)

Dongxue Li

2018-02-01

Full Text Available Background: Absolute handgrip strength has been correlated with metabolic profile and metabolic disease. Whether relative handgrip strength is also associated with metabolic disease has not been assessed. This study aimed at assessing the association of relative handgrip strength with metabolic profile and metabolic disease in the general population in China.Methods: Data were derived from an ongoing cross-sectional survey of the 2013 National Physical and Health in Shanxi Province, which involved 5520 participants. Multiple linear regression or multiple logistic regression analysis were used to assess the association of absolute/relative handgrip strength with the metabolic profile, preclinical, and established stages of metabolic diseases.Results: This study revealed that relative handgrip strength, that is when normalized to BMI, was associated with: (1 in both genders for more favorable blood lipid levels of high-density lipoprotein cholesterol [males: b = 0.19 (0.15, 0.23; females: b = 0.22 (0.17, 0.28], low-density lipoprotein cholesterol [males: b = −0.14 (−0.23, −0.05; females: b = −0.19 (−0.31, −0.18], triglycerides [males: b = −0.58 (−0.74, −0.43; females: b = −0.55 (−0.74, −0.36] and total cholesterol [males: b = −0.20 (−0.31, −0.10; females: b = −0.19 (−0.32, −0.06]; and better serum glucose levels in males [b = −0.30 (−0.46, −0.15]. (2 lower risk of impaired fasting glucose in males {third quartile [OR = 0.66 (0.45–0.95] and fourth quartile [OR = 0.46 (0.30–0.71] vs. first quartile} and dyslipidemia in both genders {third quartile [males: OR = 0.65 (0.48–0.87; females: OR = 0.68 (0.53–0.86] and fourth quartile [males: OR = 0.47 (0.35–0.64; females: OR = 0.47(0.36–0.61] vs. first quartile}. (3 lower risk of hyperlipidemia in both genders third quartile [males: OR = 0.66 (0.50–0.87; females: OR = 0.57 (0.43–0.75] and fourth quartile [males: OR = 0.35 (0.26–0.47; females: OR

Metabolism features in the active rheumatoid disease

Energy Technology Data Exchange (ETDEWEB)

Cossermelli, W; Carvalho, N; Papaleo Netto, M [Sao Paulo Univ. (Brazil). Centro de Medicina Nuclear

1974-02-01

The /sup 131/I-labelled albumin metabolism was studied in fourteen female patients with rheumatoid arthritis. The half-life of distribution was increased while the turnover half-life and turnover rate was within normal limits. These results led to assume that synthesis and catabolism may not change this disease, not being the responsible mechanism of hypoalbuminemia. Hypoalbuminemia would appear as compensatory mechanism in view of other protein alterations, as hypergammaglobulinemia, without changes of stabilizing and metabolic properties of albumin, perhaps due to albumin molecular alterations.

Reappraisal of GIP Pharmacology for Metabolic Diseases

DEFF Research Database (Denmark)

Finan, Brian; Müller, Timo D; Clemmensen, Christoffer

2016-01-01

Glucagon-like peptide-1 (GLP-1) analogs are considered the best current medicines for type 2 diabetes (T2D) and obesity due to their actions in lowering blood glucose and body weight. Despite similarities to GLP-1, glucose-dependent insulinotropic polypeptide (GIP) has not been extensively pursue...... be beneficial for metabolic diseases. However, a growing body of new evidence - including data based on refined genetically modified models and improved pharmacological agents - suggests a paradigm shift on how the GIP system should be manipulated for metabolic benefits....

Metabolism features in the active rheumatoid disease

International Nuclear Information System (INIS)

Cossermelli, W.; Carvalho, N.; Papaleo Netto, M.

1974-01-01

It was studied the 131 I-labelled albumin metabolism in fourteen female patients with rheumatoid arthritis. The half-life of distribution was increased while the turnover half-life and turnover rate was within normal limits. These results led to assume that synthesis and catabolism may not change this disease, not being the responsible mechanism of hypoalbuminemia. Hypoalbuminemia would appear as compensatory mechanism in view of other protein alterations, as hypergammaglobulinemia, without changes of stabilizing and metabolic properties of albumin, perhaps due to albumin molecular alterations [pt

Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease.

Science.gov (United States)

Gu, Xue-Mei; Huang, Han-Chang; Jiang, Zhao-Feng

2012-10-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathology of AD includes amyloid-β (Aβ) deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau, as well as neuronal loss in specific brain regions. Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease. Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ, accumulation of which might interfere with the homeostasis of cellular metabolism. Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis. Mitochondrial dysfunction might contribute to Aβ neurotoxicity. In this review, we summarize the pathways of Aβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.

Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

Science.gov (United States)

Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

2017-07-01

The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Metabolic disorders and nutritional status in autoimmune thyroid diseases

Directory of Open Access Journals (Sweden)

Anna Kawicka

2015-01-01

Full Text Available In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs are caused by an abnormal immune response to autoantigens present in the thyroid gland – they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto’s disease. Hashimoto’s thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones’ activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient’s body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1 and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium. Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the

[Metabolic disorders and nutritional status in autoimmune thyroid diseases].

Science.gov (United States)

Kawicka, Anna; Regulska-Ilow, Bożena; Regulska-Ilow, Bożena

2015-01-02

In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an abnormal immune response to autoantigens present in the thyroid gland - they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto's disease. Hashimoto's thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones' activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD) also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient's body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1) and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium). Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the relationship of metabolic

Founders lecture 2007. Metabolic bone disease: what has changed in 30 years?

Energy Technology Data Exchange (ETDEWEB)

Sundaram, Murali [Cleveland Clinic, Diagnostic Radiology, MSK, Cleveland, OH (United States)

2009-09-15

To provide an update on imaging of metabolic bone disease based on new developments, findings, and changing practices over the past 30 years. Literature review of osteoporosis, osteomalacia, renal osteodystrophy, Paget's disease, bisphosphonates, with an emphasis on imaging. Cited references and pertinent findings. Significant developments have occurred in the imaging of metabolic bone disease over the past 30 years. (orig.)

Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease

Directory of Open Access Journals (Sweden)

Takashi Himoto

2018-01-01

Full Text Available Zinc (Zn is an essential trace element which has favorable antioxidant, anti-inflammatory, and apoptotic effects. The liver mainly plays a crucial role in maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency causes plenty of metabolic abnormalities, including insulin resistance, hepatic steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency. Recent studies have revealed the putative mechanisms by which Zn deficiency evokes a variety of metabolic abnormalities in chronic liver disease. Zn supplementation has shown beneficial effects on such metabolic abnormalities in experimental models and actual patients with chronic liver disease. This review summarizes the pathogenesis of metabolic abnormalities deriving from Zn deficiency and the favorable effects of Zn administration in patients with chronic liver disease. In addition, we also highlight the interactions between Zn and other trace elements, vitamins, amino acids, or hormones in such patients.

MR imaging of metabolic white matter diseases: Therapeutic response

International Nuclear Information System (INIS)

Gebarski, S.S.; Allen, R.

1987-01-01

In metabolic diseases affecting the brain, MR imaging abnormalities include white-matter signal aberrations suggesting myelination delay, dysmyelination and demyelination, pathologic iron storage, and finally, loss of substance usually in a nonspecific pattern. The authors suggest that MR imaging may have therapeutic implications: (1) classic galactosemia - white-matter signal aberration became normal after dietary therapy; (2) phenylketonuria - age- and sex-matched treated and nontreated adolescents showed marked differences in brain volume, with the treated patient's volume nearly normal; (3) maple syrup urine disease - gross white-matter signal aberration became nearly normal after dietary therapy; and (4) hyperglycinemia - relentless progression of white-matter signal aberration and loss of brain substance despite therapy. These data suggest that brain MR imaging may provide a therapeutic index in certain metabolic diseases

Metabolic effects of obesity causing disease in childhood.

Science.gov (United States)

Abrams, Pamela; Levitt Katz, Lorraine E

2011-02-01

Childhood obesity is rising to epidemic proportions throughout the world, and much emphasis has been placed on the long-term consequences that can result later, in adulthood. This article reviews the metabolic consequences of obesity that can manifest as disease during the childhood years. Obese children suffer from many disease processes once thought to affect only adults. They can have type 2 diabetes mellitus, and potentially early β cell failure with rapid progression to an insulin requirement. There is a high prevalence of fatty liver disease in obese children, and complications such as steatohepatitis and even cirrhosis can develop during childhood. Visceral fat has been shown to have many different properties than subcutaneous fat, and children with central adiposity can develop the metabolic syndrome with insulin resistance, hypertension, and dyslipidemia. Hyperandrogenism, sleep disturbances, and many types of orthopedic complications can also develop in young children. Physicians should not only warn obese children and their families about the long-term consequences of obesity for which they are at risk in adulthood, they should also screen for the many diseases that may already be present.

Impact of the gut microbiota on inflammation, obesity, and metabolic disease.

Science.gov (United States)

Boulangé, Claire L; Neves, Ana Luisa; Chilloux, Julien; Nicholson, Jeremy K; Dumas, Marc-Emmanuel

2016-04-20

The human gut harbors more than 100 trillion microbial cells, which have an essential role in human metabolic regulation via their symbiotic interactions with the host. Altered gut microbial ecosystems have been associated with increased metabolic and immune disorders in animals and humans. Molecular interactions linking the gut microbiota with host energy metabolism, lipid accumulation, and immunity have also been identified. However, the exact mechanisms that link specific variations in the composition of the gut microbiota with the development of obesity and metabolic diseases in humans remain obscure owing to the complex etiology of these pathologies. In this review, we discuss current knowledge about the mechanistic interactions between the gut microbiota, host energy metabolism, and the host immune system in the context of obesity and metabolic disease, with a focus on the importance of the axis that links gut microbes and host metabolic inflammation. Finally, we discuss therapeutic approaches aimed at reshaping the gut microbial ecosystem to regulate obesity and related pathologies, as well as the challenges that remain in this area.

Mechanistic modeling of aberrant energy metabolism in human disease

Directory of Open Access Journals (Sweden)

Vineet eSangar

2012-10-01

Full Text Available Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.

Dietary Treatment of Metabolic Acidosis in Chronic Kidney Disease.

Science.gov (United States)

Siener, Roswitha

2018-04-20

Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid⁻base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables. Alkali therapy of chronic metabolic acidosis can be achieved by providing an alkali-rich diet or oral administration of alkali salts. The primary goal of dietary treatment should be to increase the proportion of fruits and vegetables and to reduce the daily protein intake to 0.8⁻1.0 g per kg body weight. Diet modifications should begin early, i.e., even in patients with moderate kidney impairment, because usual dietary habits of many developed societies contribute an increased proportion of acid equivalents due to the high intake of protein from animal sources.

Dietary Treatment of Metabolic Acidosis in Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

Roswitha Siener

2018-04-01

Full Text Available Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid–base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables. Alkali therapy of chronic metabolic acidosis can be achieved by providing an alkali-rich diet or oral administration of alkali salts. The primary goal of dietary treatment should be to increase the proportion of fruits and vegetables and to reduce the daily protein intake to 0.8–1.0 g per kg body weight. Diet modifications should begin early, i.e., even in patients with moderate kidney impairment, because usual dietary habits of many developed societies contribute an increased proportion of acid equivalents due to the high intake of protein from animal sources.

Nutritional and metabolic diseases involving the nervous system.

Science.gov (United States)

Kopcha, M

1987-03-01

This article will discuss eight diseases that alter normal nervous system function: hypovitaminosis A, water deprivation/salt toxicity, ammonia toxicosis, hypomagnesemia, hypocalcemia, nervous ketosis, hepatoencephalopathy, and rumen metabolic acidosis.

Metabolic Syndrome: Systems Thinking in Heart Disease.

Science.gov (United States)

Dommermuth, Ron; Ewing, Kristine

2018-03-01

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors. MetS is associated with approximately 4-fold increase in the likelihood of developing type 2 diabetes mellitus (T2DM) and a 2-fold increase in the incidence of cardiovascular disease complications. MetS is a progressive, proinflammatory, prothrombotic condition that manifests itself along a broad spectrum of disease. It is associated with hypertension, obstructive sleep apnea, fatty liver disease, gout, and polycystic ovarian syndrome. Intervening in and reversing the pathologic process become more difficult as the disease progresses, highlighting the needs for increased individual and community surveillance and primary prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

Skeletal muscle metabolism during prolonged exercise in Pompe disease

DEFF Research Database (Denmark)

Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt

2017-01-01

OBJECTIVE: Pompe disease (glycogenosis type II) is caused by lysosomal alpha-glucosidase deficiency, which leads to a block in intra-lysosomal glycogen breakdown. In spite of enzyme replacement therapy, Pompe disease continues to be a progressive metabolic myopathy. Considering the health benefits...... of exercise, it is important in Pompe disease to acquire more information about muscle substrate use during exercise. METHODS: Seven adults with Pompe disease were matched to a healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak) and (2) carbohydrate and fatty acid metabolism...... during submaximal exercise (33 W) for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable isotopes. RESULTS: In the patients, VO2peak was less than half of average control values; mean difference -1659 mL/min (CI: -2450 to -867, P = 0.001). However, the respiratory exchange ratio...

Prevalence of non alcoholic fatty liver disease in patients with metabolic syndrome

International Nuclear Information System (INIS)

Iftikhar, R.; Kamran, S.M.

2015-01-01

To determine frequency of Non Alcoholic fatty liver disease in patients with Metabolic Syndrome (MetS). Study Design: Cross sectional study. Place and Duration of Study: Department of medicine, CMH Okara, Jan 2013 to July 2013. Patients and Methods: We included 491 adult males, diagnosed with metabolic syndrome (MetS), presenting in outpatient department for routine review. MetS was diagnosed as per the International Diabetes Federation (IDF) proposed criteria of 2004. Detailed history and examination of each individual was done and data entered in pre designed performa. Brightness and posterior attenuation on ultrasound abdomen were considered indices for fatty liver disease in presence of elevated ALT, negative hepatitis serology and absence of alcohol intake. All the data was analyzed using SPSS version 16. p value of less than 0.05 was considered statistically significant. Results: Out of 491 participants with MetS, 222 (45.2%) had fatty liver disease. Mean BMI in patients with metabolic syndrome was 26.1 (± .89) and mean BMI in fatty liver patients was 27.3 (± 0.67). Out of total 5 components of Mets, patients with fatty liver disease had 3.24 (± 0.25) components, as compared to 2.1 (± 0.34) in whole of study group. Conclusion: A large number of patients with metabolic syndrome have fatty liver disease. Fatty liver disease is more frequent in patients who are overweight and those having multiple risk factors of metabolic syndrome. (author)

Metabolic Bone Disease in the Bariatric Surgery Patient

Directory of Open Access Journals (Sweden)

Susan E. Williams

2011-01-01

Full Text Available Bariatric surgery has proven to be a life-saving measure for some, but for others it has precipitated a plethora of metabolic complications ranging from mild to life-threatening, sometimes to the point of requiring surgical revision. Obesity was previously thought to be bone protective, but this is indeed not the case. Morbidly obese individuals are at risk for metabolic bone disease (MBD due to chronic vitamin D deficiency, inadequate calcium intake, sedentary lifestyle, chronic dieting, underlying chronic diseases, and the use of certain medications used to treat those diseases. After bariatric surgery, the risk for bone-related problems is even greater, owing to severely restricted intake, malabsorption, poor compliance with prescribed supplements, and dramatic weight loss. Patients presenting for bariatric surgery should be evaluated for MBD and receive appropriate presurgical interventions. Furthermore, every patient who has undergone bariatric surgery should receive meticulous lifetime monitoring, as the risk for developing MBD remains ever present.

Differential glucose metabolism in mice and humans affected by McArdle disease

DEFF Research Database (Denmark)

Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L

2016-01-01

McArdle disease (muscle glycogenosis type V) is a disease caused by myophosphorylase deficiency leading to "blocked" glycogen breakdown. A significant but varying glycogen accumulation in especially distal hind limb muscles of mice affected by McArdle disease has recently been demonstrated......, which could lead to lower glycogen accumulation. In comparison, tibialis anterior, extensor digitorum longus, and soleus had massive glycogen accumulation, but few, if any, changes or adaptations in glucose metabolism compared with wild-type mice. The findings suggest plasticity in glycogen metabolism....... In this study, we investigated how myophosphorylase deficiency affects glucose metabolism in hind limb muscle of 20-wk-old McArdle mice and vastus lateralis muscles from patients with McArdle disease. Western blot analysis and activity assay demonstrated that glycogen synthase was inhibited in glycolytic muscle...

The association of serum leptin levels with metabolic diseases

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Jen-Pi Tsai

2017-01-01

Full Text Available Leptin is a 167-amino-acid protein released by white adipose tissue and encoded by the obese gene. It has a role as a negative regulator of appetite control through sending a satiety signal to act on receptors within the hypothalamus. At normal levels, leptin can exert its effects on weight regulation according to white fat mass, induce sodium excretion, maintain vascular tone, and repair the myocardium. Beyond these effects, elevated serum leptin levels have been implicated in the pathogenesis of metabolic syndrome, diabetes mellitus, hypertension, and multiple cardiovascular diseases. In addition, hyperleptinemia had been reported to contribute to renal diseases through multiple mechanisms resulting in glomerulopathy presenting with a decreased glomerular filtration rate, increased albuminuria, and related clinical symptoms, which are pathophysiological features of chronic kidney disease. Because these cardiovascular and metabolic disorders are great challenges for physicians, understanding the related pathophysiological association with leptin might become a valuable aid in handling patients in daily clinical practice. This review will discuss the roles of leptin in the regulation of biological functions of multiple organs beyond the maintenance of feeding and metabolism.

The role of IL6 in liver cancer linked to metabolic liver disease ...

International Development Research Centre (IDRC) Digital Library (Canada)

The role of IL6 in liver cancer linked to metabolic liver disease. Liver cancer is highly fatal, it has very few treatment options, and it is one of the few cancers whose incidence is rising worldwide. One poorly understood risk factor for liver cancer is obesity/metabolic disease (such as diabetes and fatty liver disease).

Krüppel-Like Factors in Metabolic Homeostasis and Cardiometabolic Disease

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Yumiko Oishi

2018-06-01

Full Text Available Members of the Krüppel-like factor (KLF family of transcription factors, which are characterized by the presence of three conserved Cys2/His2 zinc-fingers in their C-terminal domains, control a wide variety of biological processes. In particular, recent studies have revealed that KLFs play diverse and essential roles in the control of metabolism at the cellular, tissue and systemic levels. In both liver and skeletal muscle, KLFs control glucose, lipid and amino acid metabolism so as to coordinate systemic metabolism in the steady state and in the face of metabolic stresses, such as fasting. The functions of KLFs within metabolic tissues are also important contributors to the responses to injury and inflammation within those tissues. KLFs also control the function of immune cells, such as macrophages, which are involved in the inflammatory processes underlying both cardiovascular and metabolic diseases. This review focuses mainly on the physiological and pathological functions of KLFs in the liver and skeletal muscle. The involvement of KLFs in inflammation in these tissues is also summarized. We then discuss the implications of KLFs' control of metabolism and inflammation in cardiometabolic diseases.

Metabolomics reveals metabolic biomarkers of Crohn's disease

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Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

2009-06-01

The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

Metabolic Effects of Obesity and Its Interaction with Endocrine Diseases.

Science.gov (United States)

Clark, Melissa; Hoenig, Margarethe

2016-09-01

Obesity in pet dogs and cats is a significant problem in developed countries, and seems to be increasing in prevalence. Excess body fat has adverse metabolic consequences, including insulin resistance, altered adipokine secretion, changes in metabolic rate, abnormal lipid metabolism, and fat accumulation in visceral organs. Obese cats are predisposed to endocrine and metabolic disorders such as diabetes and hepatic lipidosis. A connection likely also exists between obesity and diabetes mellitus in dogs. No system has been developed to identify obese pets at greatest risk for development of obesity-associated metabolic diseases, and further study in this area is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

The study on risk factor of metabolic diseases in pancreatic steatosis

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Cho, Jin Young; Ye, Soo Young; Kim, Dong Hyun [Dept. of Radiological Science, College of Health Sciences, Catholic University of Pusan, Busan (Korea, Republic of)

2016-03-15

The body of the fat tissue increased in obese represented by risk factors such as cardiovascular diseases, diabetes, metabolic disease and dyslipidemia. Such metabolic diseases and the like of the cardiovascular and cerebrovascular disease, hypertension, dyslipidemia, increase in the adipose tissue of the pancreas is known to be a risk factor of these diseases. Study on the diagnosis and treatment of pancreatic cancer was conducted actively, case studies on pancreatic steatosis is not much. In this study, divided into a control group diagnosed with pancreatic steatosis as a result of ultrasonography to evaluation the physical characteristics and serologic tests and blood pressure and arterial stiffness. The control group and the test pancreas steatosis age and waist circumference, body mass index, total cholesterol, HDL cholesterol, LDL cholesterol, and systolic and diastolic blood pressure, fasting blood glucose, arterial elasticity is higher in pancreatic steatosis. And the lower ankle brachial stenosis and HDLcholesterol were lower than the normal control group, so the pancreatic steatosis harmful to blood vessels.(P <0.05). The difference between the control group and it was confirmed that the pancreatic jibanggun statistically significant. In conclusion, pancreatic steatosis at abdominal ultrasound can predict the risk of metabolic diseases, and there was a correlation with cardiovascular disease.

The study on risk factor of metabolic diseases in pancreatic steatosis

International Nuclear Information System (INIS)

Cho, Jin Young; Ye, Soo Young; Kim, Dong Hyun

2016-01-01

The body of the fat tissue increased in obese represented by risk factors such as cardiovascular diseases, diabetes, metabolic disease and dyslipidemia. Such metabolic diseases and the like of the cardiovascular and cerebrovascular disease, hypertension, dyslipidemia, increase in the adipose tissue of the pancreas is known to be a risk factor of these diseases. Study on the diagnosis and treatment of pancreatic cancer was conducted actively, case studies on pancreatic steatosis is not much. In this study, divided into a control group diagnosed with pancreatic steatosis as a result of ultrasonography to evaluation the physical characteristics and serologic tests and blood pressure and arterial stiffness. The control group and the test pancreas steatosis age and waist circumference, body mass index, total cholesterol, HDL cholesterol, LDL cholesterol, and systolic and diastolic blood pressure, fasting blood glucose, arterial elasticity is higher in pancreatic steatosis. And the lower ankle brachial stenosis and HDLcholesterol were lower than the normal control group, so the pancreatic steatosis harmful to blood vessels.(P <0.05). The difference between the control group and it was confirmed that the pancreatic jibanggun statistically significant. In conclusion, pancreatic steatosis at abdominal ultrasound can predict the risk of metabolic diseases, and there was a correlation with cardiovascular disease

Inherited metabolic liver diseases in infants and children: an overview

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Ivo Barić

2013-10-01

Full Text Available Inborn errors of metabolism, which affect the liver are a large, continuously increasing group of diseases. Their clinical onset can occur at any age, from intrauterine period presenting as liver failure already at birth to late adulthood. Inherited metabolic disorders must be considered in differential diagnosis of every unexplained liver disease. Specific diagnostic work-up for either their confirmation or exclusion should start immediately since any postponing can result in delayed diagnosis and death or irreversible disability. This can be particularly painful while many inherited metabolic liver diseases are relatively easily treatable if diagnosed on time, for instance galactosemia or hereditary fructose intolerance by simple dietary means. Any unexplained liver disease, even one looking initially benign, should be considered as a potential liver failure and therefore should deserve proper attention. Diagnosis in neonates is additionally complicated because of the factors which can mask liver disease, such as physiological neonatal jaundice, normally relatively enlarged liver and increased transaminases at that age. In everyday practice, in order to reveal the etiology, it is useful to classify and distinguish some clinical patterns which, together with a few routine, widely available laboratory tests (aminotransferases, prothrombine time, albumin, gammaGT, total and conjugated bilirubin, ammonia, alkaline phosphatase and glucose make the search for the cause much easier. These patterns are isolated hyperbilirubinemia, syndrome of cholestasis in early infancy, hepatocellular jaundice, Reye syndrome, portal cirrhosis and isolated hepatomegaly. Despite the fact that some diseases can present with more than one pattern (for instance, alpha-1-antitrypsin deficiency as infantile cholestasis, but also as hepatocellular jaundice, and that in some disesases one pattern can evolve into another (for instance, Wilson disease from hepatocellular

Who's your daddy?: paternal inheritance of metabolic disease risk.

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Isganaitis, Elvira; Suehiro, Harumi; Cardona, Connie

2017-02-01

Although the importance of optimizing mothers' health prior to conception and during pregnancy is now well accepted, recent data also implicate health and nutritional status of fathers as contributors to chronic disease risk in their progeny. This brief review will highlight recent epidemiological and experimental studies linking paternal overnutrition, undernutrition, and other forms of stress, to metabolic disease in the offspring. The past 2 years have brought tremendous insights into the mechanisms by which paternal exposures can contribute to disease susceptibility in the next generation. Recent data, both from humans and experimental models, demonstrate that paternal obesity and undernutrition result in epigenetic reprogramming of male germ cells, notably altered DNA methylation, histone retention, and expression of small noncoding RNAs and transfer RNA fragments. Novel mechanisms have also been identified, such as epididymal transport vesicles, seminal fluid hormones and metabolites, and a unique seminal fluid microbiome. Paternal nutritional and other perturbations are linked to risk of metabolic disease and obesity in offspring. Germ cell-dependent mechanisms have recently been linked to these intergenerational effects. Nongenetic, paternal inheritance of chronic disease has important implications for public health, and may provide novel opportunities for multigenerational disease prevention.

Nutrigenetics and Metabolic Disease: Current Status and Implications for Personalised Nutrition

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Phillips, Catherine M.

2013-01-01

Obesity, particularly central adiposity, is the primary causal factor in the development of insulin resistance, the hallmark of the metabolic syndrome (MetS), a common condition characterized by dyslipidaemia and hypertension, which is associated with increased risk of cardiovascular disease (CVD) and type 2 diabetes (T2DM). Interactions between genetic and environmental factors such as diet and lifestyle, particularly over-nutrition and sedentary behavior, promote the progression and pathogenesis of these polygenic diet-related diseases. Their current prevalence is increasing dramatically to epidemic proportions. Nutrition is probably the most important environmental factor that modulates expression of genes involved in metabolic pathways and the variety of phenotypes associated with obesity, the MetS and T2DM. Furthermore, the health effects of nutrients may be modulated by genetic variants. Nutrigenomics and nutrigenetics require an understanding of nutrition, genetics, biochemistry and a range of “omic” technologies to investigate the complex interaction between genetic and environmental factors relevant to metabolic health and disease. These rapidly developing fields of nutritional science hold much promise in improving nutrition for optimal personal and public health. This review presents the current state of the art in nutrigenetic research illustrating the significance of gene-nutrient interactions in the context of metabolic disease. PMID:23306188

Nutrigenetics and Metabolic Disease: Current Status and Implications for Personalised Nutrition

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Catherine M. Phillips

2013-01-01

Full Text Available Obesity, particularly central adiposity, is the primary causal factor in the development of insulin resistance, the hallmark of the metabolic syndrome (MetS, a common condition characterized by dyslipidaemia and hypertension, which is associated with increased risk of cardiovascular disease (CVD and type 2 diabetes (T2DM. Interactions between genetic and environmental factors such as diet and lifestyle, particularly over-nutrition and sedentary behavior, promote the progression and pathogenesis of these polygenic diet-related diseases. Their current prevalence is increasing dramatically to epidemic proportions. Nutrition is probably the most important environmental factor that modulates expression of genes involved in metabolic pathways and the variety of phenotypes associated with obesity, the MetS and T2DM. Furthermore, the health effects of nutrients may be modulated by genetic variants. Nutrigenomics and nutrigenetics require an understanding of nutrition, genetics, biochemistry and a range of “omic” technologies to investigate the complex interaction between genetic and environmental factors relevant to metabolic health and disease. These rapidly developing fields of nutritional science hold much promise in improving nutrition for optimal personal and public health. This review presents the current state of the art in nutrigenetic research illustrating the significance of gene-nutrient interactions in the context of metabolic disease.

Nutrigenetics and metabolic disease: current status and implications for personalised nutrition.

Science.gov (United States)

Phillips, Catherine M

2013-01-10

Obesity, particularly central adiposity, is the primary causal factor in the development of insulin resistance, the hallmark of the metabolic syndrome (MetS), a common condition characterized by dyslipidaemia and hypertension, which is associated with increased risk of cardiovascular disease (CVD) and type 2 diabetes (T2DM). Interactions between genetic and environmental factors such as diet and lifestyle, particularly over-nutrition and sedentary behavior, promote the progression and pathogenesis of these polygenic diet-related diseases. Their current prevalence is increasing dramatically to epidemic proportions. Nutrition is probably the most important environmental factor that modulates expression of genes involved in metabolic pathways and the variety of phenotypes associated with obesity, the MetS and T2DM. Furthermore, the health effects of nutrients may be modulated by genetic variants. Nutrigenomics and nutrigenetics require an understanding of nutrition, genetics, biochemistry and a range of "omic" technologies to investigate the complex interaction between genetic and environmental factors relevant to metabolic health and disease. These rapidly developing fields of nutritional science hold much promise in improving nutrition for optimal personal and public health. This review presents the current state of the art in nutrigenetic research illustrating the significance of gene-nutrient interactions in the context of metabolic disease.

Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease

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Manish M. Sood

2018-05-01

Full Text Available Introduction: Metabolomics offers considerable promise in early disease detection. We set out to test the hypothesis that routine newborn metabolic profiles at birth, obtained through screening for inborn errors of metabolism, would be associated with kidney disease and add incremental information to known clinical risk factors. Methods: We conducted a population-level cohort study in Ontario, Canada, using metabolic profiles from 1,288,905 newborns from 2006 to 2015. The primary outcome was chronic kidney disease (CKD or dialysis. Individual metabolites and their ratio combinations were examined by logistic regression after adjustment for established risk factors for kidney disease and incremental risk prediction measured. Results: CKD occurred in 2086 (0.16%, median time 612 days and dialysis in 641 (0.05%, median time 99 days infants and children. Individual metabolites consisted of amino acids, acylcarnitines, markers of fatty acid oxidation, and others. Base models incorporating clinical risk factors only provided c-statistics of 0.61 for CKD and 0.70 for dialysis. The addition of identified metabolites to risk prediciton models resulted in significant incremental improvement in the performance of both models (CKD model: c-statistic 0.66 NRI 0.36 IDI 0.04, dialysis model: c-statistic 0.77 NRI 0.57 IDI 0.09. This was consistent after internal validation using bootstrapping and a sensitivity analysis excluding outcomes within the first 30 days. Conclusion: Routinely collected screening metabolites at birth are associated with CKD and the need for dialytic therapies in infants and children, and add incremental information to traditional clinical risk factors. Keywords: chronic kidney disease, dialysis, end-stage kidney disease, metabolomics, newborn screening, pediatric, renal failure

The Role of Dietary Inflammatory Index in Cardiovascular Disease, Metabolic Syndrome and Mortality

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Miguel Ruiz-Canela

2016-08-01

Full Text Available Inflammation is an underlying pathophysiological process in chronic diseases, such as obesity, type 2 diabetes mellitus and cardiovascular disease. In fact, a number of systematic reviews have shown the association between inflammatory biomarkers, such as CRP, IL-1β, IL-6, TNF-α, IL-4, or IL-10, and cardio-metabolic diseases. Diet is one of the main lifestyle-related factors which modulates the inflammatory process. Different individual foods and dietary patterns can have a beneficial health effect associated with their anti-inflammatory properties. The dietary inflammatory index (DII was recently developed to estimate the inflammatory potential of overall diet. The aim of this review is to examine the findings of recent papers that have investigated the association between the DII, cardio-metabolic risk factors and cardiovascular disease. The relevance of the DII score in the association between inflammation and cardio-metabolic diseases is critically appraised, as well as its role in the context of healthy dietary patterns. We conclude that the DII score seems to be a useful tool to appraise the inflammatory capacity of the diet and to better understand the relationships between diet, inflammation, and cardio-metabolic diseases.

Chronic obstructive pulmonary disease candidate gene prioritization based on metabolic networks and functional information.

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Xinyan Wang

Full Text Available Chronic obstructive pulmonary disease (COPD is a multi-factor disease, in which metabolic disturbances played important roles. In this paper, functional information was integrated into a COPD-related metabolic network to assess similarity between genes. Then a gene prioritization method was applied to the COPD-related metabolic network to prioritize COPD candidate genes. The gene prioritization method was superior to ToppGene and ToppNet in both literature validation and functional enrichment analysis. Top-ranked genes prioritized from the metabolic perspective with functional information could promote the better understanding about the molecular mechanism of this disease. Top 100 genes might be potential markers for diagnostic and effective therapies.

Development of a metabolic biosignature for detection of early Lyme disease.

Science.gov (United States)

Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Hess, Ann M; Delorey, Mark J; Mahapatra, Sebabrata; Schriefer, Martin E; Belisle, John T

2015-06-15

Early Lyme disease patients often present to the clinic prior to developing a detectable antibody response to Borrelia burgdorferi, the etiologic agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%-40%) for early infection. The lack of an accurate laboratory test for early Lyme disease contributes to misconceptions about diagnosis and treatment, and underscores the need for new diagnostic approaches. Retrospective serum samples from patients with early Lyme disease, other diseases, and healthy controls were analyzed for small molecule metabolites by liquid chromatography-mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a biosignature for classifying early Lyme disease and non-Lyme disease patients. A statistical model of the biosignature was trained using the patients' LC-MS data, and subsequently applied as an experimental diagnostic tool with LC-MS data from additional patient sera. The accuracy of this method was compared with standard 2-tier serology. Metabolic biosignature development selected 95 molecular features that distinguished early Lyme disease patients from healthy controls. Statistical modeling reduced the biosignature to 44 molecular features, and correctly classified early Lyme disease patients and healthy controls with a sensitivity of 88% (84%-95%), and a specificity of 95% (90%-100%). Importantly, the metabolic biosignature correctly classified 77%-95% of the of serology negative Lyme disease patients. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

Energy Technology Data Exchange (ETDEWEB)

Schulz, W.; Schmidt, M.

1986-12-01

Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early.

Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

International Nuclear Information System (INIS)

Schulz, W.; Schmidt, M.; Klinikum Bamberg

1986-01-01

Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early. (orig.) [de

Circadian rhythms and metabolic syndrome: from experimental genetics to human disease.

Science.gov (United States)

Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

2010-02-19

The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal clock system, and sleep, constitute risk factors for disorders including obesity, diabetes mellitus, cardiovascular disease, thrombosis and even inflammation. An exciting aspect of the field has been the integration of behavioral and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics.

Fat and carbohydrate metabolism during exercise in late-onset Pompe disease

DEFF Research Database (Denmark)

Preisler, Nicolai; Laforet, Pascal; Madsen, Karen Lindhardt

2012-01-01

forearm exercise testing, and peak work capacity was determined. Fat and carbohydrate metabolism during cycle exercise was examined with a combination of indirect calorimetry and stable isotope methodology. Finally, the effects of an IV glucose infusion on heart rate, ratings of perceived exertion...... examined the metabolic response to exercise in patients with late-onset Pompe disease, in order to determine if a defect in energy metabolism may play a role in the pathogenesis of Pompe disease. We studied six adult patients with Pompe disease and 10 healthy subjects. The participants underwent ischemic......, and work capacity during exercise were determined. We found that peak oxidative capacity was reduced in the patients to 17.6 vs. 38.8 ml kg(-1) min(-1) in healthy subjects (p = 0.002). There were no differences in the rate of appearance and rate of oxidation of palmitate, or total fat and carbohydrate...

Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease.

Science.gov (United States)

Bear, R.; Goldstein, M.; Phillipson, E.; Ho, M.; Hammeke, M.; Feldman, R.; Handelsman, S.; Halperin, M.

1977-01-01

Eleven instances of a mixed acid-base disorder consisting of chronic respiratory acidosis and metabolic alkalosis were recognized in eight patients with chronic obstructive lung disease and carbon dioxide retention. Correction of the metabolic alkalosis led to substantial improvement in blood gas values and clinical symptoms. Patients with mixed chronic respiratory acidosis and metabolic alkalosis constitute a common subgroup of patients with chronic obstructive lung disease and carbon dioxide retention; these patients benefit from correction of the metabolic alkalosis. PMID:21028

FGF21 as a hepatokine, adipokine, and myokine in metabolism and diseases

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Nobuyuki eItoh

2014-07-01

Full Text Available Fibroblast growth factor (FGF family members are mostly secreted as signaling proteins with diverse functions in development and metabolism. FGF21 is a unique FGF with metabolic, but not proliferative activities. FGF21 is mostly induced by different kinds of stress and acts though FGF receptor 1c with β−Klotho as a cofactor in an endocrine or, in parts, autocirne/paracrine manner. Hepatic FGF21 directly acts on white adipocytes to inhibit lipolysis and acts through the brain to increase systemic glucocorticoid levels and suppress physical activity in response to starvation. It also protects against dioxin toxicity. Adipocytic FGF21 induces the browning of white adipose tissue (WAT and activates brown adipocytes in response to cold exposure. It also acts as an upstream effector of adiponectin in white adipocytes. Myocytic FGF21 protects against diet-induced obesity and insulin resistance, induces the browning of WAT, and protects against cardiac hypertrophy. In addition, Fgf21 polymorphisms are possibly related with metabolic diseases and FGF21 are biomarker of metabolic diseases. These findings indicate that FGF21 plays roles as a hepatokine, adipokine, and myokine in metabolism, injury protection, and diseases.

Therapeutic potential of Mediator complex subunits in metabolic diseases.

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Ranjan, Amol; Ansari, Suraiya A

2018-01-01

The multisubunit Mediator is an evolutionary conserved transcriptional coregulatory complex in eukaryotes. It is needed for the transcriptional regulation of gene expression in general as well as in a gene specific manner. Mediator complex subunits interact with different transcription factors as well as components of RNA Pol II transcription initiation complex and in doing so act as a bridge between gene specific transcription factors and general Pol II transcription machinery. Specific interaction of various Mediator subunits with nuclear receptors (NRs) and other transcription factors involved in metabolism has been reported in different studies. Evidences indicate that ligand-activated NRs recruit Mediator complex for RNA Pol II-dependent gene transcription. These NRs have been explored as therapeutic targets in different metabolic diseases; however, they show side-effects as targets due to their overlapping involvement in different signaling pathways. Here we discuss the interaction of various Mediator subunits with transcription factors involved in metabolism and whether specific interaction of these transcription factors with Mediator subunits could be potentially utilized as therapeutic strategy in a variety of metabolic diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease

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S A Butrova

2008-06-01

Full Text Available The mechanism of action of metformin is realized through activation of cAMP-dependent protein kinase, leading to a decrease hepatic glucose production as well as to decrease the synthesis of triglycerides and an increase in fat oxidation. Several studies have demonstrated the positive effect of the drug in non-alcoholic fatty liver disease, manifested in reducing the activity of enzymes, reducing the size of the liver and insulin resistance. The aim of our study was to evaluate the effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease. The study found that the use Siofor 850 mg 2 times a day in conjunction with a reduced-calorie nutrition in patients with metabolic syndrome and nonalcoholic fatty liver disease leads to a significant reduction in insulin resistance associated with decreased activity of transaminases, improvement of metabolic parameters. The therapy Siofor majority of patients (60% with metabolic syndrome and nonalcoholic fatty liver disease achieved a clinically significant weight loss and improved body composition. Application Siofor improves lifestyle changes in obese patients with non-alcoholic liver disease dirovoy and metabolic disorders.

Lipidomics: Novel insight into the biochemical mechanism of lipid metabolism and dysregulation-associated disease.

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Zhao, Ying-Yong; Miao, Hua; Cheng, Xian-Long; Wei, Feng

2015-10-05

The application of lipidomics, after genomics, proteomics and metabolomics, offered largely opportunities to illuminate the entire spectrum of lipidome based on a quantitative or semi-quantitative level in a biological system. When combined with advances in proteomics and metabolomics high-throughput platforms, lipidomics provided the opportunity for analyzing the unique roles of specific lipids in complex cellular processes. Abnormal lipid metabolism was demonstrated to be greatly implicated in many human lifestyle-related diseases. In this review, we focused on lipidomic applications in brain injury disease, cancer, metabolic disease, cardiovascular disease, respiratory disease and infectious disease to discover disease biomarkers and illustrate biochemical metabolic pathways. We also discussed the analytical techniques, future perspectives and potential problems of lipidomic applications. The application of lipidomics in disease biomarker discovery provides the opportunity for gaining novel insights into biochemical mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Adiponectin in patients with metabolic syndrome and diseases of the liver, bile ducts and pancreas].

Science.gov (United States)

Vašura, Adam; Blaho, Martin; Dítě, Petr; Kupka, Tomáš; Svoboda, Pavel; Martínek, Arnošt

Epidemiological data show that the metabolic syndrome can be diagnosed in up to 30 % of the population. Regarding 5 components of the metabolic syndrome, three of them, in case of positivity (visceral obesity, arterial hypertension, hypertriglyceridemia, changes of HDL-cholesterol levels and type 2 diabetes mellitus), are pathogenic factors which are the most frequently related to cardiovascular diseases, but currently they are also the focus of interest for gastroenterologists. The relationship between non-alcoholic hepatic steatosis, including non-alcoholic steatohepatitis, has been described. Less is known so far about the relation to the pancreas disease, particularly with respect to the status referred to as non-alcoholic fatty pancreas disease. The hormone selectively produced by adipose tissue is adiponectin. This protein is studied as a possible biomarker in people with metabolic syndrome, including obesity. Besides that, there is a question studied whether adiponectin can also play a significant role in the pathogenesis of diseases associated with fat building up in parenchymatous organs. Finding a reliable biomarker for patients with metabolic syndrome or diseases of the liver, biliary system and pancreas in relation to metabolic syndrome, presents a big challenge. And adiponectin is one of the promising biomarkers.Key words: adiponectin - biliary disease - metabolic syndrome - pancreatic steatosis - steatohepatitis.

Impact of Weight Regain on Metabolic Disease Risk: A Review of Human Trials

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Cynthia M. Kroeger

2014-01-01

Full Text Available Dietary restriction interventions are effective for weight loss and reduction of chronic disease risk. Unfortunately, most people tend to regain much of this lost weight within one year after intervention. While some studies suggest that minor degrees of weight regain have no effect on metabolic disease risk parameters, other studies demonstrate a complete reversal in metabolic benefits. In light of these conflicting findings, it is of interest to determine how complete weight maintenance versus mild weight regain affects key risk parameters. These findings would have important clinical implications, as they could help identify a weight regain threshold that could preserve the metabolic benefits of weight loss. Accordingly, this review examined the impact of no weight regain versus mild regain on various metabolic disease risk parameters, including plasma lipids, blood pressure, glucose, and insulin concentrations, in adult subjects.

Perfusion and metabolism imaging studies in Parkinson's disease

DEFF Research Database (Denmark)

Borghammer, Per

2012-01-01

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are important tools in the evaluation of brain blood flow and glucose metabolism in Parkinson's disease (PD). However, conflicting results are reported in the literature depending on the type of imaging data...

Glutathione Metabolism and Parkinson’s Disease

OpenAIRE

Smeyne, Michelle; Smeyne, Richard Jay

2013-01-01

It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson’s disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how...

Manipulating the Circadian and Sleep Cycles to Protect Against Metabolic Disease

OpenAIRE

Nohara, Kazunari; Yoo, Seung-Hee; Chen, Zheng (Jake)

2015-01-01

Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that reg...

A prospective study of monitoring practices for metabolic disease in antipsychotic-treated community psychiatric patients

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Watkinson Helen MO

2007-06-01

Full Text Available Abstract Background Patients with severe mental illness are at increased risk for metabolic and cardiovascular disease. A number of recent guidelines and consensus statements recommend stringent monitoring of metabolic function in individuals receiving antipsychotic drugs. Methods We conducted a prospective cohort study of 106 community-treated psychiatric patients from across the diagnostic spectrum from the Northeast of England to investigate changes in metabolic status and monitoring practices for metabolic and cardiovascular disease. We undertook detailed anthropometric and metabolic assessment at baseline and follow-up, and examined clinical notes and hospital laboratory records to ascertain monitoring practices. Results A high prevalence of undiagnosed and untreated metabolic disease was present at baseline assessment. Mean follow-up time was 599.3 (SD ± 235.4 days. Body mass index (p 50% of subjects had neither blood glucose nor lipids monitored during the follow-up period. Conclusion This cohort has a high prevalence of metabolic disease and heightened cardiovascular risk. Despite the publication of a number of recommendations regarding physical health screening in this population, monitoring rates are poor, and physical health worsened during the follow-up period.

The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

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Hutcheson, Rebecca; Rocic, Petra

2012-01-01

The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD) in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs), and angiotensin II converting enzyme (ACE) inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome. PMID:22829804

The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

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Rebecca Hutcheson

2012-01-01

Full Text Available The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs, and angiotensin II converting enzyme (ACE inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome.

Microvesicles/exosomes as potential novel biomarkers of metabolic diseases

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Müller G

2012-08-01

Full Text Available Günter MüllerDepartment of Biology 1, Genetics, Ludwig-Maximilians University Munich, Biocenter, Munich, GermanyAbstract: Biomarkers are of tremendous importance for the prediction, diagnosis, and observation of the therapeutic success of common complex multifactorial metabolic diseases, such as type II diabetes and obesity. However, the predictive power of the traditional biomarkers used (eg, plasma metabolites and cytokines, body parameters is apparently not sufficient for reliable monitoring of stage-dependent pathogenesis starting with the healthy state via its initiation and development to the established disease and further progression to late clinical outcomes. Moreover, the elucidation of putative considerable differences in the underlying pathogenetic pathways (eg, related to cellular/tissue origin, epigenetic and environmental effects within the patient population and, consequently, the differentiation between individual options for disease prevention and therapy – hallmarks of personalized medicine – plays only a minor role in the traditional biomarker concept of metabolic diseases. In contrast, multidimensional and interdependent patterns of genetic, epigenetic, and phenotypic markers presumably will add a novel quality to predictive values, provided they can be followed routinely along the complete individual disease pathway with sufficient precision. These requirements may be fulfilled by small membrane vesicles, which are so-called exosomes and microvesicles (EMVs that are released via two distinct molecular mechanisms from a wide variety of tissue and blood cells into the circulation in response to normal and stress/pathogenic conditions and are equipped with a multitude of transmembrane, soluble and glycosylphosphatidylinositol-anchored proteins, mRNAs, and microRNAs. Based on the currently available data, EMVs seem to reflect the diverse functional and dysfunctional states of the releasing cells and tissues along the

Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications.

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Regenboog, Martine; van Kuilenburg, André B P; Verheij, Joanne; Swinkels, Dorine W; Hollak, Carla E M

2016-11-01

Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mitochondrial metabolism in early neural fate and its relevance for neuronal disease modeling.

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Lorenz, Carmen; Prigione, Alessandro

2017-12-01

Modulation of energy metabolism is emerging as a key aspect associated with cell fate transition. The establishment of a correct metabolic program is particularly relevant for neural cells given their high bioenergetic requirements. Accordingly, diseases of the nervous system commonly involve mitochondrial impairment. Recent studies in animals and in neural derivatives of human pluripotent stem cells (PSCs) highlighted the importance of mitochondrial metabolism for neural fate decisions in health and disease. The mitochondria-based metabolic program of early neurogenesis suggests that PSC-derived neural stem cells (NSCs) may be used for modeling neurological disorders. Understanding how metabolic programming is orchestrated during neural commitment may provide important information for the development of therapies against conditions affecting neural functions, including aging and mitochondrial disorders. Copyright © 2017. Published by Elsevier Ltd.

Lipotoxicity in macrophages: evidence from diseases associated with the metabolic syndrome.

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Prieur, Xavier; Roszer, Tamás; Ricote, Mercedes

2010-03-01

Accumulation of lipid metabolites within non-adipose tissues can induce chronic inflammation by promoting macrophage infiltration and activation. Oxidized and glycated lipoproteins, free fatty acids, free cholesterol, triacylglycerols, diacylglycerols and ceramides have long been known to induce cellular dysfunction through their pro-inflammatory and pro-apoptotic properties. Emerging evidence suggests that macrophage activation by lipid metabolites and further modulation by lipid signaling represents a common pathogenic mechanism underlying lipotoxicity in atherosclerosis, obesity-associated insulin resistance and inflammatory diseases related to metabolic syndrome such as liver steatosis and chronic kidney disease. In this review, we discuss the latest discoveries that support the role of lipids in modulating the macrophage phenotype in different metabolic diseases. We describe the common mechanisms by which lipid derivatives, through modulation of macrophage function, promote plaque instability in the arterial wall, impair insulin responsiveness and contribute to inflammatory liver, muscle and kidney disease. We discuss the molecular mechanism of lipid activation of pro-inflammatory pathways (JNK, NFkappaB) and the key roles played by the PPAR and LXR nuclear receptors-lipid sensors that link lipid metabolism and inflammation. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Hampered Vitamin B12 Metabolism in Gaucher Disease?

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Luciana Hannibal PhD

2017-02-01

Full Text Available Untreated vitamin B 12 deficiency manifests clinically with hematological abnormalities and combined degeneration of the spinal cord and polyneuropathy and biochemically with elevated homocysteine (Hcy and methylmalonic acid (MMA. Vitamin B 12 metabolism involves various cellular compartments including the lysosome, and a disruption in the lysosomal and endocytic pathways induces functional deficiency of this micronutrient. Gaucher disease (GD is characterized by dysfunctional lysosomal metabolism brought about by mutations in the enzyme beta-glucocerebrosidase (Online Mendelian Inheritance in Man (OMIM: 606463; Enzyme Commission (EC 3.2.1.45, gene: GBA1 . In this study, we collected and examined available literature on the associations between GD, the second most prevalent lysosomal storage disorder in humans, and hampered vitamin B 12 metabolism. Results from independent cohorts of patients show elevated circulating holotranscobalamin without changes in vitamin B 12 levels in serum. Gaucher disease patients under enzyme replacement therapy present normal levels of Hcy and MMA. Although within the normal range, a significant increase in Hcy and MMA with normal serum vitamin B 12 was documented in treated GD patients with polyneuropathy versus treated GD patients without polyneuropathy. Thus, a functional deficiency of vitamin B 12 caused by disrupted lysosomal metabolism in GD is a plausible mechanism, contributing to the neurological form of the disorder but this awaits confirmation. Observational studies suggest that an assessment of vitamin B 12 status prior to the initiation of enzyme replacement therapy may shed light on the role of vitamin B 12 in the pathogenesis and progression of GD.

Black leaf streak disease affects starch metabolism in banana fruit.

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Saraiva, Lorenzo de Amorim; Castelan, Florence Polegato; Shitakubo, Renata; Hassimotto, Neuza Mariko Aymoto; Purgatto, Eduardo; Chillet, Marc; Cordenunsi, Beatriz Rosana

2013-06-12

Black leaf streak disease (BLSD), also known as black sigatoka, represents the main foliar disease in Brazilian banana plantations. In addition to photosynthetic leaf area losses and yield losses, this disease causes an alteration in the pre- and postharvest behavior of the fruit. The aim of this work was to investigate the starch metabolism of fruits during fruit ripening from plants infected with BLSD by evaluating carbohydrate content (i.e., starch, soluble sugars, oligosaccharides, amylose), phenolic compound content, phytohormones, enzymatic activities (i.e., starch phosphorylases, α- and β-amylase), and starch granules. The results indicated that the starch metabolism in banana fruit ripening is affected by BLSD infection. Fruit from infested plots contained unusual amounts of soluble sugars in the green stage and smaller starch granules and showed a different pattern of superficial degradation. Enzymatic activities linked to starch degradation were also altered by the disease. Moreover, the levels of indole-acetic acid and phenolic compounds indicated an advanced fruit physiological age for fruits from infested plots.

Molecular Paths Linking Metabolic Diseases, Gut Microbiota Dysbiosis and Enterobacteria Infections.

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Serino, Matteo

2018-03-02

Alterations of both ecology and functions of gut microbiota are conspicuous traits of several inflammatory pathologies, notably metabolic diseases such as obesity and type 2 diabetes. Moreover, the proliferation of enterobacteria, subdominant members of the intestinal microbial ecosystem, has been shown to be favored by Western diet, the strongest inducer of both metabolic diseases and gut microbiota dysbiosis. The inner interdependence between the host and the gut microbiota is based on a plethora of molecular mechanisms by which host and intestinal microbes modify each other. Among these mechanisms are as follows: (i) the well-known metabolic impact of short chain fatty acids, produced by microbial fermentation of complex carbohydrates from plants; (ii) a mutual modulation of miRNAs expression, both on the eukaryotic (host) and prokaryotic (gut microbes) side; (iii) the production by enterobacteria of virulence factors such as the genotoxin colibactin, shown to alter the integrity of host genome and induce a senescence-like phenotype in vitro; (iv) the microbial excretion of outer-membrane vesicles, which, in addition to other functions, may act as a carrier for multiple molecules such as toxins to be delivered to target cells. In this review, I describe the major molecular mechanisms by which gut microbes exert their metabolic impact at a multi-organ level (the gut barrier being in the front line) and support the emerging triad of metabolic diseases, gut microbiota dysbiosis and enterobacteria infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases.

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Scholz, Gerhard H; Hanefeld, Markolf

2016-10-01

Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

Interlinkage among cardio-metabolic disease markers in an urban poor setting in Nairobi, Kenya

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Tilahun Nigatu Haregu

2016-02-01

Full Text Available Introduction: The main cardio-metabolic diseases – mostly cardiovascular diseases such as stroke and ischemic heart disease – share common clinical markers such as raised blood pressure and blood glucose. The pathways of development of many of these conditions are also interlinked. In this regard, a higher level of co-occurrence of the main cardio-metabolic disease markers is expected. Evidence about the patterns of occurrence of cardio-metabolic markers and their interlinkage in the sub-Saharan African setting is inadequate. Objective: The goal of the study was to describe the interlinkage among common cardio-metabolic disease markers in an African setting. Design: We used data collected in a cross-sectional study from 5,190 study participants as part of cardiovascular disease risk assessment in the urban slums of Nairobi, Kenya. Five commonly used clinical markers of cardio-metabolic conditions were considered in this analysis. These markers were waist circumference, blood pressure, random blood glucose, total blood cholesterol, and triglyceride levels. Patterns of these markers were described using means, standard deviations, and proportions. The associations between the markers were determined using odds ratios. Results: The weighted prevalence of central obesity, hypertension, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were 12.3%, 7.0%, 2.5%, 10.3%, and 17.3%, respectively. Women had a higher prevalence of central obesity and hypercholesterolemia as compared to men. Blood glucose was strongly associated with central obesity, blood pressure, and triglyceride levels, whereas the association between blood glucose and total blood cholesterol was not statistically significant. Conclusions: This study shows that most of the common cardio-metabolic markers are interlinked, suggesting a higher probability of comorbidity due to cardio-metabolic conditions and thus the need for integrated approaches.

Oxidative Stress and Metabolic Syndrome: Cause or Consequence of Alzheimer's Disease?

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Diana Luque-Contreras

2014-01-01

Full Text Available Alzheimer’s disease (AD is a major neurodegenerative disease affecting the elderly. Clinically, it is characterized by a progressive loss of memory and cognitive function. Neuropathologically, it is characterized by the presence of extracellular β-amyloid (Aβ deposited as neuritic plaques (NP and neurofibrillary tangles (NFT made of abnormal and hyperphosphorylated tau protein. These lesions are capable of generating the neuronal damage that leads to cell death and cognitive failure through the generation of reactive oxygen species (ROS. Evidence indicates the critical role of Aβ metabolism in prompting the oxidative stress observed in AD patients. However, it has also been proposed that oxidative damage precedes the onset of clinical and pathological AD symptoms, including amyloid-β deposition, neurofibrillary tangle formation, vascular malfunction, metabolic syndrome, and cognitive decline. This paper provides a brief description of the three main proteins associated with the development of the disease (Aβ, tau, and ApoE and describes their role in the generation of oxidative stress. Finally, we describe the mitochondrial alterations that are generated by Aβ and examine the relationship of vascular damage which is a potential prognostic tool of metabolic syndrome. In addition, new therapeutic approaches targeting ROS sources and metabolic support were reported.

Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease.

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Smith, Gina A; Fearnley, Gareth W; Harrison, Michael A; Tomlinson, Darren C; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

2015-07-01

Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival. The family of VEGF isoforms regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is implicated in major chronic disease states including atherosclerosis, diabetes, and cancer. More recent studies implicate a strong link between response to VEGF and regulation of vascular metabolism. Understanding how this family of multitasking cytokines regulates cell and animal function has implications for treating many different diseases.

[Rehabilitation for digestive and metabolic diseases. Quo vadis?].

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Stockbrugger, R; Rosemeyer, D; Armbrecht, U

2010-10-01

The position of rehabilitation in gastroenterology, hepatology and metabolic diseases has changed little in the last 25 years. Initial improvements in quality are oriented more to the content of rehabilitative measures and less to organizational basic conditions. Nevertheless, there is an urgent need for action if rehabilitation medicine is to achieve an equivalent and recognized position in the interaction between primary care and other medical specialties. In this article suggestions for expedient prerequisites and utilization options of rehabilitation in the fields of hepatogastroenterology and metabolism will be presented, which are also oriented to the exemplary implemented concepts from Sweden and The Netherlands.

Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

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Matsuda, Hiroshi

2001-01-01

In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOEε4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the ε4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single ε4 allele. On the contrary the relation of ε4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection or statistical parametric mapping

Metabolic syndrome and risk factors for non-alcoholic fatty liver disease

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Mônica Rodrigues de Araújo Souza

2012-03-01

Full Text Available CONTEXT: Non-alcoholic fatty liver disease (NAFLD, hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS to non-alcoholic steatohepatitis (NASH. The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1 recognize patients with metabolic syndrome at high risk for NAFLD, 2 elucidate pathways common to other co-morbidities, 3

Progranulin: at the interface of neurodegenerative and metabolic diseases.

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Nguyen, Andrew D; Nguyen, Thi A; Martens, Lauren Herl; Mitic, Laura L; Farese, Robert V

2013-12-01

Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor-like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic function. We review here progranulin biology in both neurodegenerative and metabolic diseases. In particular, we highlight the growth factor-like, trophic, and anti-inflammatory properties of progranulin as potential unifying themes in these seemingly divergent conditions. We also discuss potential therapeutic options for raising progranulin levels to treat progranulin-deficient FTD, as well as the possible consequences of such treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia

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Sasaki, Masayuki; Ichiya, Yuichi; Hosokawa, Shinichi; Otsuka, Makoto; Kuwabara, Yasuo; Fukumura, Toshimitsu; Kato, Motohiro; Goto, Ikuo; Masuda, Kouji [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1992-11-01

By means of positron emission tomography, the cerebral glucose metabolism in 5 patients with Parkinson's disease with dementia was compared with that in 9 patients without dementia, and that in 5 normal volunteers. The metabolic rates for glucose were measured by placing one hundred regions of interest. In the demented patients, cerebral glucose metabolism was diffusely decreased compared with that of the non-demented patients and the normal controls. The most significant decrease in glucose metabolism was observed in the angular gyrus (49.7% of the normal controls). The glucose metabolism in the cingulate, pre- and postcentral, occipital and subcortical regions was relatively spared (62.1 to 85.5% of the normal controls). In the patients without dementia, the glucose metabolism in each region was not significantly different from that in the normal controls. These results suggest that diffuse glucose hypometabolism in the cerebral cortex may correlate with that of patients with Parkinson's disease with dementia. (author).

Obesity and Metabolic Comorbidities: Environmental Diseases?

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Carla Lubrano

2013-01-01

Full Text Available Obesity and metabolic comorbidities represent increasing health problems. Endocrine disrupting compounds (EDCs are exogenous agents that change endocrine function and cause adverse health effects. Most EDCs are synthetic chemicals; some are natural food components as phytoestrogens. People are exposed to complex mixtures of chemicals throughout their lives. EDCs impact hormone-dependent metabolic systems and brain function. Laboratory and human studies provide compelling evidence that human chemical contamination can play a role in obesity epidemic. Chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes. EDCs can alter methylation patterns and normal epigenetic programming in cells. Oxidative stress may be induced by many of these chemicals, and accumulating evidence indicates that it plays important roles in the etiology of chronic diseases. The individual sensitivity to chemicals is variable, depending on environment and ability to metabolize hazardous chemicals. A number of genes, especially those representing antioxidant and detoxification pathways, have potential application as biomarkers of risk assessment. The potential health effects of combined exposures make the risk assessment process more complex compared to the assessment of single chemicals. Techniques and methods need to be further developed to fill data gaps and increase the knowledge on harmful exposure combinations.

Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

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Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier [Clinica Universidad de Navarra, Nuclear Medicine Department, Pamplona (Spain); Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de [Clinica Universidad de Navarra, Neurology Department, Pamplona (Spain)

2015-09-15

Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

International Nuclear Information System (INIS)

Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier; Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de

2015-01-01

Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

Association of metabolic syndrome and change in Unified Parkinson's Disease Rating Scale scores.

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Leehey, Maureen; Luo, Sheng; Sharma, Saloni; Wills, Anne-Marie A; Bainbridge, Jacquelyn L; Wong, Pei Shieen; Simon, David K; Schneider, Jay; Zhang, Yunxi; Pérez, Adriana; Dhall, Rohit; Christine, Chadwick W; Singer, Carlos; Cambi, Franca; Boyd, James T

2017-10-24

To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS ( p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS ( p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores. Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. NCT00449865. © 2017 American Academy of Neurology.

The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease.

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van der Veen, Jelske N; Kennelly, John P; Wan, Sereana; Vance, Jean E; Vance, Dennis E; Jacobs, René L

2017-09-01

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the most abundant phospholipids in all mammalian cell membranes. In the 1950s, Eugene Kennedy and co-workers performed groundbreaking research that established the general outline of many of the pathways of phospholipid biosynthesis. In recent years, the importance of phospholipid metabolism in regulating lipid, lipoprotein and whole-body energy metabolism has been demonstrated in numerous dietary studies and knockout animal models. The purpose of this review is to highlight the unappreciated impact of phospholipid metabolism on health and disease. Abnormally high, and abnormally low, cellular PC/PE molar ratios in various tissues can influence energy metabolism and have been linked to disease progression. For example, inhibition of hepatic PC synthesis impairs very low density lipoprotein secretion and changes in hepatic phospholipid composition have been linked to fatty liver disease and impaired liver regeneration after surgery. The relative abundance of PC and PE regulates the size and dynamics of lipid droplets. In mitochondria, changes in the PC/PE molar ratio affect energy production. We highlight data showing that changes in the PC and/or PE content of various tissues are implicated in metabolic disorders such as atherosclerosis, insulin resistance and obesity. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

Fatty Liver Index and Lipid Accumulation Product Can Predict Metabolic Syndrome in Subjects without Fatty Liver Disease

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Yuan-Lung Cheng

2017-01-01

Full Text Available Background. Fatty liver index (FLI and lipid accumulation product (LAP are indexes originally designed to assess the risk of fatty liver and cardiovascular disease, respectively. Both indexes have been proven to be reliable markers of subsequent metabolic syndrome; however, their ability to predict metabolic syndrome in subjects without fatty liver disease has not been clarified. Methods. We enrolled consecutive subjects who received health check-up services at Taipei Veterans General Hospital from 2002 to 2009. Fatty liver disease was diagnosed by abdominal ultrasonography. The ability of the FLI and LAP to predict metabolic syndrome was assessed by analyzing the area under the receiver operating characteristic (AUROC curve. Results. Male sex was strongly associated with metabolic syndrome, and the LAP and FLI were better than other variables to predict metabolic syndrome among the 29,797 subjects. Both indexes were also better than other variables to detect metabolic syndrome in subjects without fatty liver disease (AUROC: 0.871 and 0.879, resp., and the predictive power was greater among women. Conclusion. Metabolic syndrome increases the cardiovascular disease risk. The FLI and LAP could be used to recognize the syndrome in both subjects with and without fatty liver disease who require lifestyle modifications and counseling.

Perfusion and metabolism imaging studies in Parkinson's disease

DEFF Research Database (Denmark)

Borghammer, Per

2012-01-01

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are important tools in the evaluation of brain blood flow and glucose metabolism in Parkinson's disease (PD). However, conflicting results are reported in the literature depending on the type of imaging data....... It is concluded that PD most likely is characterized by widespread cortical hypometabolism, probably even at early disease stages. Widespread subcortical hypermetabolism is probably not a feature of PD, although certain small basal ganglia structures, such as the external pallidum, may display true...

[Carbohydrate metabolism in patients with acromegaly and Itsenko-Cushing disease].

Science.gov (United States)

Matchekhina, L V; Belaya, Zh E; Melnichenko, G A; Shestakova, M V

2015-01-01

The relevance of investigating carbohydrate metabolism (CM) in patients with acromegaly and Itsenko-Cushing disease is attributable to frequent glucose metabolic disturbances, on the one hand, and to difficulties in choosing sugar-lowering therapy in these categories of patients, on the other. The efficiency of hyperglycemia treatment in these patients may be reduced due to problems in achieving remission/cure of the underlying disease and to specific therapy favoring hyperglycemia. The top-priority tasks are to search for ways of reducing the frequency of CM abnormalities in patients with neuroendocrine diseases and to elaborate sugar-lowering therapy regimens. There is a growing interest in studies of the role of the incretin system in the pathogenesis of secondary hyperglycemias associated with neuroendocrine diseases. Nevertheless, few works have been published on this subject matter because of its novelty. There is a need for a further closer study of the specific features of incretin system function and the pharmacodynamics of incretin mimetics that are potential candidates as first-line drugs to treat secondary hyperglycemias. This paper attempts to summarize the available data obtained from studies into CM in neuroendocrine diseases.

Glucose metabolism in small subcortical structures in Parkinson's disease

DEFF Research Database (Denmark)

Borghammer, Per; Hansen, Søren B; Eggers, Carsten

2012-01-01

Evidence from experimental animal models of Parkinson's disease (PD) suggests a characteristic pattern of metabolic perturbation in discrete, very small basal ganglia structures. These structures are generally too small to allow valid investigation by conventional positron emission tomography (PE...

Manipulating the circadian and sleep cycles to protect against metabolic disease

Directory of Open Access Journals (Sweden)

Kazunari eNohara

2015-03-01

Full Text Available Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g. obesity involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude enhancing small molecules (CEMs identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep and metabolism will also have far-reaching implications for various chronic human diseases and aging.

Manipulating the circadian and sleep cycles to protect against metabolic disease.

Science.gov (United States)

Nohara, Kazunari; Yoo, Seung-Hee; Chen, Zheng Jake

2015-01-01

Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock, and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g., obesity) involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude-enhancing small molecules (CEMs) identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep, and metabolism will also have far-reaching implications for various chronic human diseases and aging.

Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity Score.

Science.gov (United States)

Masson, Walter; Epstein, Teo; Huerín, Melina; Lobo, Lorenzo Martín; Molinero, Graciela; Angel, Adriana; Masson, Gerardo; Millán, Diana; De Francesca, Salvador; Vitagliano, Laura; Cafferata, Alberto; Losada, Pablo

2017-09-01

The estimated cardiovascular risk determined by the different risk scores, could be heterogeneous in patients with metabolic syndrome without diabetes or vascular disease. This risk stratification could be improved by detecting subclinical carotid atheromatosis. To estimate the cardiovascular risk measured by different scores in patients with metabolic syndrome and analyze its association with the presence of carotid plaque. Non-diabetic patients with metabolic syndrome (Adult Treatment Panel III definition) without cardiovascular disease were enrolled. The Framingham score, the Reynolds score, the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome Severity Calculator were calculated. Prevalence of carotid plaque was determined by ultrasound examination. A Receiver Operating Characteristic analysis was performed. A total of 238 patients were enrolled. Most patients were stratified as "low risk" by Framingham score (64%) and Reynolds score (70.1%). Using the 2013 ACC/AHA score, 45.3% of the population had a risk ≥7.5%. A significant correlation was found between classic scores but the agreement (concordance) was moderate. The correlation between classical scores and the Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of carotid plaque was 28.2%. The continuous metabolic syndrome score used in our study showed a good predictive power to detect carotid plaque (area under the curve 0.752). In this population, the calculated cardiovascular risk was heterogenic. The prevalence of carotid plaque was high. The Metabolic Syndrome Severity Calculator showed a good predictive power to detect carotid plaque.

The effect of maternal Inflammation on foetal programming of metabolic disease

DEFF Research Database (Denmark)

Ingvorsen, Camilla; Pedersen, Susanne Brix; Ozanne, S. E.

2015-01-01

‐grade inflammatory diseases, such as rheumatoid arthritis, that pregnancy can improve disease state. If pregnancy is also capable of suppressing the obesity‐associated inflammation, the immunological markers might be less likely to affect metabolic programming in the developing foetus than otherwise implied....

Role of innate lymphoid cells in obesity and metabolic disease

Science.gov (United States)

Saetang, Jirakrit; Sangkhathat, Surasak

2018-01-01

The immune system has previously been demonstrated to be associated with the pathophysiological development of metabolic abnormalities. However, the mechanisms linking immunity to metabolic disease remain to be fully elucidated. It has previously been suggested that innate lymphoid cells (ILCs) may be involved in the progression of numerous types of metabolic diseases as these cells act as suppressors and promoters for obesity and associated conditions, and are particularly involved in adipose tissue inflammation, which is a major feature of metabolic imbalance. Group 2 ILCs (ILC2s) have been revealed as anti-obese immune regulators by secreting anti-inflammatory cytokines and promoting the polarization of M2 macrophages, whereas group 1 ILCs (ILC1s), including natural killer cells, may promote adipose tissue inflammation via production of interferon-γ, which in turn polarizes macrophages toward the M1 type. The majority of studies to date have demonstrated the pathological association between ILCs and obesity in the context of adipose tissue inflammation, whereas the roles of ILCs in other organs which participate in obesity development have not been fully characterized. Therefore, identifying the roles of all types of ILCs as central components mediating obesity-associated inflammation, is of primary concern, and may lead to the discovery of novel preventative and therapeutic interventions. PMID:29138853

Metabolic adaptations in models of fatty liver disease : Of mice and math

NARCIS (Netherlands)

Hijmans, Brenda

2017-01-01

The increasing incidence of overweight is accompanied by a plethora of medical symptoms together called the metabolic syndrome. Non-alcoholic fatty liver disease, characterized by persistent storage of lipids in the liver, is regarded as the hepatic component of the metabolic syndrome. An imbalance

Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).

Science.gov (United States)

Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Andre, Barbara G; Hess, Ann M; Delorey, Mark J; Pilgard, Mark A; Johnson, Barbara J; Webb, Kristofor; Islam, M Nurul; Pegalajar-Jurado, Adoracion; Molla, Irida; Jewett, Mollie W; Belisle, John T

2017-08-16

Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N -acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. Development of classification models with the 261-MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to inform patient management by objectively distinguishing early Lyme disease from an illness with nearly identical symptoms. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The 2009 stock conference report: inflammation, obesity and metabolic disease.

Science.gov (United States)

Hevener, A L; Febbraio, M A

2010-09-01

Obesity is linked with many deleterious health consequences and is associated with increased risk of chronic disease including type 2 diabetes, atherosclerosis and certain forms of cancer. Recent work has highlighted the impact of obesity to activate inflammatory gene networks and suggests a causal function of inflammation in the pathogenesis of the metabolic syndrome. Since 2005, when Dr Gokhan Hotamisligil chaired the fourth Stock Conference in Istanbul, Turkey, entitled 'Obesity and Inflammation', there has been an explosion of studies investigating the relationship between obesity, inflammation and substrate metabolism. The exuberance surrounding this field of research is exemplified by the body of work that has been published in these past 4 years, including over 1400 publications. During this time, several novel mechanisms relating to cellular inflammation have been uncovered including the role of the hematopoietic system, toll-like receptor activation, endoplasmic reticulum stress and very recently T-cell activation in obesity-induced insulin resistance. These discoveries have led us to rethink cellular nutrient sensing and its role in inflammation and metabolic disease. Despite burgeoning investigation in this field, there still remain a number of unanswered questions. This review that evolved from the 2009 Stock Conference summarizes current research and identifies the deficiencies in our understanding of this topic. The overall goal of this Stock Conference was to bring together leading investigators in the field of inflammation and obesity research in the hope of fostering new ideas, thus advancing the pursuit of novel therapeutic strategies to reduce disease risk and or better treat chronic disease including type 2 diabetes, cardiovascular disease and cancer. © 2009 The Authors. obesity reviews © 2009 International Association for the Study of Obesity.

[Endocrinological diseases, metabolic diseases, sexuality].

Science.gov (United States)

Lemaire, Antoine

2014-10-01

Sexuality is regularly evaluated in media surveys. Relations between sexual problems and some chronic pathologies as diabetes or metabolic syndrome have been brought to light. Androgen deficiency in the aging male has become a topic of increasing interest. Hormones play an important role in sexual function and relation between hormonal status and metabolic data are now well established. Copyright © 2014. Published by Elsevier Masson SAS.

Hematopoietic Gene Therapies for Metabolic and Neurologic Diseases.

Science.gov (United States)

Biffi, Alessandra

2017-10-01

Increasingly, patients affected by metabolic diseases affecting the central nervous system and neuroinflammatory disorders receive hematopoietic cell transplantation (HCT) in the attempt to slow the course of their disease, delay or attenuate symptoms, and improve pathologic findings. The possible replacement of brain-resident myeloid cells by the transplanted cell progeny contributes to clinical benefit. Genetic engineering of the cells to be transplanted (hematopoietic stem cell) may endow the brain myeloid progeny of these cells with enhanced or novel functions, contributing to therapeutic effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models.

Science.gov (United States)

Bakker, Barbara M; van Eunen, Karen; Jeneson, Jeroen A L; van Riel, Natal A W; Bruggeman, Frank J; Teusink, Bas

2010-10-01

Human metabolic diseases are typically network diseases. This holds not only for multifactorial diseases, such as metabolic syndrome or Type 2 diabetes, but even when a single gene defect is the primary cause, where the adaptive response of the entire network determines the severity of disease. The latter may differ between individuals carrying the same mutation. Understanding the adaptive responses of human metabolism naturally requires a systems biology approach. Modelling of metabolic pathways in micro-organisms and some mammalian tissues has yielded many insights, qualitative as well as quantitative, into their control and regulation. Yet, even for a well-known pathway such as glycolysis, precise predictions of metabolite dynamics from experimentally determined enzyme kinetics have been only moderately successful. In the present review, we compare kinetic models of glycolysis in three cell types (African trypanosomes, yeast and skeletal muscle), evaluate their predictive power and identify limitations in our understanding. Although each of these models has its own merits and shortcomings, they also share common features. For example, in each case independently measured enzyme kinetic parameters were used as input. Based on these 'lessons from glycolysis', we will discuss how to make best use of kinetic computer models to advance our understanding of human metabolic diseases.

Metabolic epidermal necrosis in two dogs with different underlying diseases.

Science.gov (United States)

Bond, R; McNeil, P E; Evans, H; Srebernik, N

1995-05-06

Two dogs with metabolic epidermal necrosis had hyperkeratosis of the footpads accompanied by erythematous, erosive and crusting lesions affecting the muzzle, external genitalia, perineum and periocular regions. Histopathological examination of skin biopsies revealed a superficial hydropic dermatitis with marked parakeratosis. Both dogs had high plasma activities of alkaline phosphatase and alanine aminotransferase and high concentrations of glucose, and also a marked hypoaminoacidaemia. Despite these similarities, the cutaneous eruptions were associated with different underlying diseases. One dog had a pancreatic carcinoma which had metastasised widely; the primary tumour and the metastases showed glucagon immunoreactivity on immunocytochemical staining, and the dog's plasma glucagon concentration was markedly greater than that of control dogs. The other dog had diffuse hepatic disease; its plasma glucagon concentration was similar to that of control samples and cirrhosis was identified post mortem. Metabolic epidermal necrosis in dogs is a distinct cutaneous reaction pattern which may be associated with different underlying systemic diseases; however, the pathogenesis of the skin lesions remains unclear.

Cyclic vomiting syndrome masking a fatal metabolic disease.

LENUS (Irish Health Repository)

Fitzgerald, Marianne

2013-05-01

Disorders of fatty acid oxidation are rare but can be fatal. Hypoglycaemia with acidosis is a cardinal feature. Cases may present during early childhood or can be delayed into adolescence or beyond. We present a case of multiple acyl-coenzyme A dehydrogenase deficiency (MADD), an extremely rare disorder of fatty acid oxidation. Our 20-year-old patient presented with cardiovascular collapse, raised anion gap metabolic acidosis and non-ketotic hypoglycaemia. She subsequently developed multi-organ failure and sadly died. She had a previous diagnosis of cyclic vomiting syndrome (CVS) for more than 10 years, warranting frequent hospital admissions. The association between CVS and MADD has been made before though the exact relationship is unclear. All patients with persistent severe CVS should have metabolic investigations to exclude disorders of fatty acid oxidation. In case of non-ketotic hypoglycaemia with acidosis, the patient should be urgently referred to a specialist in metabolic diseases. All practitioners should be aware of these rare disorders as a cause of unexplained acidosis.

Metabolomic applications to decipher gut microbial metabolic influence in health and disease

Directory of Open Access Journals (Sweden)

Francois-Pierre eMartin

2012-04-01

Full Text Available Dietary preferences and nutrients composition have been shown to influence human and gut microbial metabolism, which ultimately has specific effects on health and diseases’ risk. Increasingly, results from molecular biology and microbiology demonstrate the key role of the gut microbiota metabolic interface to the overall mammalian host’s health status. There is therefore raising interest in nutrition research to characterize the molecular foundations of the gut microbial mammalian cross-talk at both physiological and biochemical pathway levels. Tackling these challenges can be achieved through systems biology approaches, such as metabolomics, to underpin the highly complex metabolic exchanges between diverse biological compartments, including organs, systemic biofluids and microbial symbionts. By the development of specific biomarkers for prediction of health and disease, metabolomics is increasingly used in clinical applications as regard to disease aetiology, diagnostic stratification and potentially mechanism of action of therapeutical and nutraceutical solutions. Surprisingly, an increasing number of metabolomics investigations in pre-clinical and clinical studies based on proton nuclear magnetic resonance (1H NMR spectroscopy and mass spectrometry (MS provided compelling evidence that system wide and organ-specific biochemical processes are under the influence of gut microbial metabolism. This review aims at describing recent applications of metabolomics in clinical fields where main objective is to discern the biochemical mechanisms under the influence of the gut microbiota, with insight into gastrointestinal health and diseases diagnostics and improvement of homeostasis metabolic regulation.

Hexarelin Signaling to PPARγ in Metabolic Diseases

Directory of Open Access Journals (Sweden)

Amélie Rodrigue-Way

2008-01-01

Full Text Available Investigating the metabolic functions of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ has been extremely rewarding over the past years. Uncovering the biologic roles of PPARγ and its mechanism of action has greatly advanced our understanding of the transcriptional control of lipid and glucose metabolism, and compounds such as thiazolidinediones which directly regulate PPARγ have proven to exhibit potent insulin-sensitizer effects in the treatment of diabetes. We review here recent advances on the emerging role of growth hormone releasing peptides in regulating PPARγ through interaction with scavenger receptor CD36 and ghrelin GHS-R1a receptor. With the impact that these peptides exert on the metabolic pathways involved in lipid metabolism and energy homeostasis, it is hoped that the development of novel approaches in the regulation of PPAR functions will bring additional therapeutic possibilities to face problems related to metabolic diseases.

UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

Science.gov (United States)

2018-03-15

Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

Development of a Novel Targeted RNAi Delivery Technology inTherapies for Metabolic Diseases

Science.gov (United States)

2017-10-01

report Impact on other disciplines: Nothing to report Impact on technology transfer: Nothing to report Impact on society : Nothing to report 5. CHANGES...AWARD NUMBER: W81XWH-15-1-0569 TITLE: Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases PRINCIPAL...COVERED 30Sep2016 - 29Sep2017 4. TITLE AND SUBTITLE Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases 5a

Features of Mineral Metabolism and Parathyroid Glands Functioning in Chronic Renal Disease

Directory of Open Access Journals (Sweden)

L.P. Martynyuk

2012-04-01

Full Text Available The calcium phosphoric metabolism was analyzed depending on the severity of renal functioning disorders. Chronic renal disease is known to be associated with impaired mineral metabolism in terms of hypocalcaemia, hyperphosphatemia and enhanced level of Ca × P product that aggravates in chronic renal failure progression. The majority of patients with nephropathy have parathyroid hormone concentration to be different from target one recommended by NKF-K/DOQI (2003, at that secondary hyperparathyroidism prevails on pre-dialysis stage of chronic renal disease, the relative hypoparathyroidism is common among the patients received dialysis.

Cerebral Metabolic Differences Associated with Cognitive Impairment in Parkinson's Disease.

Directory of Open Access Journals (Sweden)

Yilin Tang

Full Text Available To characterize cerebral glucose metabolism associated with different cognitive states in Parkinson's disease (PD using 18F-fluorodeoxyglucose (FDG and Positron Emission Tomography (PET.Three groups of patients were recruited in this study including PD patients with dementia (PDD; n = 10, with mild cognitive impairment (PD-MCI; n = 20, and with no cognitive impairment (PD-NC; n = 30. The groups were matched for age, sex, education, disease duration, motor disability, levodopa equivalent dose and Geriatric Depression Rating Scale (GDS score. All subjects underwent a FDG-PET study. Maps of regional metabolism in the three groups were compared using statistical parametric mapping (SPM5.PD-MCI patients exhibited limited areas of hypometabolism in the frontal, temporal and parahippocampal gyrus compared with the PD-NC patients (p < 0.01. PDD patients had bilateral areas of hypometabolism in the frontal and posterior parietal-occipital lobes compared with PD-MCI patients (p < 0.01, and exhibited greater metabolic reductions in comparison with PD-NC patients (p < 0.01.Compared with PD-NC patients, hypometabolism was much higher in the PDD patients than in PD-MCI patients, mainly in the posterior cortical areas. The result might suggest an association between posterior cortical hypometabolism and more severe cognitive impairment. PD-MCI might be important for early targeted therapeutic intervention and disease modification.

Lactate metabolism in chronic liver disease

DEFF Research Database (Denmark)

Jeppesen, Johanne B; Mortensen, Christian; Bendtsen, Flemming

2013-01-01

Background. In the healthy liver there is a splanchnic net-uptake of lactate caused by gluconeogenesis. It has previously been shown that patients with acute liver failure in contrast have a splanchnic release of lactate caused by a combination of accelerated glycolysis in the splanchnic region...... and a reduction in hepatic gluconeogenesis. Aims. The aims of the present study were to investigate lactate metabolism and kinetics in patients with chronic liver disease compared with a control group with normal liver function. Methods. A total of 142 patients with chronic liver disease and 14 healthy controls...... underwent a liver vein catheterization. Blood samples from the femoral artery and the hepatic and renal veins were simultaneously collected before and after stimulation with galactose. Results. The fasting lactate levels, both in the hepatic vein and in the femoral artery, were higher in the patients than...

Diminished neuronal metabolic activity in Alzheimer's disease. Review article

NARCIS (Netherlands)

Salehi, A.; Swaab, D. F.

1999-01-01

An increasing number of studies have appeared in the literature suggesting that Alzheimer's disease (AD) is a hypometabolic brain disorder. Decreased metabolism in AD has been revealed by a variety of in vivo and postmortem methods and techniques including positron emission tomography and glucose

Detection of metabolic syndrome features among childhood cancer survivors: A target to prevent disease

Directory of Open Access Journals (Sweden)

Adriana Aparecida Siviero-Miachon

2008-08-01

Full Text Available Adriana Aparecida Siviero-Miachon1, Angela Maria Spinola-Castro1, Gil Guerra-Junior21Division of Pediatric Endocrinology, Department of Pediatrics, Federal University of Sao Paulo – UNIFESP/EPM, Brazil; 2Division of Pediatric Endocrinology, Department of Pediatrics, State University of Campinas – FCM/UNICAMP, BrazilAbstract: Along with the growing epidemic of obesity, the risk of atherosclerosis, cardiovascular disease morbidity, and mortality are increasing markedly. Several risk factors for cardiovascular disease, such as visceral obesity, glucose intolerance, arterial hypertension, and dyslipidemia commonly cluster together as a condition currently known as metabolic syndrome. Thus far, insulin resistance, and endothelial dysfunction are the primary events of the metabolic syndrome. Several groups have recommended clinical criteria for the diagnosis of metabolic syndrome in adults. Nonetheless, in what concerns children and adolescents, there are no unified definitions, and modified adult criteria have been suggested by many authors, despite major problems. Some pediatric disease states are at risk for premature cardiovascular disease, with clinical coronary events occurring very early in adult life. Survivors of specific pediatric cancer groups, particularly acute lymphocytic leukemia, central nervous system tumors, sarcomas, lymphomas, testicular cancer, and following bone marrow transplantation, may develop metabolic syndrome traits due to: hormonal deficiencies (growth hormone deficiency, thyroid dysfunction, and gonadal failure, drug or radiotherapy damage, endothelial impairment, physical inactivity, adipose tissue dysfunction, and/or drug-induced magnesium deficiency. In conclusion, some primary and secondary prevention remarks are proposed in order to reduce premature cardiovascular disease risk in this particular group of patients.Keywords: metabolic syndrome X, cardiovascular diseases, insulin resistance, obesity, growth hormone

Use of radiation and radioisotopes for investigating metabolic diseases of animals in India

Energy Technology Data Exchange (ETDEWEB)

Arora, S P [National Dairy Research Inst., Karnal (India). Div. of Dairy Cattle Nutrition and Physiology

1980-03-01

In the last decade, radioisotopes have been used to investigate certain metabolic diseases of animals and radiation is being utilized to produce parasitic vaccines to vaccinate animals. Some studies in which radioisotopes have been used to investigate certain metabolic disorders are reviewed. In experiments where radioimmunoassay technique for the estimation of hormones, has been utilized, the results reveal that the animals on low level of nutrition show greater oestrous cycle lengths or even long anoestrous periods. On the other hand, irradiation has been used as a tool to produce vaccines as well as degradation of certain dietary molecules for increased utilization. A number of studies wherein /sup 35/S and /sup 15/N isotopes have been used, reveal that sulphur supplementation is essential for optimum utilization of nitrogen in the ratio of 1:10. There are certain antimetabolites in feed ingredients which affect endocrine function. Evidence indicates that high nitrate forages disturb thyroid function when sup(131)I is used to elucidate its secretion rate. Similarly certain toxic substances such as tannins have been shown to affect protein metabolism and phosphorus utilization when sup(32)P isotope is used in such studies. The use of radioisotopes has also been helpful to investigate the cause of ''Degnala'' disease prevalent in village cattle in certain states of India. With the help of sup(75)Se it has been possible to trace the metabolic disturbances which lead to the onset of this disease. Another deficiency disease, hyperkeratosis, has been shown to be caused not only because of vitamin A deficiency, but also because of zinc deficiency. The latter helps in the mobilization of a normal quantity of vitamin A from the liver into the blood vitamin A pool. There is wide scope for use of radioisotopes to investigate other metabolic diseases prevalent in livestock in this country.

Use of radiation and radioisotopes for investigating metabolic diseases of animals in India

International Nuclear Information System (INIS)

Arora, S.P.

1980-01-01

In the last one decade, radioisotopes are being used to investigate certain metabolic diseases of animals and radiations are being utilized to produce parasitic vaccines to vaccinate animals. Some studies in which radioisotopes have been used to investigate certain metabolic disorders are reviewed. In experiments, where radioimmunoassay technique for the estimation of hormones, has been utilized, the results reveal that the animals on low plane of nutrition show greater oestrous cycle lengths or even long anoestrous periods. On the other hand, irradiation has been used as a tool to produce vaccines as well as degradation of certain dietary molecules for increased utilization. A number of studies wherein 35 S and 15 N isotopes have been used, reveal that sulphur supplementation is essential for optimum utilization of nitrogen in the ratio of 1:10. There are certain antimetabolites in feed ingredients which affect endocrine function. Evidence indicates that high nitrate forages disturb thyroid function when sup(131)I is used to elucidate its secretion rate. Similarly certain toxic substances such as tannins have been shown to affect protein metabolism and phosphorus utilization when sup(32)P isotope is used in such studies. The use of radioisotopes have also been helpful to investigate the cause of ''Degnala'' disease prevalent in village cattle in certain states of India. With the help of sup(75)Se it has been possible to trace out the metabolic disturbances which lead to the onset of this disease. Another deficiency disease, hyperkeratosis, has been shown to be caused not only because of Vitamin A deficiency, but also because of zinc deficiency. The latter helps in the mobilization of normal quantity of vitamin A from the liver into the blood vitamin A pool. There is wide scope to use radioisotopes to investigate other metabolic diseases prevalent in livestock in this country. (auth.)

Chewing betel quid and the risk of metabolic disease, cardiovascular disease, and all-cause mortality: a meta-analysis.

Science.gov (United States)

Yamada, Tomohide; Hara, Kazuo; Kadowaki, Takashi

2013-01-01

Betel nut (Areca nut) is the fruit of the Areca catechu tree. Approximately 700 million individuals regularly chew betel nut (or betel quid) worldwide and it is a known risk factor for oral cancer and esophageal cancer. We performed a meta-analysis to assess the influence of chewing betel quid on metabolic diseases, cardiovascular disease, and all-cause mortality. We searched Medline, Cochrane Library, Web of Science, and Science Direct for pertinent articles (including the references) published between 1951 and 2013. The adjusted relative risk (RR) and 95% confidence interval were calculated using the random effect model. Sex was used as an independent category for comparison. Of 580 potentially relevant studies, 17 studies from Asia (5 cohort studies and 12 case-control studies) covering 388,134 subjects (range: 94 to 97,244) were selected. Seven studies (N = 121,585) showed significant dose-response relationships between betel quid consumption and the risk of events. According to pooled analysis, the adjusted RR of betel quid chewers vs. non-chewers was 1.47 (PBetel quid chewing is associated with an increased risk of metabolic disease, cardiovascular disease, and all-cause mortality. Thus, in addition to preventing oral cancer, stopping betel quid use could be a valuable public health measure for metabolic diseases that are showing a rapid increase in South-East Asia and the Western Pacific.

NMR as a probe metabolic disorders in disease and treatment

Energy Technology Data Exchange (ETDEWEB)

Yushmanov, Victor E [Russian Academy of Sciences, Moscow (Russian Federation). Inst. of Chemical Physics

1994-12-31

The effects of malignant tumors, chemical and physical factors (toxic agents, ionizing radiation) as well as of their treatment on tissue metabolism were studied by NMR imaging. The importance of NMR is highlighted since it enables to a better understanding of molecular mechanisms of diseases and therapeutic interventions, in addition to the analysis of metabolic disorders in human beings. Combined with the studies of experimental animal pathologies, may constitute a base for new types of NMR-diagnosis in vivo 10 refs.

Circadian rhythms and metabolic syndrome: from experimental genetics to human disease

OpenAIRE

Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

2010-01-01

The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal ...

Metabolic Disturbances in Children with Chronic Liver Disease

Directory of Open Access Journals (Sweden)

A Rezaeian

2014-04-01

Full Text Available Introduction: Liver disease results in complex pathophysiologic disturbances affecting nutrient digestion, absorption, distribution, storage, and use. This article aimed to present a classification of metabolic disturbances in chronic liver disease in children?   Materials and Methods: In this review study databases including proquest, pubmedcentral, scincedirect, ovid, medlineplus were been searched with keyword words such as” chronic liver disease"  ” metabolic disorder””children” between 1999 to 2014. Finally, 8 related articles have been found.   Results: Metabolic disorder in this population could be categorized in four set: 1carbohydrates, 2proteins,3 fats and 4vitamins. 1 Carbohydrates: Children with CLD are at increased risk for fasting hypoglycemia, because the capacity for glycogen storage and gluconeogenesis is reduced as a result of abnormal hepatocyte function and loss of hepatocyte mass. 2 Proteins: The liver’s capacity for plasma protein synthesis is impaired by reduced substrate availability, impaired hepatocyte function, and increased catabolism. This results in hypoalbuminemia, leading to peripheral edema and contributing to ascites. Reduced synthesis of insulin-like growth factor (IGF-1 and its binding protein IGF-BP3 by the chronically diseased liver results in growth hormone resistance and may contribute to the poor growth observed in these children. 3 Fats: There is increased fat oxidation in children with end-stage liver disease in the fed and fasting states compared with controls, which is probably related to reduced carbohydrate availability. The increased lipolysis results in a decrease in fat stores, which may not be easily replenished in the setting of the fat malabsorption that accompanies cholestasis. Reduced bile delivery to the gut results in impaired fat emulsification, and hence digestion. The products of fat digestion are also poorly absorbed, because bile is also required for micelle formation

Abnormal metabolic brain networks in Parkinson's disease from blackboard to bedside.

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Tang, Chris C; Eidelberg, David

2010-01-01

Metabolic imaging in the rest state has provided valuable information concerning the abnormalities of regional brain function that underlie idiopathic Parkinson's disease (PD). Moreover, network modeling procedures, such as spatial covariance analysis, have further allowed for the quantification of these changes at the systems level. In recent years, we have utilized this strategy to identify and validate three discrete metabolic networks in PD associated with the motor and cognitive manifestations of the disease. In this chapter, we will review and compare the specific functional topographies underlying parkinsonian akinesia/rigidity, tremor, and cognitive disturbance. While network activity progressed over time, the rate of change for each pattern was distinctive and paralleled the development of the corresponding clinical symptoms in early-stage patients. This approach is already showing great promise in identifying individuals with prodromal manifestations of PD and in assessing the rate of progression before clinical onset. Network modulation was found to correlate with the clinical effects of dopaminergic treatment and surgical interventions, such as subthalamic nucleus (STN) deep brain stimulation (DBS) and gene therapy. Abnormal metabolic networks have also been identified for atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Using multiple disease-related networks for PD, MSA, and PSP, we have developed a novel, fully automated algorithm for accurate classification at the single-patient level, even at early disease stages. Copyright © 2010 Elsevier B.V. All rights reserved.

Identification of disease- and nutrient-related metabolic fingerprints in osteoarthritic guinea pigs

NARCIS (Netherlands)

Lamers, R.-J.A.N.; Groot, J. de; Spies-Faber, E.J.; Jellema, R.H.; Kraus, V.B.; Verzijl, N.; Koppele, J.M. te; Spijksma, G.K.; Vogels, J.T.W.E.; Greef, J. van der; Nesselrooij, J.H.J. van

2003-01-01

Osteoarthritis (OA), one of the most common diseases among the elderly, is characterized by the progressive destruction of joint tissues. Its etiology is largely unclear and no effective disease-modifying treatment is currently available. Metabolic fingerprinting provides a novel tool for the

Lipid metabolism in peroxisomes in relation to human disease

NARCIS (Netherlands)

Wanders, R. J.; Tager, J. M.

1998-01-01

Peroxisomes were long believed to play only a minor role in cellular metabolism but it is now clear that they catalyze a number of important functions. The importance of peroxisomes in humans is stressed by the existence of a group of genetic diseases in man in which one or more peroxisomal

Occult Metabolic Bone Disease in Chronic Pancreatitis | Hari Kumar ...

African Journals Online (AJOL)

Background: Chronic pancreatitis (CP) leads to malabsorption and metabolic bone disease (MBD). Alcoholic CP (ACP) and tropical CP (TCP) are the two common types of CP. Objective: We investigated the presence of occult MBD in patients with CP and compared the same between ACP and TCP. Materials and Methods: ...

Genetic aspects of hypertension and metabolic disease in the obstructive sleep apnoea-hypopnoea syndrome

DEFF Research Database (Denmark)

Riha, R.L.; Diefenbach, K.; Jennum, P.

2008-01-01

Though it has long been recognised that there is a hereditary component to the obstructive steep apnoea/hypopnoea syndrome (OSAHS), identifying its genetic basis remains elusive. Hypertension and metabolic syndrome, Like OSAHS, are polygenic disorders, physiologically complex and the product...... phenotyping, which has hampered genetic dissection of these diseases; in addition, sleep-disordered breathing has not been factored into most studies dealing with essential hypertension or metabolic syndrome. Genome-wide scans have yielded inconsistent results in all three disorders under discussion...... for the expression of cardiovascular disease and metabolic syndrome in the context of OSAHS. (C) 2007 Elsevier Ltd. All rights reserved Udgivelsesdato: 2008/2...

Race and ethnicity, obesity, metabolic health, and risk of cardiovascular disease in postmenopausal women

DEFF Research Database (Denmark)

Schmiegelow, Michelle D; Hedlin, Haley; Mackey, Rachel H

2015-01-01

BACKGROUND: It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups. METHODS AND RESULTS: We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting...... serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m(2)) as normal weight (body mass index 18.5 to obese (body mass index ≥30) and by metabolic health, defined......, overweight women had similar risk to normal weight women (HR 0.92, interaction P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased...

Proton magnetic resonance spectroscopy reflects metabolic decompensation in maple syrup urine disease

International Nuclear Information System (INIS)

Heindel, W.; Kugel, H.; Wendel, U.; Roth, B.; Benz-Bohm, G.

1995-01-01

Using localized proton magnetic resonance spectroscopy ( 1 H-MRS), accumulation of branchedchain amino acids (BCAA) and their corresponding 2-oxo acids (BCOA) could be non-invasively demonstrated in the brain of a 9-year-old girl suffering from classical maple syrup urine disease. During acute metabolic decompensation, the compounds caused a signal at a chemical shift of 0.9 ppm which was assigned by in vitro experiments. The brain tissue concentration of the sum of BCAA and BCOA could be estimated as 0.9 mmol/l. Localized 1 H-MRS of the brain appears to be suitable for examining patients suffering from maple syrup urine disease in different metabolic states. (orig.)

Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

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Bhathena J

2011-06-01

Full Text Available Jasmine Bhathena, Arun Kulamarva, Christopher Martoni, Aleksandra Malgorzata Urbanska, Meenakshi Malhotra, Arghya Paul, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Québec, CanadaBackground: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.Methods: Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.Results: In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed

Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

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Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

2016-03-01

Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility

Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

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Vickram Tejwani

2013-05-01

Full Text Available The elderly chronic kidney disease (CKD population is growing. Both aging and CKD can disrupt calcium (Ca2+ homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD. CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD.

Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

International Nuclear Information System (INIS)

Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

1989-01-01

No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect

Therapeutic Roles of Heme Oxygenase-1 in Metabolic Diseases: Curcumin and Resveratrol Analogues as Possible Inducers of Heme Oxygenase-1

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Yong Son

2013-01-01

Full Text Available Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress, oxidative stress, and endoplasmic reticulum (ER stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1 plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression.

Hyperpolarized metabolic MR in the study of cardiac function and disease

DEFF Research Database (Denmark)

Lauritzen, M. H.; Søgaard, L. V.; Madsen, Pia Lisbeth

2014-01-01

Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR...... signal from a biological molecule of interest by more than 10,000 times, making it possible to measure its cellular uptake and conversion in specific enzymatic pathways in real time. We review the role of hyperpolarized MR in identifying changes in cardiac metabolism in vivo, and present the extensive...... literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating...

Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: which clinical arguments?

Science.gov (United States)

Rosmorduc, Olivier

2013-05-01

Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Proton magnetic resonance spectroscopy reflects metabolic decompensation in maple syrup urine disease

Energy Technology Data Exchange (ETDEWEB)

Heindel, W. [Dept. of Diagnostic Radiology, Univ. Koeln (Germany); Kugel, H. [Dept. of Diagnostic Radiology, Univ. Koeln (Germany); Wendel, U. [Children`s Hospital, Univ. Duesseldorf (Germany); Roth, B. [Children`s Hospital, Univ. Koeln (Germany); Benz-Bohm, G. [Dept. of Diagnostic Radiology, Univ. Koeln (Germany)

1995-06-01

Using localized proton magnetic resonance spectroscopy ({sup 1}H-MRS), accumulation of branchedchain amino acids (BCAA) and their corresponding 2-oxo acids (BCOA) could be non-invasively demonstrated in the brain of a 9-year-old girl suffering from classical maple syrup urine disease. During acute metabolic decompensation, the compounds caused a signal at a chemical shift of 0.9 ppm which was assigned by in vitro experiments. The brain tissue concentration of the sum of BCAA and BCOA could be estimated as 0.9 mmol/l. Localized {sup 1}H-MRS of the brain appears to be suitable for examining patients suffering from maple syrup urine disease in different metabolic states. (orig.)

Population newborn screening for inherited metabolic disease: current UK perspectives.

Science.gov (United States)

Green, A; Pollitt, R J

1999-06-01

Some of the generally accepted criteria for screening programmes are inappropriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application of such criteria creates special difficulties for screening by tandem mass spectrometry, which can detect a range diseases with widely different natural histories and responsiveness to treatment. Further difficulties arise from increasing demands for direct proof of the effects of screening on long-term morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossible to achieve for such relatively rare diseases. This approach also oversimplifies the complex matrix of costs and benefits of newborn metabolic screening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot studies of screening with existing experience of the natural history, diagnosis, and management of the individual disorders concerned.

Energy metabolism and inflammation in brain aging and Alzheimer's disease.

Science.gov (United States)

Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-11-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Completeness of metabolic disease recordings in Nordic national databases for dairy cows.

Science.gov (United States)

Espetvedt, M N; Wolff, C; Rintakoski, S; Lind, A; Østerås, O

2012-06-01

The four Nordic countries Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) all have national databases where diagnostic events in dairy cows are recorded. Comparing and looking at differences in disease occurrence between countries may give information on factors that influence disease occurrence, optimal diseases control and treatment strategies. For such comparisons to be valid, the data in these databases should be standardised and of good quality. The objective of the study presented here was to assess the quality of metabolic disease recordings, primarily milk fever and ketosis, in four Nordic national databases. Completeness of recording figures of database registrations at two different levels was chosen as a measure of data quality. Firstly, completeness of recording of all disease events on a farm regardless of veterinary involvement, called 'Farmer observed completeness', was determined. Secondly, completeness of recording of veterinary treated disease events only, called 'Veterinary treated completeness', was determined. To collect data for calculating these completeness levels a simple random sample of herds was obtained in each country. Farmers who were willing to participate, recorded for 4 months in 2008, on a purpose made registration form, any observed illness in cows, regardless of veterinary involvement. The number of participating herds was 105, 167, 179 and 129 in DK, FI, NO and SE respectively. In total these herds registered 247, 248, 177 and 218 metabolic events for analysis in DK, FI, NO and SE, respectively. Data from national databases were subsequently extracted, and the two sources of data were matched to find the proportion, or completeness, of diagnostic events registered by farmers that also existed in national databases. Matching was done using a common diagnostic code system and allowed for a discrepancy of 7 days for registered date of the event. For milk fever, the Farmer observed completeness was 77%, 67%, 79% and 79

Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

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Monique E. Francois

2017-10-01

Full Text Available Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

Science.gov (United States)

Francois, Monique E; Gillen, Jenna B; Little, Jonathan P

2017-01-01

Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT) have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

Science.gov (United States)

Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

2014-01-01

Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA-Seq

Science.gov (United States)

2017-09-01

AWARD NUMBER: W81XWH-15-1-0251 TITLE: “Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA...Heterogeneity in Metabolic Disease Using Single- Cell RNA-Seq 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Linus Tzu-Yen...ABSTRACT We have developed a robust protocol to generate single cell transcriptional profiles from subcutaneous adipose tissue samples of both human

Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring

Science.gov (United States)

Glastras, Sarah J.; Chen, Hui; Pollock, Carol A.; Saad, Sonia

2018-01-01

Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all the different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk. Evidence suggests a strong link between the intrauterine environment and disease programming. The current review will describe the importance of the intrauterine environment in the development of metabolic disease, including kidney disease. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. The evidence for the role of maternal obesity in the developmental programming of CKD is derived mostly from our rodent models which will be described. The clinical implication of such findings will also be discussed. PMID:29483369

Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD

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Ali Saeed

2017-12-01

Full Text Available Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A’s functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs and retinoid X receptors (RXRs.The liver plays a central role in vitamin A metabolism: (1 it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2 it produces retinol binding protein 4 (RBP4 that distributes vitamin A, as retinol, to peripheral tissues; and (3 it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs. In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH; it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M is the most prominent

Metabolic syndrome and dementia associated with Parkinson's disease: impact of age and hypertension

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Arthur Oscar Schelp

2012-02-01

Full Text Available OBJECTIVE: To determine correlations between age and metabolic disorders in Parkinson's disease (PD patients. METHODS: This observational cross-sectional study included brief tests for dementia and the Mattis test. Signals of metabolic syndrome were evaluated. RESULTS: There was no significant effect from the presence of hypertension (OR=2.36 for patients under 65 years old and OR=0.64 for patients over 65, diabetes or hypercholesterolemia regarding occurrences of dementia associated with PD (24% of the patients. The study demonstrated that each year of age increased the estimated risk of dementia in PD patients by 9% (OR=1.09; 95%CI: 1.01-1.17. CONCLUSION: There was no evidence to correlate the presence of metabolic syndrome with the risk of dementia that was associated with PD. The study confirmed that dementia in PD is age dependent and not related to disease duration.

Pathophysiology and therapeutics of cardiovascular disease in metabolic syndrome.

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Wang, Yabin; Yu, Qiujun; Chen, Yundai; Cao, Feng

2013-01-01

The metabolic syndrome (MetS) is characterized by a cluster of cardiovascular risk factors, including central obesity, hyperglycemia, dyslipidemia and hypertension, which are highly associated with increased morbidity and mortality of cardiovascular diseases (CVD). The association between these metabolic disorders and the development of CVD is believed to be multifactorial, where insulin resistance, oxidative stress, low-grade inflammation and vascular maladaptation act as the major contributors. Therefore, multipronged therapeutic strategies should be taken for the management of patients with MetS. Lifestyle changes including weight control, healthy heart diet and regular exercises have been proposed as first line treatment to decrease CVD risks in MetS individuals. In addition, improving insulin resistance and glucose metabolism, controlling blood pressure as well as modulating dyslipidemia can also delay or reverse the progression of CVD in MetS. This review will first address the complicated interactions between MetS and CVD¸ followed by discussion about the optimal strategy in the prevention and treatment of CVD in MetS patients and the updated results from newly released clinical trials.

The consequences of chronic kidney disease on bone metabolism and growth in children.

Science.gov (United States)

Bacchetta, Justine; Harambat, Jérôme; Cochat, Pierre; Salusky, Isidro B; Wesseling-Perry, Katherine

2012-08-01

Growth retardation, decreased final height and renal osteodystrophy (ROD) are common complications of childhood chronic kidney disease (CKD), resulting from a combination of abnormalities in the growth hormone (GH) axis, vitamin D deficiency, hyperparathyroidism, hypogonadism, inadequate nutrition, cachexia and drug toxicity. The impact of CKD-associated bone and mineral disorders (CKD-MBD) may be immediate (serum phosphate/calcium disequilibrium) or delayed (poor growth, ROD, fractures, vascular calcifications, increased morbidity and mortality). In 2012, the clinical management of CKD-MBD in children needs to focus on three main objectives: (i) to provide an optimal growth in order to maximize the final height with an early management with recombinant GH therapy when required, (ii) to equilibrate calcium/phosphate metabolism so as to obtain acceptable bone quality and cardiovascular status and (iii) to correct all metabolic and clinical abnormalities that can worsen bone disease, growth and cardiovascular disease, i.e. metabolic acidosis, anaemia, malnutrition and 25(OH)vitamin D deficiency. The aim of this review is to provide an overview of the mineral, bone and vascular abnormalities associated with CKD in children in terms of pathophysiology, diagnosis and clinical management.

Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer’s disease

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Madison, Cindee; Baker, Suzanne; Rabinovici, Gil; Jagust, William

2016-01-01

Abstract See Hansson and Gouras (doi:10.1093/aww146) for a scientific commentary on this article. Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer’s disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer’s disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer’s disease-related hypometabolism. Nine healthy young adults (age range: 20–30), 96 cognitively normal older adults (age range: 61–96), and 20 patients with Alzheimer’s disease (age range: 50–90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P glucose metabolism regions defined in young adults (T = 2.05, P glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose

Epicardial adipose tissue in endocrine and metabolic diseases.

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Iacobellis, Gianluca

2014-05-01

Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study.

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Firbank, M J; Yarnall, A J; Lawson, R A; Duncan, G W; Khoo, T K; Petrides, G S; O'Brien, J T; Barker, R A; Maxwell, R J; Brooks, D J; Burn, D J

2017-04-01

To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score. Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Lipid metabolism in the heart. Contribution of BMIPP to the diseased heart

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Nohara, Ryuji [Tazuke Kofukai Medical Research Inst., Osaka (Japan). Kitano Hospital

2001-10-01

Lipid contributes greatly in cardiac metabolism to produce high energy ATPs, and is suggested to be related to the progression and deterioration of heart disease. It is fortunate that the I-123-betamethyliodophenylpentadecanoic acid (BMIPP) imaging technique is now available in determining heart condition, but we must be cautious about the interpretation of images obtained with new tracer. From the uptake of BMIPP into the cell to breakdown and catabolism of it, there exist so many critical enzymatical pathways relating to the modification of BMIPP imaging. In clinical evaluation, the image will be translated as the integral effects of these pathways. In order words, we must be aware of these critical pathways regulating lipid metabolism and modifying factors in order to correctly understand BMIPP imaging. Lipid transport is affected by the albumin/FFA ratio in the blood, and extraction with membrane transporter proteins. Fatty acid binding protein (FABP) in the cytosole will play an important role in regulating lipid flux and following metabolism. Lipid will be utilized either for oxidation, triglyceride or phospholipid formation. For oxidation, carnitine palmitoil transferase is the key enzyme for the entrance of lipid into mitochondria, and oxidative enzymes such as acyl CoA dehydrogenase (MCAD, LCAD, HAD) will determine lipid use for the TCA cycle. ATPs produced in the mitochondria again limit the TG store. It is well known that BMIPP imaging completely changes in the ischemic condition, and is also shown that lipid metabolical regulation completely differs from normal in the very early phase of cardiac hypertrophy. In the process of deteriorating heart failure, metabolical switching of lipid with glucose will take place. In such a different heart disease conditions, it is clear that lipid metabolical regulation, including many lipid enzymes, works differently from in the healthy condition. These lipid enzymes are regulated by nuclear factor peroxisome

The significance of adiponectin as a biomarker in metabolic syndrome and/or coronary artery disease.

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Stojanović, Sanja; Ilić, Marina Deijanin; Ilić, Stevan; Petrović, Dejan; Djukić, Svetlana

2015-09-01

BACKGROUND/AIM. Adiponectin exerts profound protective actions during insulin resistence or prediabetes progression towards more severe clinical entities such as metabolic syndrome and/or cardiovascular disease. Since hypoadiponectinaemia contributes to the pathophysiology of the metabolic syndrome and coronary artery disease the level of circulating adiponectin may be an early marker of cardiovascular events. The aim of this study was to determine the relationships between serum adiponectin levels and parameters of both insulin sensitivity and obesity in patients with the metabolic syndrome and/or coronary artery disease, as well as to assess predictive value of adiponectin serum levels as a biomarker of these entitetis. The study included 100 patients with metabolic syndrome and/or coronary artery disease with different degree of insulin resistance and healthy, normoglycemic individuals. The control group comprising healthy, normoglycemic individuals was used for comparison. Serum level of adiponectin, fasting glucose, fasting insulinemia Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index and anthropometric parameters were determined in all the subjects. Adiponectin was measured by using the ultrasensitive ELISA method. Insulinemia was measured by the radioimmunoassay (RIA) method. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test (OGTT). Results. Adiponectin level was inversely correlated with age (ρ = -0.015), parameters of both obesity (R = 0.437;p insulin resistance (R = 0.374; p insulin resistance. Most importantly, a statistically significant rapid decrease ih adiponectin was in the prediabetic stages (p < 0.01). The predictor value of adiponectin was 1,356.32 ± 402.65 pg/mL. The obtained resultats suggest that adiponectin may be a useful marker in identification of individuals with risk of developing metabolic syndrome and coronary artery disease, as well as a predictor of prediabetes.

The significance of adiponectin as a biomarker in metabolic syndrome and/or coronary artery disease

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Stojanović Sanja

2015-01-01

Full Text Available Introduction/Aim. Adiponectin exerts profound protective actions during insulin resistence or prediabetes progression towards more severe clinical entities such as metabolic syndrome and/or cardiovascular disease. Since hypoadiponectinaemia contributes to the pathophysiology of the metabolic syndrome and coronary artery disease the level of circulating adiponectin may be an early marker of cardiovascular events. The aim of this study was to determine the relationships between serum adiponectin levels and parameters of both insulin sensitivity and obesity in patients with the metabolic syndrome and/or coronary artery disease, as well as to assess predictive value of adiponectin serum levels as a biomarker of these entitetis. Methods. The study included 100 patients with metabolic syndrome and/or coronary artery disease with different degree of insulin resistance and healthy, normoglycemic individuals. The control group comprising healthy, normoglycemic individuals was used for comparison. Serum level of adiponectin, fasting glucose, fasting insulinemia Homeostasis Model Assessment of Insulin Resistance (HOMAIR index and anthropometric parameters were determined in all the subjects. Adiponectin was measured by using the ultrasensitive ELISA method. Insulinemia was measured by the radioimmunoassay (RIA method. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test (OGTT. Results. Adiponectin level was inversely correlated with age (ρ = - 0.015, parameters of both obesity (R = 0.437; p < 0.001 and insulin resistance (R = 0.374; p < 0.01. Decreasing in the level of adiponectin was strongly implicated in the development of insulin resistance. Most importantly, a statistically significant rapid decrease in adiponectin was in the prediabetic stages (p < 0.01. The predictor value of adiponectin was 1,356.32 ± 402.65 рg/mL. Conclusions. The obtained resultats suggest that adiponectin may be a useful marker in

Metabolic flexibility as an adaptation to energy resources and requirements in health and disease.

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Smith, Reuben L; Soeters, Maarten R; Wüst, Rob C I; Houtkooper, Riekelt H

2018-04-24

The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways which is regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors like dietary composition and feeding frequency, exercise training, and use of pharmacological compounds influence metabolic flexibility and will be discussed here. Lastly, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.

Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

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Matsuda, Hiroshi [National Center of Neurology and Psychiatry, Kodaira, Tokyo (Japan). National Center Hospital for Mental, Nervous, and Muscular Disorders

2001-04-01

In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOE{epsilon}4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the {epsilon}4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single {epsilon}4 allele. On the contrary the relation of {epsilon}4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection

Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

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Skene, Debra J.; Middleton, Benita; Fraser, Cara K.; Pennings, Jeroen L. A.; Kuchel, Timothy R.; Rudiger, Skye R.; Bawden, C. Simon; Morton, A. Jennifer

2017-01-01

The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients. PMID:28223686

Patients with psoriasis have insufficient knowledge of their risk of atherothrombotic disease and metabolic syndrome

DEFF Research Database (Denmark)

Skiveren, J; Philipsen, P; Therming, Gitte

2015-01-01

BACKGROUND: Knowledge is crucial to allow patients to increase their level of self-care. OBJECTIVES: To examine the extent to which patients with moderate to severe psoriasis feel informed about their disease, to investigate their level of knowledge about psoriasis and the associated risk...... to a questionnaire. RESULTS: Patients were well informed about their skin disease, but were less well informed about their risk of atherothrombotic disease/metabolic syndrome (visual analogue scale values of 6.91 and 5.15, respectively). Patients' knowledge of the disease was reflected by 74.2-99.1% correct answers...... (CA). The risk of arthritis elicited 88% CA and of depression 41.7% CA, while the risk of atherothrombotic disease and metabolic syndrome produced only 11.9-15.3% CA. Patients treated with biological drugs had a significantly stronger sense of being more well informed about the risk of disease (P = 0...

Police trauma and cardiovascular disease: association between PTSD symptoms and metabolic syndrome.

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Violanti, John M; Fekedulegn, Desta; Hartley, Tara A; Andrew, Michael E; Charles, Luenda E; Mnatsakanova, Anna; Burchfiel, Cecil M

2006-01-01

Although prior evidence exists concerning the association between posttraumatic stress disorder (PTSD) and cardiovascular disease, few studies have examined associations of PTSD symptomatology and the metabolic syndrome in the high stress occupation of police work. The metabolic syndrome is a clustering of cardiovascular disease risk factors that have also been independently associated with psychological conditions. The aim of this study was to examine associations between the PTSD symptoms and metabolic syndrome in police officers. A stratified sample of 115 police officers was randomly selected from the Buffalo, NY Police Department. PTSD symptoms were measured with the Impact of Event scale (IES), divided into categories of subclinical, mild, moderate and severe symptom levels. The metabolic syndrome was considered present if three or more of its component parameters (obesity, elevated blood pressure, reduced high density lipoprotein (HDL) cholesterol, elevated triglycerides, and abnormal glucose levels) were present in each officer. Results indicated a significantly increased prevalence of the metabolic syndrome among those officers in the severe PTSD symptom category compared with the lowest PTSD severity category (prevalence ratio (PR) = 3.31, 95% C.I. = 1.19 - 9.22). Adjustment for age did not alter the association appreciably (PR = 3.12, 95% C.I. = 1.15 - 8.50). Adjustment for several demographic and lifestyle factors (age, education, smoking, alcohol intake) reduced the magnitude of the prevalence ratio slightly for the severe versus subclinical PTSD category (PR = 2.69, 95% C.I. = 0. 79 - 9.13), with adjustment for age and education accounting for most of the attenuation (PR = 2.71, 95% C.I. = 0.99 - 7.37). Thus, officers with severe PTSD symptoms were approximately three times more likely to have the metabolic syndrome and education may account for some of this association.

Practice Patterns in Screening for Metabolic Disease in Women with PCOS of Diverse Race-Ethnic Backgrounds.

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Mott, Melanie M; Kitos, Nicole R; Coviello, Andrea D

2014-09-01

Women with polycystic ovary syndrome (PCOS) are at high risk for metabolic disorders, which prompted the American Association of Clinical Endocrinologists (AACE) to publish a 2005 position statement recommending screening for metabolic disease.The purposes of the present study were to 1) to examine changes in screening rates for obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), hyperlipidemia (HL), nonalcoholic fatty liver disease (NAFLD), and hypertension (HTN) in women with PCOS after publication of the 2005 AACE position statement and 2) to determine if screening rates and metabolic disorders vary by race-ethnicity. PCOS cases in 2006 (n = 547) and 2011 (n = 1,159) and metabolic disorders were identified by International Classification of Diseases, 9th revision (ICD9) code. Screening rates for metabolic disorders were determined by the presence of blood tests (hemoglobin A1c [HbA1c], lipid profile, alanine aminotransferase/aspartate aminotransferase [ALT/AST]). In 2006, ≤25% of PCOS patients underwent recommended screening tests: HbA1c 18%; lipid profile 11, only HbA1c testing had increased (18% to 21%). Obesity increased from 35% to 40%, while other metabolic disorders remained stable. Black women had the highest rates of obesity and HTN in 2011 (Obesity: Black 48%, Hispanic 44%, White 33%, Other 31%, P1; HTN: Black 18%, Hispanic 9%, White 10%, Other 7%, P1). Blacks and Hispanics were screened more often with ALT/AST testing (Black 27/27%, Hispanic 28/27%, White 23/22%, Other 17/18%, P = .02/.03). Screening rates were higher in the endocrine clinic for all metabolic disorders than in other clinics (P11.

Progranulin: At the interface of neurodegenerative and metabolic diseases

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Nguyen, Andrew D.; Nguyen, Thi A.; Martens, Lauren Herl; Mitic, Laura L.; Farese, Robert V.

2013-01-01

Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor–like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin’s function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic fun...

Nutrition and the science of disease prevention: a systems approach to support metabolic health

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Bennett, Brian J.; Hall, Kevin D.; Hu, Frank B.; McCartney, Anne L.; Roberto, Christina

2017-01-01

Progress in nutritional science, genetics, computer science, and behavioral economics can be leveraged to address the challenge of noncommunicable disease. This report highlights the connection between nutrition and the complex science of preventing disease and discusses the promotion of optimal metabolic health, building on input from several complementary disciplines. The discussion focuses on (1) the basic science of optimal metabolic health, including data from gene–diet interactions, microbiome, and epidemiological research in nutrition, with the goal of defining better targets and interventions, and (2) how nutrition, from pharma to lifestyle, can build on systems science to address complex issues. PMID:26415028

Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

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A.P. Davel

2011-09-01

Full Text Available The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Association between the dietary factors and metabolic syndrome with chronic kidney disease in Chinese adults

OpenAIRE

Bi, Hui; Wu, Yiqing; Zhao, Chunjie; Long, Gang

2014-01-01

Objective: The aim of study was to examine the relationship between the dietary nutrition and the prevalence and risk of renal damage in patients with metabolic syndrome. Methods: 260 patients with metabolic syndrome and chronic renal disease meeting criterion were recruited in this cross-sectional study. Metabolic syndrome was defined according to NCEP-ATPIII guidelines. Food-frequency questionnaire was performed to collect the information on dietary nutrition. Anthropometric measurements, i...

Metabolism of Cartilage Proteoglycans in Health and Disease

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Demitrios H. Vynios

2014-01-01

Full Text Available Cartilage proteoglycans are extracellular macromolecules with complex structure, composed of a core protein onto which a variable number of glycosaminoglycan chains are attached. Their biosynthesis at the glycosaminoglycan level involves a great number of sugar transferases well-orchestrated in Golgi apparatus. Similarly, their degradation, either extracellular or intracellular in lysosomes, involves a large number of hydrolases. A deficiency or malfunction of any of the enzymes participating in cartilage proteoglycan metabolism may lead to severe disease state. This review summarizes the findings regarding this topic.

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

OpenAIRE

Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

2017-01-01

Background Synaptic dysfunction contributes to cognitive impairment in Alzheimer?s disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer?s disease. Methods Thirty-four drug-naive patients with mild Alzheimer?s disease (Mini Mental State Examination score ?20) were enrolled in this exploratory, double-blind, randomized...

Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

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Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-01-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review

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Erdi Sozen

2017-08-01

Full Text Available Endoplasmic reticulum (ER is the major site of protein folding and calcium storage. Beside the role of ER in protein homeostasis, it controls the cholesterol production and lipid-membrane biosynthesis as well as surviving and cell death signaling mechanisms in the cell. It is well-documented that elevated plasma cholesterol induces adverse effects in cardiovascular diseases (CVDs, liver disorders, such as non-alcoholic fatty liver disease (NAFLD, non-alcoholic steatosis hepatitis (NASH, and metabolic diseases which are associated with oxidative and ER stress. Recent animal model and human studies have showed high cholesterol and ER stress as an emerging factors involved in the development of many metabolic diseases. In this review, we will summarize the crucial effects of hypercholesterolemia and ER stress response in the pathogenesis of CVDs, NAFLD/NASH, diabetes and obesity which are major health problems in western countries. Keywords: Endoplasmic reticulum stress, High cholesterol, Cardiovascular diseases, Non-alcoholic fatty liver disease, Non-alcoholic steatosis hepatitis

Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease.

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Volonté, M A; Garibotto, V; Spagnolo, F; Panzacchi, A; Picozzi, P; Franzin, A; Giovannini, E; Leocani, L; Cursi, M; Comi, G; Perani, D

2012-07-01

Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

Endocrine manifestations related to inherited metabolic diseases in adults

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Vantyghem Marie-Christine

2012-01-01

Full Text Available Abstract Most inborn errors of metabolism (IEM are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.. IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects, and metal (hemochromatosis and storage disorders (cystinosis. Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes, whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure, congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last. This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses.

Cerebral blood flow and oxygen metabolism in patients with Parkinson's disease

International Nuclear Information System (INIS)

Kitamura, Shin; Ujike, Takashi; Kuroki, Soemu; Sakamoto, Shizuki; Soeda, Toshiyuki; Terashi, Akiro; Iio, Masaaki.

1988-01-01

The purpose of this study was to determine functional changes in the cerebral cortex and basal ganglia in Parkinson's disease (PD). Cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ) were determined using 0-15 positron emission tomography in 10 PD patients and five age-matched healthy volunteers. There was a tendency among PD patients towards a decreased CBF and CMRO 2 in the cerebral cortex and basal ganglia. These values were significantly lower in the frontal cortex in the PD group than the control group. There was no difference in OEF between the groups. A more decreased cerebral oxygen metabolism was observed in patients staged as severer on the scale of Hoehn and Yahr. There was no correlation between cerebral oxygen metabolism and tremor, rigidity, or bradykinesis. A decreased cerebral oxygen metabolism was associated with mental disorders, such as depression, hallucination, and dementia. These results may provide an important clue for the understanding of mesocortical dopaminergic pathway and the relationship between PD and dementia. (N.K.)

Cerebral blood flow and oxygen metabolism in patients with Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Kitamura, Shin; Ujike, Takashi; Kuroki, Soemu; Sakamoto, Shizuki; Soeda, Toshiyuki; Terashi, Akiro; Iio, Masaaki

1988-10-01

The purpose of this study was to determine functional changes in the cerebral cortex and basal ganglia in Parkinson's disease (PD). Cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO/sub 2/) were determined using 0-15 positron emission tomography in 10 PD patients and five age-matched healthy volunteers. There was a tendency among PD patients towards a decreased CBF and CMRO/sub 2/ in the cerebral cortex and basal ganglia. These values were significantly lower in the frontal cortex in the PD group than the control group. There was no difference in OEF between the groups. A more decreased cerebral oxygen metabolism was observed in patients staged as severer on the scale of Hoehn and Yahr. There was no correlation between cerebral oxygen metabolism and tremor, rigidity, or bradykinesis. A decreased cerebral oxygen metabolism was associated with mental disorders, such as depression, hallucination, and dementia. These results may provide an important clue for the understanding of mesocortical dopaminergic pathway and the relationship between PD and dementia. (N.K.).

Carotid body, insulin and metabolic diseases: unravelling the links

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Silvia V Conde

2014-10-01

Full Text Available The carotid bodies (CB are peripheral chemoreceptors that sense changes in arterial blood O2, CO2 and pH levels. Hypoxia, hypercapnia and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN. CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnoea (OSA is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future.

Values of iodine metabolism biomarkers in assessing the iodine nutrition status in surgically treated patients with thyroid disease.

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Han, Jian-hua; Wu, Lian; Yu, Song-lin; Fang, Hui-ling; Kamg, Wei-ming; Cheng, Xin-qi; Lu, Jie; Yu, Jian-chun; Qiu, Ling

2015-04-01

To assess the clinical application value of iodine metabolism biomarkers in assessing iodine nutrition status in surgically treated patients with thyroid disease. Blood,morning urine and 24-hour urine samples were collected in 31 healthy volunteers and in 30 surgically treated patients with thyroid disease before and after surgery. Iodine concentration was analyzed by inductively coupled plasma mass spectrometry. The iodine metabolism biomarkers including serum iodine (SI), morning urine iodine(UI), morning urine iodine/urine creatinine ratio (UI/UCr), 24-hour urine iodine (24 h UI), and 24-hour urine iodine excretion (24 h UIE) were evaluated in these two groups. In addition, the validation coincidence rate of iodine metabolism biomarkers in healthy volunteers to different reference ranges including World Health Organization, Mayo Clinic, and Quest Diagnostics were calculated. The UI/UCr ratio of pre-operative thyroid disease patients was significantly lower than that of healthy volunteers (P0.05) between these two groups. The SI, UI ,and 24 h UI in postoperative thyroid disease patients were significantly higher than those of the pre-operative patients (all Piodine metabolism biomarkers. The UI/UCr ratio may be used for iodine nutrition evaluation in surgically treated patients with thyroid disease.

LITTLE FISH, BIG DATA: ZEBRAFISH AS A MODEL FOR CARDIOVASCULAR AND METABOLIC DISEASE.

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Gut, Philipp; Reischauer, Sven; Stainier, Didier Y R; Arnaout, Rima

2017-07-01

The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an age of discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantages and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date. Copyright © 2017 the American Physiological Society.

Intervention of pumpkin seed oil on metabolic disease revealed by metabonomics and transcript profile.

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Zhao, Xiu-Ju; Chen, Yu-Lian; Fu, Bing; Zhang, Wen; Liu, Zhiguo; Zhuo, Hexian

2017-03-01

Understanding the metabolic and transcription basis of pumpkin seed oil (PSO) intervention on metabolic disease (MD) is essential to daily nutrition and health. This study analyzed the liver metabolic variations of Wistar rats fed normal diet (CON), high-fat diet (HFD) and high-fat plus PSO diet (PSO) to establish the relationship between the liver metabolite composition/transcript profile and the effects of PSO on MD. By using proton nuclear magnetic resonance spectroscopy together with multivariate data analysis, it was found that, compared with CON rats, HFD rats showed clear dysfunctions of choline metabolism, glucose metabolism and nucleotide and amino acid metabolism. Using quantitative real-time polymerase chain reaction (qPCR), it was found that, compared with HFD rats, PSO rats showed alleviated endoplasmic reticulum stress accompanied by lowered unfolded protein response. These findings provide useful information to understand the metabolic alterations triggered by MD and to evaluate the effects of PSO intervention. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Aerobic-Strength Exercise Improves Metabolism and Clinical State in Parkinson’s Disease Patients

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Patrik Krumpolec

2017-12-01

Full Text Available Regular exercise ameliorates motor symptoms in Parkinson’s disease (PD. Here, we aimed to provide evidence that exercise brings additional benefits to the whole-body metabolism and skeletal muscle molecular and functional characteristics, which might help to explain exercise-induced improvements in the clinical state. 3-months supervised endurance/strength training was performed in early/mid-stage PD patients and age/gender-matched individuals (n = 11/11. The effects of exercise on resting energy expenditure (REE, glucose metabolism, adiposity, and muscle energy metabolism (31P-MRS were evaluated and compared to non-exercising PD patients. Two muscle biopsies were taken to determine intervention-induced changes in fiber type, mitochondrial content, and expression of genes related to muscle energy metabolism, as well as proliferative and regenerative capacity. Exercise improved the clinical disability score (MDS-UPDRS, bradykinesia, balance, walking speed, REE, and glucose metabolism and increased muscle expression of energy sensors (AMPK. However, the exercise-induced increase in muscle mass/strength, mitochondrial content, type II fiber size, and postexercise phosphocreatine (PCr recovery (31P-MRS were found only in controls. Nevertheless, MDS-UPDRS was associated with muscle AMPK and mechano-growth factor (MGF expression. Improvements in fasting glycemia were positively associated with muscle function and the expression of Sirt1 and Cox7a1, and the parameters of fitness/strength were positively associated with the expression of MyHC2, MyHC7, and MGF. Moreover, reduced bradykinesia was associated with better muscle metabolism (maximal oxidative capacity and postexercise PCr recovery; 31P-MRS. Exercise training improved the clinical state in early/mid-stage Parkinson’s disease patients, including motor functions and whole-body metabolism. Although the adaptive response to exercise in PD was different from that of controls, exercise

The interplay between intestinal bacteria and host metabolism in health and disease: lessons from Drosophila melanogaster

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Adam C. N. Wong

2016-03-01

Full Text Available All higher organisms negotiate a truce with their commensal microbes and battle pathogenic microbes on a daily basis. Much attention has been given to the role of the innate immune system in controlling intestinal microbes and to the strategies used by intestinal microbes to overcome the host immune response. However, it is becoming increasingly clear that the metabolisms of intestinal microbes and their hosts are linked and that this interaction is equally important for host health and well-being. For instance, an individual's array of commensal microbes can influence their predisposition to chronic metabolic diseases such as diabetes and obesity. A better understanding of host–microbe metabolic interactions is important in defining the molecular bases of these disorders and could potentially lead to new therapeutic avenues. Key advances in this area have been made using Drosophila melanogaster. Here, we review studies that have explored the impact of both commensal and pathogenic intestinal microbes on Drosophila carbohydrate and lipid metabolism. These studies have helped to elucidate the metabolites produced by intestinal microbes, the intestinal receptors that sense these metabolites, and the signaling pathways through which these metabolites manipulate host metabolism. Furthermore, they suggest that targeting microbial metabolism could represent an effective therapeutic strategy for human metabolic diseases and intestinal infection.

Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools

Directory of Open Access Journals (Sweden)

Adrian Kee Keong Teo

2015-09-01

Major conclusions: hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s underlying diseases such as diabetes and metabolic syndromes. The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease.

Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

Science.gov (United States)

2017-08-31

Metabolism, Inborn Errors; Lipid Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogenin-1 Deficiency (Glycogen Storage Disease Type XV); Carnitine Palmitoyl Transferase 2 Deficiency; VLCAD Deficiency; Medium-chain Acyl-CoA Dehydrogenase Deficiency; Multiple Acyl-CoA Dehydrogenase Deficiency; Carnitine Transporter Deficiency; Neutral Lipid Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Muscle Phosphofructokinase Deficiency; Phosphoglucomutase 1 Deficiency; Phosphoglycerate Mutase Deficiency; Phosphoglycerate Kinase Deficiency; Phosphorylase Kinase Deficiency; Beta Enolase Deficiency; Lactate Dehydrogenase Deficiency; Glycogen Synthase Deficiency

Dietary Omega-3 Fatty Acid Deficiency and High Fructose Intake in the Development of Metabolic Syndrome, Brain Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

Directory of Open Access Journals (Sweden)

Artemis P. Simopoulos

2013-07-01

Full Text Available Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS. Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD, promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health.

Endothelial dysfunction in metabolic diseases: role of oxidation and possible therapeutic employment of N-acetylcysteine.

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Masha, A; Martina, V

2014-01-01

Several metabolic diseases present a high cardiovascular mortality due to endothelial dysfunction consequences. In the last years of the past century, it has come to light that the endothelial cells, previously considered as inert in what regards an eventual secretion activity, play a pivotal role in regulating different aspects of the vascular function (endothelial function). It was clearly demonstrated that the endothelium acts as a real active organ, owning endocrine, paracrine and autocrine modulation activities by means of which it is able to regulate the vascular homeostasis. The present review will investigate the relationship between some metabolic diseases and the endothelial dysfunction and in particular the mechanisms underlying the effects of metabolic pathologies on the endothelium. Furthermore, it will consider the possible therapeutic employment of the N-acetilcysteine in such conditions.

Correlations between abnormal iron metabolism and non-motor symptoms in Parkinson's disease.

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Xu, Wu; Zhi, Yan; Yuan, Yongsheng; Zhang, Bingfeng; Shen, Yuting; Zhang, Hui; Zhang, Kezhong; Xu, Yun

2018-07-01

Despite a growing body of evidence suggests that abnormal iron metabolism plays an important role in the pathogenesis of Parkinson's disease (PD), few studies explored its role in non-motor symptoms (NMS) of PD. The present study aimed to investigate the relationship between abnormal iron metabolism and NMS of PD. Seventy PD patients and 64 healthy controls were consecutively recruited to compare serum iron, ceruloplasmin, ferritin, and transferrin levels. We evaluated five classic NMS, including depression, anxiety, pain, sleep disorder, and autonomic dysfunction in PD patients using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms, respectively. Hierarchical multiple regression analysis was used to investigate the correlations between abnormal iron metabolism and NMS. No differences in serum ceruloplasmin and ferritin levels were examined between PD patients and healthy controls, but we observed significantly decreased serum iron levels and increased serum transferrin levels in PD patients in comparison with healthy controls. After eliminating confounding factors, HAMD scores and HAMA scores were both negatively correlated with serum iron levels and positively correlated with serum transferrin levels. In summary, abnormal iron metabolism might play a crucial role in the pathogenesis of depression and anxiety in PD. Serums levels of iron and transferrin could be peripheral markers for depression and anxiety in PD.

The long noncoding RNA Tug1 connects metabolic changes with kidney disease in podocytes.

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Li, Szu Yuan; Susztak, Katalin

2016-11-01

An increasing amount of evidence suggests that metabolic alterations play a key role in chronic kidney disease (CKD) pathogenesis. In this issue of the JCI, Long et al. report that the long noncoding RNA (lncRNA) taurine-upregulated 1 (Tug1) contributes to CKD development. The authors show that Tug1 regulates mitochondrial function in podocytes by epigenetic targeting of expression of the transcription factor PPARγ coactivator 1α (PGC-1α, encoded by Ppargc1a). Transgenic overexpression of Tug1 specifically in podocytes ameliorated diabetes-induced CKD in mice. Together, these results highlight an important connection between lncRNA-mediated metabolic alterations in podocytes and kidney disease development.

Metabolic imaging using PET

International Nuclear Information System (INIS)

Kudo, Takashi

2007-01-01

There is growing evidence that myocardial metabolism plays a key role not only in ischaemic heart disease but also in a variety of diseases which involve myocardium globally, such as heart failure and diabetes mellitus. Understanding myocardial metabolism in such diseases helps to elucidate the pathophysiology and assists in making therapeutic decisions. As well as providing information on regional changes, PET can deliver quantitative information about both regional and global changes in metabolism. This capability of quantitative measurement is one of the major advantages of PET along with physiological positron tracers, especially relevant in evaluating diseases which involve the whole myocardium. This review discusses major PET tracers for metabolic imaging and their clinical applications and contributions to research regarding ischaemic heart disease and other diseases such as heart failure and diabetic heart disease. Future applications of positron metabolic tracers for the detection of vulnerable plaque are also highlighted briefly. (orig.)

Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

Science.gov (United States)

Manti, Sara; Romano, Claudio; Chirico, Valeria; Filippelli, Martina; Cuppari, Caterina; Loddo, Italia; Salpietro, Carmelo; Arrigo, Teresa

2014-01-01

Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH. PMID:24829591

A role for heme in Alzheimer's disease: Heme binds amyloid β and has altered metabolism

OpenAIRE

Atamna, Hani; Frey, William H.

2004-01-01

Heme is a common factor linking several metabolic perturbations in Alzheimer's disease (AD), including iron metabolism, mitochondrial complex IV, heme oxygenase, and bilirubin. Therefore, we determined whether heme metabolism was altered in temporal lobes obtained at autopsy from AD patients and age-matched nondemented subjects. AD brain demonstrated 2.5-fold more heme-b (P < 0.01) and 26% less heme-a (P = 0.16) compared with controls, resulting in a highly significant 2.9-fold decrease in he...

Radiorespirometric study of carbohydrate metabolism in childhood liver disease

International Nuclear Information System (INIS)

DaCosta, H.; Shreeve, W.W.; Merchant, S.

1976-01-01

The need for a suitable parameter to evaluate patients with chronic liver disease has been felt for some time, especially in order to judge the response to surgical shunts and the influence of certain drugs and diets on the liver. Since the liver is a major organ for carbohydrate metabolism, it was decided to analyze the in vivo oxidation of such substrates as glucose and galactose labeled with 14 C. Moderately advanced ''Indian childhood cirrhosis'' and idiopathic fatty hepatic infiltration were selected to represent diffuse chronic liver disease. Oral administration of 14 C-U-glucose or 14 C-1-galactose was followed by analyses of 14 CO 2 in breath by liquid scintillation counting. Conversion of 14 C-glucose to 14 CO 2 was accelerated by both diseases. On the other hand, oxidation of 14 C-galactose was slowed in fatty infiltration and was markedly subnormal in Indian childhood cirrhosis

Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics-small molecule drug interactions.

Science.gov (United States)

Mallick, Pankajini; Taneja, Guncha; Moorthy, Bhagavatula; Ghose, Romi

2017-06-01

Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment. Areas covered: We will discuss clinical biologics-SMD interaction and regulation of DMEs during infection and inflammatory diseases. Mechanistic studies will be discussed and consequences on biologic-small molecule combination therapy on disease outcome due to changes in drug metabolism will be highlighted. Expert opinion: The involvement of immunomodulatory mediators in biologic-SMDs is well known. Regulatory guidelines recommend appropriate in vitro or in vivo assessments for possible interactions. The role of cytokines in biologic-SMDs has been documented. However, the mechanisms of drug-drug interactions is much more complex, and is probably multi-factorial. Studies aimed at understanding the mechanism by which biologics effect the DMEs during inflammation/infection are clinically important.

Bisphenol A sulfonation is impaired in metabolic and liver disease

International Nuclear Information System (INIS)

Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L.; King, Roberta

2016-01-01

Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results: In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.

Bisphenol A sulfonation is impaired in metabolic and liver disease

Energy Technology Data Exchange (ETDEWEB)

Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L., E-mail: angela_slitt@uri.edu; King, Roberta, E-mail: rking@uri.edu

2016-02-01

Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results: In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.

Peroxisomal β-oxidation regulates whole body metabolism, inflammatory vigor, and pathogenesis of nonalcoholic fatty liver disease

Science.gov (United States)

Moreno-Fernandez, Maria E.; Giles, Daniel A.; Stankiewicz, Traci E.; Sheridan, Rachel; Karns, Rebekah; Cappelletti, Monica; Lampe, Kristin; Mukherjee, Rajib; Sina, Christian; Sallese, Anthony; Bridges, James P.; Hogan, Simon P.; Aronow, Bruce J.; Hoebe, Kasper

2018-01-01

Nonalcoholic fatty liver disease (NAFLD), a metabolic predisposition for development of hepatocellular carcinoma (HCC), represents a disease spectrum ranging from steatosis to steatohepatitis to cirrhosis. Acox1, a rate-limiting enzyme in peroxisomal fatty acid β-oxidation, regulates metabolism, spontaneous hepatic steatosis, and hepatocellular damage over time. However, it is unknown whether Acox1 modulates inflammation relevant to NAFLD pathogenesis or if Acox1-associated metabolic and inflammatory derangements uncover and accelerate potential for NAFLD progression. Here, we show that mice with a point mutation in Acox1 (Acox1Lampe1) exhibited altered cellular metabolism, modified T cell polarization, and exacerbated immune cell inflammatory potential. Further, in context of a brief obesogenic diet stress, NAFLD progression associated with Acox1 mutation resulted in significantly accelerated and exacerbated hepatocellular damage via induction of profound histological changes in hepatocytes, hepatic inflammation, and robust upregulation of gene expression associated with HCC development. Collectively, these data demonstrate that β-oxidation links metabolism and immune responsiveness and that a better understanding of peroxisomal β-oxidation may allow for discovery of mechanisms central for NAFLD progression. PMID:29563328

Metabolism of 25-hydroxyvitamin D in copper-laden rat: A model of Wilson's disease

International Nuclear Information System (INIS)

Carpenter, T.O.; Pendrak, M.L.; Anast, C.S.

1988-01-01

Wilson's disease results in excess tissue accumulation of copper and is often complicated by skeletal and mineral abnormalities. The authors investigated vitamin D metabolism in rats fed a copper-laden diet rendering hepatic copper content comparable with that found in Wilson's disease. Injection of 25-hydroxyvitamin D 3 [25(OH)D 3 ] resulted in reduced 1,25--dihydroxyvitamin D [1,25(OH) 2 D] levels in copper-intoxicated rats. In vitro 25(OH)D-1α-hydroxylase activity was impaired in renal mitochondria from copper-intoxicated animals. Activity was also inhibited in mitochondrial from controls when copper was added to incubation media. Impaired conversion of 25(OH)D to 1,25(OH) 2 D occurs in copper intoxication and suggests that altered vitamin D metabolism is a potential factor in the development of bone and mineral abnormalities in Wilson's disease

Individual and family strengths: an examination of the relation to disease management and metabolic control in youth with type 1 diabetes.

Science.gov (United States)

Mackey, Eleanor Race; Hilliard, Marisa E; Berger, Sarah Shafer; Streisand, Randi; Chen, Rusan; Holmes, Clarissa

2011-12-01

We examined the association of youths' positive qualities, family cohesion, disease management, and metabolic control in Type 1 diabetes. Two-hundred fifty-seven youth-parent dyads completed the Family Cohesion subscale of the Family Environment Scale, the Diabetes Behavior Rating Scale, 24-hour diabetes interview, and youth completed the Positive Qualities subscale of the Youth Self Report (YSR-PQ). Structural equation modeling demonstrated that YSR-PQ scores were associated with metabolic control mediated by associations with more family cohesion and better disease management. That is, youth with higher YSR-PQ scores had more cohesive families, better disease management, and, indirectly, better metabolic control. Family cohesion was indirectly associated with better metabolic control mediated by its association with better disease management, but not mediated by its association with YSR-PQ scores. Youth who reported more positive qualities, as measured by the YSR-PQ subscale, had better disease management and metabolic control through the association with more family cohesion. However, the current results did not support an alternative hypothesis that cohesive families display better diabetes management mediated by higher YSR-PQ scores.

Metabolic syndrome and the development of vascular disease and type 2 diabetes in high-risk patients

NARCIS (Netherlands)

Wassink, A.M.J.

2009-01-01

Abdominal obesity and its associated insulin resistance play a key role in the clustering of vascular risk factors, known as Metabolic Syndrome. Subjects with Metabolic Syndrome are at increased risk for the development of both type 2 diabetes and cardiovascular disease. Type 2 diabetes and

Magnesium and metabolic syndrome: The role of magnesium in health and disease

Science.gov (United States)

Metabolic syndrome is a constellation of conditions associated with elevated risk of diabetes and cardiovascular disease. Magnesium, the fourth most abundant cation in the human body and required in over 300 enzymatic reactions, has been shown in experimental, observational, and clinical studies to ...

High density lipoprotein cholesterol (HDL) metabolism and its role in ischemic heart disease

International Nuclear Information System (INIS)

Pirzado, Z.A.; Sngi, S.A.; Malik, R.

1999-01-01

Case control and prospective epidemiological studies have found a striking, consistently negative association between High Density Lipoprotein(HDL) levels and coronary vascular events. As a results, the genetic and environmental determinants of HDL levels are being studied intensively. These investigations and their potential clinical applications require a fundamental understanding of the structure, function and metabolism of HDL and its components. Of the special interest are the means by which it exerts its apparently protective effect. In this report we characterize the structure of HLD: and describe its compounds, particularly the protein component. We discuss HDL metabolism in light of the relationship of HDL to other lipoprotein classes and relate what little is known of the functions of HDL. We also review the biochemical mechanism by which HDL may protect against cardiovascular disease and discuss further biochemical research that will be necessary for a better understanding of HDL. Interest in HDL has been greatly intensified in recent years, stimulated largely by the finding that HDL is inversely related in HDL has been greatly intensified in recent years, stimulated largely by the finding that HDL is inversely related to coronary artery disease. Case-control and prospective observations of the striking, consistent and independent negative association between HDL levels and coronary vascular events have in turn generated new interest in the structure, composition and metabolism of these fascinating lipoproteins. Several studies carried out in Pakistan also reveal the inverse relation of HDL to IHD/sup 1,2/. This article contains a tremendous amount of information on HDL and its relationship to genetic and environmental factors which should be useful to investigations and clinicians in their evaluation and use of HDL cholesterol measurements to assess hearth disease risk. A knowledge of the structure, function and metabolism of HDL and its components is

Fat metabolism during exercise in patients with McArdle disease

DEFF Research Database (Denmark)

Ørngreen, M C; Jeppesen, T D; Andersen, S Tvede

2009-01-01

carbohydrate oxidation was lower, during exercise in patients with McArdle disease vs healthy controls. We found augmented fat oxidation with the onset of a second wind, but further increases in FFA availability, as exercise continued, did not result in further increases in FAO. CONCLUSION: These results......OBJECTIVE: It is known that muscle phosphorylase deficiency restricts carbohydrate utilization, but the implications for muscle fat metabolism have not been studied. We questioned whether patients with McArdle disease can compensate for the blocked muscle glycogen breakdown by enhancing fat...... indicate that patients with McArdle disease have exaggerated fat oxidation during prolonged, low-intensity exercise and that increased fat oxidation may be an important mechanism of the spontaneous second wind. The fact that increasing availability of free fatty acids with more prolonged exercise did...

What fans the fire: insights into mechanisms of leptin in metabolic syndrome-associated heart diseases.

Science.gov (United States)

Dong, Maolong; Ren, Jun

2014-01-01

Obesity and metabolic syndrome are one of the most devastating risk factors for cardiovascular diseases. The obesity gene product leptin plays a central role in the regulation of food intake and energy expenditure. The physiological and pathophysiological roles of leptin in cardiovascular system have been investigated extensively since its discovery in 1994. In addition to its well-established metabolic effects, more recent evidence have depicted a rather pivotal role of leptin in inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis and tissue remodeling en route to the pathogenesis of type 2 diabetes mellitus, hypertension, atherosclerosis, and insulin resistance. Under physiological condition, leptin is known to reduce appetite, promote energy expenditure, increase sympathetic activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin may regulate cardiac and vascular function through a nitric oxide-dependent mechanism. However, hyperleptinemia usually occurs with progressively increased body weight and metabolic syndrome development, leading to a state of global or selective leptin resistance. Both central and peripheral leptin resistance may be present under pathophysiological conditions such as inflammation, insulin resistance, hyperlipidemia and a cadre of other cardiovascular diseases including hypertension, atherosclerosis, obesity, ischemic heart disease and heart failure. In this review, we will discuss cardiovascular actions of leptin related to various components of metabolic syndrome. Particular emphasis will be given to insights derived from therapeutic interventions with lifestyle modification, cardiovascular drugs, anti-diabetic and anti-obesity drugs.

Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III

DEFF Research Database (Denmark)

Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt

2015-01-01

/kg/min (p = 0.024). Fructose ingestion improved exercise tolerance in the patients. CONCLUSION: Similar to patients with McArdle disease, in whom muscle glycogenolysis is also impaired, GSDIIIa is associated with a reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid......OBJECTIVE: Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness, but we hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic...... myopathy. METHODS: We challenged metabolism with cycle-ergometer exercise and measured substrate turnover and oxidation rates using stable isotope methodology and indirect calorimetry in 3 patients and 6 age-matched controls on 1 day, and examined the effect of fructose ingestion on exercise tolerance...

MetSigDis: a manually curated resource for the metabolic signatures of diseases.

Science.gov (United States)

Cheng, Liang; Yang, Haixiu; Zhao, Hengqiang; Pei, Xiaoya; Shi, Hongbo; Sun, Jie; Zhang, Yunpeng; Wang, Zhenzhen; Zhou, Meng

2017-08-22

Complex diseases cannot be understood only on the basis of single gene, single mRNA transcript or single protein but the effect of their collaborations. The combination consequence in molecular level can be captured by the alterations of metabolites. With the rapidly developing of biomedical instruments and analytical platforms, a large number of metabolite signatures of complex diseases were identified and documented in the literature. Biologists' hardship in the face of this large amount of papers recorded metabolic signatures of experiments' results calls for an automated data repository. Therefore, we developed MetSigDis aiming to provide a comprehensive resource of metabolite alterations in various diseases. MetSigDis is freely available at http://www.bio-annotation.cn/MetSigDis/. By reviewing hundreds of publications, we collected 6849 curated relationships between 2420 metabolites and 129 diseases across eight species involving Homo sapiens and model organisms. All of these relationships were used in constructing a metabolite disease network (MDN). This network displayed scale-free characteristics according to the degree distribution (power-law distribution with R2 = 0.909), and the subnetwork of MDN for interesting diseases and their related metabolites can be visualized in the Web. The common alterations of metabolites reflect the metabolic similarity of diseases, which is measured using Jaccard index. We observed that metabolite-based similar diseases are inclined to share semantic associations of Disease Ontology. A human disease network was then built, where a node represents a disease, and an edge indicates similarity of pair-wise diseases. The network validated the observation that linked diseases based on metabolites should have more overlapped genes. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease

NARCIS (Netherlands)

van Oostrom, JCH; Maguire, RP; Verschuuren-Bemelmans, CC; van der Duin, LV; Pruim, J; Roos, RAC; Leenders, KL

2005-01-01

Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the

A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

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Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

2016-07-01

A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

OpenAIRE

Xu, Jia; Verbrugghe, Adronie; Louren?o, Marta; Janssens, Geert P. J.; Liu, Daisy J. X.; Van de Wiele, Tom; Eeckhaut, Venessa; Van Immerseel, Filip; Van de Maele, Isabel; Niu, Yufeng; Bosch, Guido; Junius, Greet; Wuyts, Brigitte; Hesta, Myriam

2016-01-01

Background Inflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear if this microbial profile can alter the nutrient metabolism of the host. The aim of the present study was to characterize the faecal bacterial profile and functionality as well as to determine host me...

Physical activity and metabolic disease among people with affective disorders: Prevention, management and implementation.

Science.gov (United States)

Vancampfort, Davy; Stubbs, Brendon

2017-12-15

One in ten and one in three of people with affective disorders experience diabetes and metabolic syndrome respectively. Physical activity (PA) and sedentary behaviour (SB) are key risk factors that can ameliorate the risk of metabolic disease among this population. However, PA is often seen as luxury and/or a secondary component within the management of people with affective disorders. The current article provides a non-systematic best-evidence synthesis of the available literature, detailing a number of suggestions for the implementation of PA into clinical practice. Whilst the evidence is unequivocal for the efficacy of PA to prevent and manage metabolic disease in the general population, it is in its infancy in this patient group. Nonetheless, action must be taken now to ensure that PA and reducing SB are given a priority to prevent and manage metabolic diseases and improve wider health outcomes. PA should be treated as a vital sign and all people with affective disorders asked about their activity levels and if appropriate advised to increase this. There is a need for investment in qualified exercise specialists in clinical practice such as physiotherapists to undertake and oversee PA in practice. Behavioural strategies such as the self-determined theory should be employed to encourage adherence. Funding is required to develop the evidence base and elucidate the optimal intervention characteristics. PA interventions should form an integral part of the multidisciplinary management of people with affective disorders and our article outlines the evidence and strategies to implement this in practice. Copyright © 2016 Elsevier B.V. All rights reserved.

Abnormal metabolism of glycogen phosphate as a cause for Lafora disease.

Science.gov (United States)

Tagliabracci, Vincent S; Girard, Jean Marie; Segvich, Dyann; Meyer, Catalina; Turnbull, Julie; Zhao, Xiaochu; Minassian, Berge A; Depaoli-Roach, Anna A; Roach, Peter J

2008-12-05

Lafora disease is a progressive myoclonus epilepsy with onset in the teenage years followed by neurodegeneration and death within 10 years. A characteristic is the widespread formation of poorly branched, insoluble glycogen-like polymers (polyglucosan) known as Lafora bodies, which accumulate in neurons, muscle, liver, and other tissues. Approximately half of the cases of Lafora disease result from mutations in the EPM2A gene, which encodes laforin, a member of the dual specificity protein phosphatase family that is able to release the small amount of covalent phosphate normally present in glycogen. In studies of Epm2a(-/-) mice that lack laforin, we observed a progressive change in the properties and structure of glycogen that paralleled the formation of Lafora bodies. At three months, glycogen metabolism remained essentially normal, even though the phosphorylation of glycogen has increased 4-fold and causes altered physical properties of the polysaccharide. By 9 months, the glycogen has overaccumulated by 3-fold, has become somewhat more phosphorylated, but, more notably, is now poorly branched, is insoluble in water, and has acquired an abnormal morphology visible by electron microscopy. These glycogen molecules have a tendency to aggregate and can be recovered in the pellet after low speed centrifugation of tissue extracts. The aggregation requires the phosphorylation of glycogen. The aggregrated glycogen sequesters glycogen synthase but not other glycogen metabolizing enzymes. We propose that laforin functions to suppress excessive glycogen phosphorylation and is an essential component of the metabolism of normally structured glycogen.

Dietary fatty acids linking postprandial metabolic response and chronic diseases.

Science.gov (United States)

Ortega, Almudena; Varela, Lourdes M; Bermudez, Beatriz; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

2012-01-01

Chronic diseases are by far one of the main causes of mortality in the world. One of the current global recommendations to counteract disability and premature death resulting from chronic diseases is to decrease the consumption of energy-dense high-fat diets, particularly those rich in saturated fatty acids (SFA). The most effective replacement for SFA in terms of risk factor outcomes for chronic disease are polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). The biochemical basis for healthy benefits of such a dietary pattern has been widely evaluated under fasting conditions. However, the increasing amount of data available from multiple studies suggest that the postprandial state, i.e., "the period that comprises and follows a meal", plays an important, yet underappreciated, role in the genesis of numerous pathological conditions. In this review, the potential of MUFA, PUFA, and SFA to postprandially affect selected metabolic abnormalities related to chronic diseases is discussed.

Identification of altered metabolic pathways in plasma and CSF in mild cognitive impairment and Alzheimer's disease using metabolomics.

Directory of Open Access Journals (Sweden)

Eugenia Trushina

Full Text Available Alzheimer's Disease (AD currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin decades before the onset of dementia, highlighting the urgent need for the development of early diagnostic methods. Compelling data demonstrate that increased levels of amyloid-beta compromise multiple cellular pathways; thus, the investigation of changes in various cellular networks is essential to advance our understanding of early disease mechanisms and to identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach to determine global metabolic changes in plasma and cerebrospinal fluid (CSF from the same individuals with different AD severity. Metabolic profiling detected a total of significantly altered 342 plasma and 351 CSF metabolites, of which 22% were identified. Based on the changes of >150 metabolites, we found 23 altered canonical pathways in plasma and 20 in CSF in mild cognitive impairment (MCI vs. cognitively normal (CN individuals with a false discovery rate <0.05. The number of affected pathways increased with disease severity in both fluids. Lysine metabolism in plasma and the Krebs cycle in CSF were significantly affected in MCI vs. CN. Cholesterol and sphingolipids transport was altered in both CSF and plasma of AD vs. CN. Other 30 canonical pathways significantly disturbed in MCI and AD patients included energy metabolism, Krebs cycle, mitochondrial function, neurotransmitter and amino acid metabolism, and lipid biosynthesis. Pathways in plasma that discriminated between all groups included polyamine, lysine, tryptophan metabolism, and aminoacyl-tRNA biosynthesis; and in CSF involved cortisone and prostaglandin 2 biosynthesis and metabolism. Our data suggest metabolomics could advance our understanding of the early disease mechanisms shared in progression from CN to

An observational study on the association of nonalcoholic fatty liver disease and metabolic syndrome with gall stone disease requiring cholecystectomy.

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Ahmed, Farah; Baloch, Qamaruddin; Memon, Zahid Ali; Ali, Iqra

2017-05-01

Recognition of Non alcoholic fatty liver disease (NAFLD) and metabolic syndrome in patients with gallstones undergoing laparoscopic or open cholecystectomy, along with it we will also study the life style of patients with gall stones. Patients with gallstones have associated NAFLD, with concurrent metabolic syndrome and these ailments share similar factors for example obesity, hypertriglyceridemia and diabetes mellitus. Factors like body mass index, gender, raised lipid levels, use of contraceptives and alcohol and having diabetes, physical inactiveness, multiparous women, water with excessive iron content, metabolic syndrome, and NAFLD are accountable factors for gallstones formation. This was a case series done at Surgical Unit 1 of Civil Hospital Karachi. Selective samples of 88 patients were included. Duration was 3 months. We included both sexes with ultrasound proof of gall stone irrespective of cholecystitis. Excluded patients with history of seropositive viral hepatitis, autoimmune and wilson's disease. As these conditions can act as a confounder to our variables. Nafld was present in 62.5%(n = 55) while 28.4% (n = 25) had metabolic syndrome. 26.94% had BMI less than 18, 32.12 had BMI between 18 and 25 and majority had BMI greater than 25 i.e in 40.93%. Of all 46.6% had a family history of cholelithiasis. Gallstone patients with NAFLD reported about their first degree relative being suffering from cholelithiasis at a significant p-value of 0.034 while this was not significant in cases of metabolic syndrome and the p -value was 0.190. We found association of metabolic syndrome with gallstones and NAFLD. Non alcoholic fatty liver was highly prevalent in our study subjects. Huge percentage of first degree relatives of gall stone patients had gallstones and this relation was more pronounced patients who had associated NAFLD.

An Official American Thoracic Society Workshop Report: Obesity and Metabolism. An Emerging Frontier in Lung Health and Disease.

Science.gov (United States)

Suratt, Benjamin T; Ubags, Niki D J; Rastogi, Deepa; Tantisira, Kelan G; Marsland, Benjamin J; Petrache, Irina; Allen, Janice B; Bates, Jason H T; Holguin, Fernando; McCormack, Meredith C; Michelakis, Evangelos D; Black, Stephen M; Jain, Manu; Mora, Ana L; Natarajan, Viswanathan; Miller, Yury I; Fessler, Michael B; Birukov, Konstantin G; Summer, Ross S; Shore, Stephanie A; Dixon, Anne E

2017-06-01

The world is in the midst of an unprecedented epidemic of obesity. This epidemic has changed the presentation and etiology of common diseases. For example, steatohepatitis, directly attributable to obesity, is now the most common cause of cirrhosis in the United States. Type 2 diabetes is increasingly being diagnosed in children. Pulmonary researchers and clinicians are just beginning to appreciate the impact of obesity and altered metabolism on common pulmonary diseases. Obesity has recently been identified as a major risk factor for the development of asthma and for acute respiratory distress syndrome. Obesity is associated with profound changes in pulmonary physiology, the development of pulmonary hypertension, sleep-disordered breathing, and altered susceptibility to pulmonary infection. In short, obesity is leading to dramatic changes in lung health and disease. Simultaneously, the rapidly developing field of metabolism, including mitochondrial function, is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Altered metabolism can lead to profound changes in both innate and adaptive immunity, as well as the function of structural cells. To address this emerging field, a 3-day meeting on obesity, metabolism, and lung disease was convened in October 2015 to discuss recent findings, foster research initiatives, and ultimately guide clinical care. The major findings arising from this meeting are reported in this document.

A computer model simulating human glucose absorption and metabolism in health and metabolic disease states [version 1; referees: 2 approved, 1 approved with reservations

Directory of Open Access Journals (Sweden)

Richard J. Naftalin

2016-04-01

Full Text Available A computer model designed to simulate integrated glucose-dependent changes in splanchnic blood flow with small intestinal glucose absorption, hormonal and incretin circulation and hepatic and systemic metabolism in health and metabolic diseases e.g. non-alcoholic fatty liver disease, (NAFLD, non-alcoholic steatohepatitis, (NASH and type 2 diabetes mellitus, (T2DM demonstrates how when glucagon-like peptide-1, (GLP-1 is synchronously released into the splanchnic blood during intestinal glucose absorption, it stimulates superior mesenteric arterial (SMA blood flow and by increasing passive intestinal glucose absorption, harmonizes absorption with its distribution and metabolism. GLP-1 also synergises insulin-dependent net hepatic glucose uptake (NHGU. When GLP-1 secretion is deficient post-prandial SMA blood flow is not increased and as NHGU is also reduced, hyperglycaemia follows. Portal venous glucose concentration is also raised, thereby retarding the passive component of intestinal glucose absorption.   Increased pre-hepatic sinusoidal resistance combined with portal hypertension leading to opening of intrahepatic portosystemic collateral vessels are NASH-related mechanical defects that alter the balance between splanchnic and systemic distributions of glucose, hormones and incretins.The model reveals the latent contribution of portosystemic shunting in development of metabolic disease. This diverts splanchnic blood content away from the hepatic sinuses to the systemic circulation, particularly during the glucose absorptive phase of digestion, resulting in inappropriate increases in insulin-dependent systemic glucose metabolism.  This hastens onset of hypoglycaemia and thence hyperglucagonaemia. The model reveals that low rates of GLP-1 secretion, frequently associated with T2DM and NASH, may be also be caused by splanchnic hypoglycaemia, rather than to intrinsic loss of incretin secretory capacity. These findings may have therapeutic

NAD(+) metabolism: A therapeutic target for age-related metabolic disease

NARCIS (Netherlands)

Mouchiroud, Laurent; Houtkooper, Riekelt H.; Auwerx, Johan

2013-01-01

Abstract Nicotinamide adenine dinucleotide (NAD) is a central metabolic cofactor by virtue of its redox capacity, and as such regulates a wealth of metabolic transformations. However, the identification of the longevity protein silent regulator 2 (Sir2), the founding member of the sirtuin protein

TOR, the Gateway to Cellular Metabolism, Cell Growth, and Disease.

Science.gov (United States)

Blenis, John

2017-09-21

Michael N. Hall is this year's recipient of the Lasker Basic Medical Research Award for the identification of the target of rapamycin, TOR. TOR is a master regulator of the cell's growth and metabolic state, and its dysregulation contributes to a variety of diseases, including diabetes, obesity, neurodegenerative disorders, aging, and cancer, making the TOR pathway an attractive therapeutic target. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Association Between Motor Symptoms and Brain Metabolism in Early Huntington Disease.

Science.gov (United States)

Gaura, Véronique; Lavisse, Sonia; Payoux, Pierre; Goldman, Serge; Verny, Christophe; Krystkowiak, Pierre; Damier, Philippe; Supiot, Frédéric; Bachoud-Levi, Anne-Catherine; Remy, Philippe

2017-09-01

Brain hypometabolism is associated with the clinical consequences of the degenerative process, but little is known about regional hypermetabolism, sometimes observed in the brain of patients with clinically manifest Huntington disease (HD). Studying the role of regional hypermetabolism is needed to better understand its interaction with the motor symptoms of the disease. To investigate the association between brain hypometabolism and hypermetabolism with motor scores of patients with early HD. This study started in 2001, and analysis was completed in 2016. Sixty symptomatic patients with HD and 15 healthy age-matched control individuals underwent positron emission tomography to measure cerebral metabolism in this cross-sectional study. They also underwent the Unified Huntington's Disease Rating Scale motor test, and 2 subscores were extracted: (1) a hyperkinetic score, combining dystonia and chorea, and (2) a hypokinetic score, combining bradykinesia and rigidity. Statistical parametric mapping software (SPM5) was used to identify all hypo- and hypermetabolic regions in patients with HD relative to control individuals. Correlation analyses (P motor subscores and brain metabolic values were performed for regions with significant hypometabolism and hypermetabolism. Among 60 patients with HD, 22 were women (36.7%), and the mean (SD) age was 44.6 (7.6) years. Of the 15 control individuals, 7 were women (46.7%), and the mean (SD) age was 42.2 (7.3) years. In statistical parametric mapping, striatal hypometabolism was significantly correlated with the severity of all motor scores. Hypermetabolism was negatively correlated only with hypokinetic scores in the cuneus (z score = 3.95, P motor scores were associated with higher metabolic values in the inferior parietal lobule, anterior cingulate, inferior temporal lobule, the dentate nucleus, and the cerebellar lobules IV/V, VI, and VIII bilaterally corresponding to the motor regions of the cerebellum (z score = 3

Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats.

Science.gov (United States)

Shin, Bae Kun; Kang, Suna; Kim, Da Sol; Park, Sunmin

2018-02-01

Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused with β-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared to the Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly

Genetic Variants of Homocysteine Metabolizing Enzymes and the Risk of Coronary Artery Disease

Czech Academy of Sciences Publication Activity Database

Janošíková, B.; Pavlíková, Markéta; Kocmanová, Dora; Vítová, D.; Veselá, K.; Krupková, L.; Kahleová, R.; Krijt, J.; Kraml, P.; Hyánek, J.; Zvárová, Jana; Anděl, M.; Kožich, V.

2003-01-01

Roč. 79, - (2003), s. 167-175 ISSN 1096-7192 R&D Projects: GA MZd NM26; GA MZd NM6548 Keywords : coronary disease * risk factors * genes * homocysteine * metabolism Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.038, year: 2003

Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease

DEFF Research Database (Denmark)

Finan, Brian; Clemmensen, Christoffer; Zhu, Zhimeng

2016-01-01

Glucagon and thyroid hormone (T3) exhibit therapeutic potential for metabolic disease but also exhibit undesired effects. We achieved synergistic effects of these two hormones and mitigation of their adverse effects by engineering chemical conjugates enabling delivery of both activities within on...

Metabolically Healthy Obesity and Ischemic Heart Disease

DEFF Research Database (Denmark)

Hansen, Louise; Netterstrom, Marie K.; Johansen, Nanna B.

2017-01-01

Context: Recent studies have suggested that a subgroup of obese individuals is not at increased risk of obesity-related complications. This subgroup has been referred to as metabolically healthy obese. Objective: To investigate whether obesity is a risk factor for development of ischemic heart...... risk factors (low high-density lipoprotein cholesterol, elevated blood pressure, triglycerides, and fasting plasma glucose). Metabolically healthy individuals were defined as having no metabolic risk factors, and metabolically unhealthy individuals were defined as having a minimum of one. Main Outcome...... Measures: IHD. Results: During follow-up, 323 participants developed IHD. Metabolically healthy obese men had increased risk of IHD compared with metabolically healthy normal-weight men [hazard ratio (HR), 3.1; 95% confidence interval (CI), 1.1 to 8.2)]. The corresponding results for women were less...

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

NARCIS (Netherlands)

Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

2017-01-01

BACKGROUND: Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients

European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV

NARCIS (Netherlands)

Lundgren, J. D.; Battegay, M.; Behrens, G.; de Wit, S.; Guaraldi, G.; Katlama, C.; Martinez, E.; Nair, D.; Powderly, W. G.; Reiss, P.; Sutinen, J.; Vigano, A.

2008-01-01

BACKGROUND: Metabolic diseases are frequently observed in HIV-infected persons and, as the risk of contracting these diseases is age-related, their prevalence will increase in the future as a consequence of the benefits of antiretroviral therapy (ART). SUMMARY OF GUIDELINES: All HIV-infected persons

Metabolic syndrome, diet and exercise.

Science.gov (United States)

De Sousa, Sunita M C; Norman, Robert J

2016-11-01

Polycystic ovary syndrome (PCOS) is associated with a range of metabolic complications including insulin resistance (IR), obesity, dyslipidaemia, hypertension, obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease. These compound risks result in a high prevalence of metabolic syndrome and possibly increased cardiovascular (CV) disease. As the cardiometabolic risk of PCOS is shared amongst the different diagnostic systems, all women with PCOS should undergo metabolic surveillance though the precise approach differs between guidelines. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease. Issues requiring further research include the natural history of PCOS-associated metabolic disease, absolute CV risk and comparative efficacy of lifestyle interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Insulin resistance and protein energy metabolism in patients with advanced chronic kidney disease.

Science.gov (United States)

Siew, Edward D; Ikizler, Talat Alp

2010-01-01

Insulin resistance (IR), the reciprocal of insulin sensitivity is a known complication of advanced chronic kidney disease (CKD) and is associated with a number of metabolic derangements. The complex metabolic abnormalities observed in CKD such as vitamin D deficiency, obesity, metabolic acidosis, inflammation, and accumulation of "uremic toxins" are believed to contribute to the etiology of IR and acquired defects in the insulin-receptor signaling pathway in this patient population. Only a few investigations have explored the validity of commonly used assessment methods in comparison to gold standard hyperinsulinemic hyperglycemic clamp technique in CKD patients. An important consequence of insulin resistance is its role in the pathogenesis of protein energy wasting, a state of metabolic derangement characterized by loss of somatic and visceral protein stores not entirely accounted for by inadequate nutrient intake. In the general population, insulin resistance has been associated with accelerated protein catabolism. Among end-stage renal disease (ESRD) patients, enhanced muscle protein breakdown has been observed in patients with Type II diabetes compared to ESRD patients without diabetes. In the absence of diabetes mellitus (DM) or severe obesity, insulin resistance is detectable in dialysis patients and strongly associated with increased muscle protein breakdown, primarily mediated by the ubiquitin-proteasome pathway. Recent epidemiological data indicate a survival advantage and better nutritional status in insulin-free Type II DM patients treated with insulin sensitizer thiazolidinediones. Given the high prevalence of protein energy wasting in ESRD and its unequivocal association with adverse clinical outcomes, insulin resistance may represent an important modifiable target for intervention in the ESRD population.

A fresh look at metabolic bone diseases in reptiles and amphibians.

Science.gov (United States)

Klaphake, Eric

2010-09-01

Metabolic bone diseases (MBDs) are a common presenting complaint in reptiles and amphibians to veterinarians; however, understanding of the causes and diagnostic and treatment options is often extrapolated from human or other mammalian medicine models. Although the roles of UV-B, calcium, phosphorus, and cholecalciferol are better understood in some MBDs, there remain many X factors that are not. Likewise, quantitative diagnosis of MBDs has been difficult not only in terms of staging a disease but also regarding whether or not a condition is present. Treatment options also present challenges in corrective husbandry and diet modifications, medication/modality selection, and dosing/regimen parameters. Copyright 2010 Elsevier Inc. All rights reserved.

Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: Consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology

Science.gov (United States)

Gao, Xin; Fan, Jian-Gao

2013-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, affecting 20%–33% of the general population. Large population-based surveys in China indicate a prevalence of approximately 15%–30%. Worldwide, including in China, the prevalence of NAFLD has increased rapidly in parallel with regional trends of obesity, type2 diabetes and metabolic syndrome. In addition, NAFLD has contributed significantly to increased overall, as well as cardiovascular and liver-related, mortality in the general population. In view of rapid advances in research into NAFLD in recent years, this consensus statement provides a brief update on the progress in the field and suggests preferred approaches for the comprehensive management of NAFLD and its related metabolic diseases. PMID:23560695

The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease

Directory of Open Access Journals (Sweden)

Yalin Liao

2016-08-01

Full Text Available RNA functions through the dynamic formation of complexes with RNA-binding proteins (RBPs in all clades of life. We determined the RBP repertoire of beating cardiomyocytic HL-1 cells by jointly employing two in vivo proteomic methods, mRNA interactome capture and RBDmap. Together, these yielded 1,148 RBPs, 391 of which are shared with all other available mammalian RBP repertoires, while 393 are thus far unique to cardiomyocytes. RBDmap further identified 568 regions of RNA contact within 368 RBPs. The cardiomyocyte mRNA interactome composition reflects their unique biology. Proteins with roles in cardiovascular physiology or disease, mitochondrial function, and intermediary metabolism are all highly represented. Notably, we identified 73 metabolic enzymes as RBPs. RNA-enzyme contacts frequently involve Rossmann fold domains with examples in evidence of both, mutual exclusivity of, or compatibility between RNA binding and enzymatic function. Our findings raise the prospect of previously hidden RNA-mediated regulatory interactions among cardiomyocyte gene expression, physiology, and metabolism.

Myocardial Infarction and Ischemic Heart Disease in Overweight and Obesity With and Without Metabolic Syndrome

DEFF Research Database (Denmark)

Thomsen, Mette; Nordestgaard, Børge G

2014-01-01

IMPORTANCE: Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown. OBJECTIVE: To test the hypothesis that overweight and obesity with and without metabolic syndrome...... syndrome. MAIN OUTCOMES AND MEASURES: Hazard ratios for incident MI and IHD according to combinations of BMI category and absence or presence of metabolic syndrome. RESULTS: During a median of 3.6 years' follow-up, we recorded 634 incident MI and 1781 incident IHD events. For MI, multivariable adjusted...... hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 (95% CI, 1.00-1.61) in overweight and 1.88 (95% CI, 1.34-2.63) in obese individuals without metabolic syndrome and 1.39 (95% CI, 0.96-2.02) in normal weight, 1.70 (95% CI, 1.35-2.15) in overweight, and 2.33 (95% CI, 1...

Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

Science.gov (United States)

Xu, Jia; Verbrugghe, Adronie; Lourenço, Marta; Janssens, Geert P J; Liu, Daisy J X; Van de Wiele, Tom; Eeckhaut, Venessa; Van Immerseel, Filip; Van de Maele, Isabel; Niu, Yufeng; Bosch, Guido; Junius, Greet; Wuyts, Brigitte; Hesta, Myriam

2016-06-16

Inflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear if this microbial profile can alter the nutrient metabolism of the host. The aim of the present study was to characterize the faecal bacterial profile and functionality as well as to determine host metabolic changes in IBD dogs. Twenty-three dogs diagnosed with IBD and ten healthy control dogs were included. Dogs with IBD were given a clinical score using the canine chronic enteropathy clinical activity index (CCECAI). Faecal short-chain fatty acids (SCFA) and ammonia concentrations were measured and quantitative PCR was performed. The concentration of plasma amino acids, acylcarnitines, serum folate, cobalamin, and indoxyl sulfate was determined. No significant differences in the abundance of a selection of bacterial groups and fermentation metabolites were observed between the IBD and control groups. However, significant negative correlations were found between CCECAI and the faecal proportion of Lactobacillus as well as between CCECAI and total SCFA concentration. Serum folate and plasma citrulline were decreased and plasma valine was increased in IBD compared to control dogs. Increased plasma free carnitine and total acylcarnitines were observed in IBD compared with control dogs, whereas short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and, methylmalonylcarnitine) to free carnitine ratios decreased. Dogs with IBD had a higher 3-hydroxyisovalerylcarnitine + isovalerylcarnitine to leucine ratio compared to control dogs. Canine IBD induced a wide range of changes in metabolic profile, especially for the plasma concentrations of short-chain acylcarnitines and amino acids, which could have evolved from tissue damage and alteration in host metabolism. In

Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease.

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Alfred N Fonteh

Full Text Available Sphingolipids are important in many brain functions but their role in Alzheimer's disease (AD is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but

Metabolic and hormonal signatures in pre-manifest and manifest Huntington’s disease patients

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Rui eWang

2014-06-01

Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder typified by involuntary body movements, and psychiatric and cognitive abnormalities. Many HD patients also exhibit metabolic changes including progressive weight loss and appetite dysfunction. Here we have investigated metabolic function in pre-manifest and manifest HD subjects to establish an HD subject metabolic hormonal plasma signature. Individuals at risk for HD who have had predictive genetic testing showing the cytosine-adenine-guanine (CAG expansion causative of HD, but who do not yet present signs and symptoms sufficient for the diagnosis of manifest HD are said to be pre-manifest. Pre-manifest and manifest HD patients, as well as both familial and non-familial controls, were evaluated for multiple peripheral metabolism signals including circulating levels of hormones, growth factors, lipids and cytokines. Both pre-manifest and manifest HD subjects exhibited significantly reduced levels of circulating growth factors, including growth hormone and prolactin. HD-related changes in the levels of metabolic hormones such as ghrelin, glucagon and amylin were also observed. Total cholesterol, HDL-C and LDL-C were significantly decreased in HD subjects. C-reactive protein was significantly elevated in pre-manifest HD subjects. The observation of metabolic alterations, even in subjects considered to be in the pre-manifest stage of HD, suggests that in addition, and prior, to overt neuronal damage, HD affects metabolic hormone secretion and energy regulation, which may shed light on pathogenesis, and provide opportunities for biomarker development.

Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

OpenAIRE

Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B.; Lee, Young Mok; Chou, Janice Y.; Byrne, Barry J.; Correia, Catherine E.; Mah, Cathryn S.; Weinstein, David A.; Conlon, Thomas J.

2011-01-01

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size,...

Protein and leucine metabolism in maple syrup urine disease

International Nuclear Information System (INIS)

Thompson, G.N.; Bresson, J.L.; Pacy, P.J.; Bonnefont, J.P.; Walter, J.H.; Leonard, J.V.; Saudubray, J.M.; Halliday, D.

1990-01-01

Constant infusions of [13C]leucine and [2H5]phenylalanine were used to trace leucine and protein kinetics, respectively, in seven children with maple syrup urine disease (MSUD) and eleven controls matched for age and dietary protein intake. Despite significant elevations of plasma leucine (mean 351 mumol/l, range 224-477) in MSUD subjects, mean whole body protein synthesis [3.78 +/- 0.42 (SD) g.kg-1. 24 h-1] and catabolism (4.07 +/- 0.46) were similar to control values (3.69 +/- 0.50 and 4.09 +/- 0.50, respectively). The relationship between phenylalanine and leucine fluxes was also similar in MSUD subjects (mean phenylalanine-leucine flux ratio 0.35 +/- 0.07) and previously reported adult controls (0.33 +/- 0.02). Leucine oxidation was undetectable in four of the MSUD subjects and very low in the other three (less than 4 mumol.kg-1.h-1; controls 13-20). These results show that persistent elevation in leucine concentration has no effect on protein synthesis. The marked disturbance in leucine metabolism in MSUD did not alter the relationship between rates of catabolism of protein to phenylalanine and leucine, which provides further support for the validity of the use of a single amino acid to trace whole body protein metabolism. The minimal leucine oxidation in MSUD differs from findings in other inborn metabolic errors and indicates that in patients with classical MSUD there is no significant route of leucine disposal other than through protein synthesis

Metabolic regulation of inflammation.

Science.gov (United States)

Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

2017-05-01

Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

Clinical research of bone scan characteristics for metabolic bone diseases

International Nuclear Information System (INIS)

Zhu Ruisen; Luo Qiong; Lu Haikui; Chen Libo; Luo Quanyong

2009-01-01

Characteristic images of 99m Tc-MDP bone scintigraphy in patients with metabolic bone diseases (MBD) were analyzed and compared, in an attempt to improve the capability of differential diagnosis in this aspect. A total of 142 cases, clinically confirmed as (MBD), were categorized into six groups: hyperparathyroidism (117), renal osteodystrophy (4), Paget's disease (16), hypophosphatemic osteomalacia (2), Albers-Schonberg disease (2), and Brittle bone disease (1). They were diagnosed clinically or pathologically, and scanned with 99m Tc-MDP bone scintegraphy, from which the 142 MBD cases were classified into 4 types. The cases of Type I had increased amount of 99m Tc-MDP uptake in whole body bones, including hyperparathyroidism, Albers-Schonberg disease, brittle bone disease and renal osteodystrophy. The cases of Type II had high uptake of 99m Tc-MDP in local region of bones, including paget's disease, hypophosphatemic osteomalacia and hyperparathyroidism. A Type I case with pathological fracture or secondary osteopathy was classified as Type III. Type IV cases were in early stage of hyperparathyroidism, with normal bone scan image. Analysis of the characteristics of 99m Tc-MDP bone scintigraphic findings (locations, morphology and intensities) in patients with MBD may be helpful in the differential diagnosis of MBD, in association with the patient's history and X-ray data altogether. (authors)

Albumin metabolism in health and disease

International Nuclear Information System (INIS)

Kirsch, R.E.; Saunders, S.J.; Brock, J.F.

1979-01-01

Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed

Albumin metabolism in health and disease

Energy Technology Data Exchange (ETDEWEB)

Kirsch, R E; Saunders, S J; Brock, J F [Cape Town Univ. (South Africa). Dept. of Medicine

1979-11-24

Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed.

Developmental plasticity and epigenetic mechanisms underpinning metabolic and cardiovascular diseases.

Science.gov (United States)

Low, Felicia M; Gluckman, Peter D; Hanson, Mark A

2011-06-01

The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments. There are now increasing data that these responses are, at least partially, underpinned by epigenetic mechanisms. A mismatch between the early and later-life environments may lead to inappropriate early life-course epigenomic changes that manifest in later life as increased vulnerability to disease. There is also growing evidence for the transgenerational transmission of epigenetic marks. This article reviews the evidence that susceptibility to metabolic and cardiovascular disease in humans is linked to changes in epigenetic marks induced by early-life environmental cues, and discusses the clinical, public health and therapeutic implications that arise.

Metabolic states following accumulation of intracellular aggregates: implications for neurodegenerative diseases.

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Alexei Vazquez

Full Text Available The formation of intracellular aggregates is a common etiology of several neurodegenerative diseases. Mitochondrial defects and oxidative stress has been pointed as the major mechanistic links between the accumulation of intracellular aggregates and cell death. In this work we propose a "metabolic cell death by overcrowding" as an alternative hypothesis. Using a model of neuron metabolism, we predict that as the concentration of protein aggregates increases the neurons transit through three different metabolic phases. The first phase (0-6 mM corresponds with the normal neuron state, where the neuronal activity is sustained by the oxidative phosphorylation of lactate. The second phase (6-8.6 mM is characterized by a mixed utilization of lactate and glucose as energy substrates and a switch from ammonia uptake to ammonia release by neurons. In the third phase (8.6-9.3 mM neurons are predicted to support their energy demands from glycolysis and an alternative pathway for energy generation, involving reactions from serine synthesis, one carbon metabolism and the glycine cleavage system. The model also predicts a decrease in the maximum neuronal capacity for energy generation with increasing the concentration of protein aggregates. Ultimately this maximum capacity becomes zero when the protein aggregates reach a concentration of about 9.3 mM, predicting the cessation of neuronal activity.

Peculiarities of Ischemic Heart Disease Course and Treatment in Patients with Glucose Metabolism Impairment and Diabetes Mellitus

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O.M. Radchenko

2015-09-01

Full Text Available Combination of ischemic heart disease and diabetes mellitus is characterized by certain features of clinical picture and insufficient effectiveness of treatment of ischemic heart disease. With the aim of investigation of pathogenic mechanisms and features of the clinical course of ischemic heart disease associated with glucose homeostasis violation we examined 116 patients (51 women, 65 men, median of age 63 years old with normal regulation of glucose metabolism (NRG, n = 24, changes in fasting glucose (n = 23, violated glucose tolerance (n = 21, combined violation (n = 24 and diabetes mellitus (n = 24. We also conducted their prospective observation for 40 months with the following endpoints — hospitalization because of cardiovascular complications, death from them and the emergence of diabetes. It was established that ischemic heart disease associated with prediabetic disorders and diabetes mellitus has the following peculiarities: earlier clinical manifestation in women; more frequent and severe heart failure; lower tolerance to physical load in patients with angina pectoris; atypical manifestation of ischemic pain: longer attacks, atypical localization or absent pain; frequent combination with arrhythmias and conduction disorders; frequent affection of multiple coronary arteries, which leads to myocardial infarction with complicated course; eccentric type of left ventricle remodeling; significant calcification of mitral and aortic valves of heart. The main principles of treatment of ischemic heart disease: weight loss; active correction of glucose metabolism violations using medications (metformin even at the stage of prediabetes, because in chronic stable forms of ischemic heart disease metformin significantly improves glucose metabolism, decreases insulin resistance and does not increase the incidence of cardiovascular complications and decompensations of heart failure; the basic drugs for treatment of ischemic heart disease should be

The prevalence of stunting, overweight and obesity, and metabolic disease risk in rural South African children

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Dunger David B

2010-03-01

Full Text Available Abstract Background Low- to middle-income countries are undergoing a health transition with non-communicable diseases contributing substantially to disease burden, despite persistence of undernutrition and infectious diseases. This study aimed to investigate the prevalence and patterns of stunting and overweight/obesity, and hence risk for metabolic disease, in a group of children and adolescents in rural South Africa. Methods A cross-sectional growth survey was conducted involving 3511 children and adolescents 1-20 years, selected through stratified random sampling from a previously enumerated population living in Agincourt sub-district, Mpumalanga Province, South Africa. Anthropometric measurements including height, weight and waist circumference were taken using standard procedures. Tanner pubertal assessment was conducted among adolescents 9-20 years. Growth z-scores were generated using 2006 WHO standards for children up to five years and 1977 NCHS/WHO reference for older children. Overweight and obesity for those 2 for overweight and obesity respectively were used for those ≥ 18 years. Waist circumference cut-offs of ≥ 94 cm for males and ≥ 80 cm for females and waist-to-height ratio of 0.5 for both sexes were used to determine metabolic disease risk in adolescents. Results About one in five children aged 1-4 years was stunted; one in three of those aged one year. Concurrently, the prevalence of combined overweight and obesity, almost non-existent in boys, was substantial among adolescent girls, increasing with age and reaching approximately 20-25% in late adolescence. Central obesity was prevalent among adolescent girls, increasing with sexual maturation and reaching a peak of 35% at Tanner Stage 5, indicating increased risk for metabolic disease. Conclusions The study highlights that in transitional societies, early stunting and adolescent obesity may co-exist in the same socio-geographic population. It is likely that this profile

Potential Linkage Between Cerebrovascular Diseases and Metabolic Syndrome.

Science.gov (United States)

Jabir, Nasimudeen R; Firoz, Chelapram Kandy; Khan, Mohd Shahnawaz; Zaidi, Syed Kashif; Ashraf, Ghulam Md; Shakil, Shazi; Kamal, Mohammad Amjad; Tabrez, Shams

2017-01-01

Cerebrovascular disease (CD) and metabolic syndrome (MetS) are two devastating health dilemma that continues to be a potential contributor to disability and mortality in human population all across the world. Scientific data clearly shows several mechanistic similarities between these two co-existing and interlinked conditions. The linkage exacerbates ongoing patho-physiological condition towards more lethal events. In view of the presence of modifiable risk factors in both CD and MetS, their management holds potential therapeutic value. Hence, developing common treatment strategies for these diseases could involve common molecular agents. In this communication, we have summarized some of the common pathological conditions viz. abdominal obesity, insulin resistance, dyslipidemia, hypertension, and endothelial dysfunction that further deteriorate existing homeostasis in CD and MetS. Based on our article, it is advocated that substantial improvements in novel multi-targeted drug discovery could provide the effective treatment methods in order to avoid the fatal complications related with CD and MetS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington's disease.

Science.gov (United States)

Krzysztoń-Russjan, Jolanta

2016-12-30

Huntington's disease (HD) is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT) is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS) and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described. They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD. Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

Peroxisomes, lipid metabolism, and human disease

NARCIS (Netherlands)

Wanders, R. J.

2000-01-01

In the past few years, much has been learned about the metabolic functions of peroxisomes. These studies have shown that peroxisomes play a major role in lipid metabolism, including fatty acid beta-oxidation, etherphospholipid biosynthesis, and phytanic acid alpha-oxidation. This article describes

Genetic Manipulations of PPARs: Effects on Obesity and Metabolic Disease

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Yaacov Barak

2007-01-01

Full Text Available The interest in genetic manipulations of PPARs is as old as their discovery as receptors of ligands with beneficial clinical activities. Considering the effects of PPAR ligands on critical aspects of systemic physiology, including obesity, lipid metabolism, insulin resistance, and diabetes, gene knockout (KO in mice is the ideal platform for both hypothesis testing and discovery of new PPAR functions in vivo. With the fervent pursuit of the magic bullet to eradicate the obesity epidemic, special emphasis has been placed on the impacts of PPARs on obesity and its associated diseases. As detailed in this review, understanding how PPARs regulate gene expression and basic metabolic pathways is a necessary intermediate en route to deciphering their effects on obesity. Over a decade and dozens of genetic modifications of PPARs into this effort, valuable lessons have been learned, but we are left with more questions to be answered. These lessons and future prospects are the subject of this review.

The insulin-like growth factor I system: physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome.

Science.gov (United States)

Ren, Jun; Anversa, Piero

2015-02-15

Metabolic syndrome is a cluster of risk factors including obesity, dyslipidemia, hypertension, and insulin resistance. A number of theories have been speculated for the pathogenesis of metabolic syndrome including impaired glucose and lipid metabolism, lipotoxicity, oxidative stress, interrupted neurohormonal regulation and compromised intracellular Ca(2+) handling. Recent evidence has revealed that adults with severe growth hormone (GH) and insulin-like growth factor I (IGF-1) deficiency such as Laron syndrome display increased risk of stroke and cardiovascular diseases. IGF-1 signaling may regulate contractility, metabolism, hypertrophy, apoptosis, autophagy, stem cell regeneration and senescence in the heart to maintain cardiac homeostasis. An inverse relationship between plasma IGF-1 levels and prevalence of metabolic syndrome as well as associated cardiovascular complications has been identified, suggesting the clinical promises of IGF-1 analogues or IGF-1 receptor activation in the management of metabolic and cardiovascular diseases. However, the underlying pathophysiological mechanisms between IGF-1 and metabolic syndrome are still poorly understood. This mini-review will discuss the role of IGF-1 signaling cascade in the prevalence of metabolic syndrome in particular the susceptibility to overnutrition and sedentary life style-induced obesity, dyslipidemia, insulin resistance and other features of metabolic syndrome. Special attention will be dedicated in IGF-1-associated changes in cardiac responses in various metabolic syndrome components such as insulin resistance, obesity, hypertension and dyslipidemia. The potential risk of IGF-1 and IGF-1R stimulation such as tumorigenesis is discussed. Therapeutic promises of IGF-1 and IGF-1 analogues including mecasermin, mecasermin rinfabate and PEGylated IGF-1 will be discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

GGDonto ontology as a knowledge-base for genetic diseases and disorders of glycan metabolism and their causative genes.

Science.gov (United States)

Solovieva, Elena; Shikanai, Toshihide; Fujita, Noriaki; Narimatsu, Hisashi

2018-04-18

Inherited mutations in glyco-related genes can affect the biosynthesis and degradation of glycans and result in severe genetic diseases and disorders. The Glyco-Disease Genes Database (GDGDB), which provides information about these diseases and disorders as well as their causative genes, has been developed by the Research Center for Medical Glycoscience (RCMG) and released in April 2010. GDGDB currently provides information on about 80 genetic diseases and disorders caused by single-gene mutations in glyco-related genes. Many biomedical resources provide information about genetic disorders and genes involved in their pathogenesis, but resources focused on genetic disorders known to be related to glycan metabolism are lacking. With the aim of providing more comprehensive knowledge on genetic diseases and disorders of glycan biosynthesis and degradation, we enriched the content of the GDGDB database and improved the methods for data representation. We developed the Genetic Glyco-Diseases Ontology (GGDonto) and a RDF/SPARQL-based user interface using Semantic Web technologies. In particular, we represented the GGDonto content using Semantic Web languages, such as RDF, RDFS, SKOS, and OWL, and created an interactive user interface based on SPARQL queries. This user interface provides features to browse the hierarchy of the ontology, view detailed information on diseases and related genes, and find relevant background information. Moreover, it provides the ability to filter and search information by faceted and keyword searches. Focused on the molecular etiology, pathogenesis, and clinical manifestations of genetic diseases and disorders of glycan metabolism and developed as a knowledge-base for this scientific field, GGDonto provides comprehensive information on various topics, including links to aid the integration with other scientific resources. The availability and accessibility of this knowledge will help users better understand how genetic defects impact the

Lack of differential pattern in central adiposity and metabolic syndrome in Barrett's esophagus and gastroesophageal reflux disease.

LENUS (Irish Health Repository)

Healy, L A

2012-02-01

Obesity is an established risk factor for esophageal adenocarcinoma, although the mechanism is unclear. A pathway from reflux to inflammation through metaplasia is the dominant hypothesis, and an added role relating to visceral adiposity and the metabolic syndrome has been mooted in Barrett\\'s esophagus (BE) patients. Whether BE differs from gastroesophageal reflux disease (GERD) in obesity and metabolic syndrome profiles is unclear, and this was the focus of this study. Patients with proven BE or GERD were randomly selected from the unit data registry and invited to attend for metabolic syndrome screening, anthropometry studies including segmental body composition analysis, and laboratory tests including fasting lipids, insulin, and C-reactive protein. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria. One hundred and eighteen BE patients and 113 age- and sex-matched GERD controls were studied. The incidence of obesity (body mass index >30 kg\\/m(2)) was 36% and 38%, respectively, with the pattern of fat deposition predominantly central and an estimated trunk fat mass of 13 and 14 kg, respectively. Using the NCEP criteria, metabolic syndrome was significantly more common in the BE cohort (30% vs 20%, P < 0.05), but there was no significant difference using IDF criteria (42% vs 37%, P= 0.340). Central obesity and the metabolic syndrome are common in both Barrett\\'s and GERD cohorts, but not significantly different, suggesting that central obesity and the metabolic syndrome does not per se impact on the development of BE in a reflux population. In BE, the importance of obesity and the metabolic syndrome in disease progression merits further study.

Skeletal muscle metabolism during prolonged exercise in Pompe disease

DEFF Research Database (Denmark)

Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt

2017-01-01

of exercise, it is important in Pompe disease to acquire more information about muscle substrate use during exercise. METHODS: Seven adults with Pompe disease were matched to a healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak) and (2) carbohydrate and fatty acid metabolism...... during submaximal exercise (33 W) for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable isotopes. RESULTS: In the patients, VO2peak was less than half of average control values; mean difference -1659 mL/min (CI: -2450 to -867, P = 0.001). However, the respiratory exchange ratio...... increased to >1.0 and lactate levels rose 5-fold in the patients, indicating significant glycolytic flux. In line with this, during submaximal exercise, the rates of oxidation (ROX) of carbohydrates and palmitate were similar between patients and controls (mean difference 0.226 g/min (CI: 0.611 to -0.078, P...

Metabolic pattern analysis of early detection in Alzheimer's disease from other types of dementias and correlated with cognitive function

International Nuclear Information System (INIS)

Ju, R. H.; Lee, C. W.; Jung, Y. A.; Sohn, H. S.; Kim, S. H.; Seo, T. S

2004-01-01

PET/CT studies have demonstrated temporoparietal hypometabolism in probable and definite Alzheimer's disease (AD), a pattern that may help differentiate AD from other types of dementias. Seeking to distinguish Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we examined brain glucose metabolism of DLB and AD. Identification of individual differences in patterns of regional cerebral glucose metabolism (rCMRglc) interactions may be important for early detection of AD. We elucidate the relationship between reduced cognitive function and cerebral metabolism. Ten patients with the diagnosis of AD, 3 DLB patients underwent 18F-FDG PET CT. We applied statistical mapping procedure to evaluate the diagnostic power of rCMRglc patterns for differentiation and also correlated with Korean-mini mental status exam (K-MMSE) score include orientation time, place, registration, attention, calculation, recaIl, language and visuospatial function. Glucose metabolic pattern analysis confirmed AD and DLB patients showed significant metabolic reductions involving parietotemporal association, posterior cingulate, and frontal association cortex. DLB patients showed significant metabolic reductions in the occipital cortex, particularly in the primary visual cortex. Covariate analysis revealed that occipital metabolic changes in DLB were independent from those in the adjacent parietotemporal cortices. AnaIysis of clinically diagnosed probable AD patients showed a significantly higher frequency of primary visual metabolic reduction among patients who fulfilled clinical criteria for DLB. occipital hypometabolism is a potential discriminate marker to distinguish DLB versus AD

Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental fatigue of Parkinson disease.

Science.gov (United States)

Zuo, Li-Jun; Yu, Shu-Yang; Hu, Yang; Wang, Fang; Piao, Ying-Shan; Lian, Teng-Hong; Yu, Qiu-Jin; Wang, Rui-Dan; Li, Li-Xia; Guo, Peng; Du, Yang; Zhu, Rong-Yan; Jin, Zhao; Wang, Ya-Jie; Wang, Xiao-Min; Chan, Piu; Chen, Sheng-Di; Wang, Yong-Jun; Zhang, Wei

2016-12-21

Fatigue is a very common non-motor symptom in Parkinson disease (PD) patients. It included physical fatigue and mental fatigue. The potential mechanisms of mental fatigue involving serotonergic dysfunction and abnormal iron metabolism are still unknown. Therefore, we evaluated the fatigue symptoms, classified PD patients into fatigue group and non-fatigue group, and detected the levels of serotonin, iron and related proteins in CSF and serum. In CSF, 5-HT level is significantly decreased and the levels of iron and transferrin are dramatically increased in fatigue group. In fatigue group, mental fatigue score is negatively correlated with 5-HT level in CSF, and positively correlated with the scores of depression and excessive daytime sleepiness, and disease duration, also, mental fatigue is positively correlated with the levels of iron and transferrin in CSF. Transferrin level is negatively correlated with 5-HT level in CSF. In serum, the levels of 5-HT and transferrin are markedly decreased in fatigue group; mental fatigue score exhibits a negative correlation with 5-HT level. Thus serotonin dysfunction in both central and peripheral systems may be correlated with mental fatigue through abnormal iron metabolism. Depression, excessive daytime sleepiness and disease duration were the risk factors for mental fatigue of PD.

Chronic obstructive pulmonary disease may be one of the terminal end points of metabolic syndrome

International Nuclear Information System (INIS)

Helvaci, M.R.; Aydin, L.Y.; Aydin, Y.

2012-01-01

Objective: We tried to understand presence of any effect of excess weight on respiratory system by means of excessive adipose tissue functioning as an endocrine organ and causing a Methodology: Mild (stage 1), moderate (stage 2), and severe (stage 3 and 4) chronic obstructive pulmonary disease (COPD) patients were detected, and compared according to the metabolic parameters in between. Results: There were 145, 56, and 34 patients in the mild, moderate, and severe COPD groups, respectively. The mean age increased gradually (52.4, 56.4, and 60.0 years) from the mild towards the severe COPD groups, respectively (p<0.05 nearly in all steps). Similarly, the mean direction (p<0.05 nearly in all steps). Parallel to them, the mean body mass index increased Conclusion: The metabolic syndrome includes some reversible indicators such as overweight, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, impaired fasting glucose, impaired glucose tolerance, and white coat hypertension for the development of terminal diseases including obesity, hypertension, diabetes mellitus, peripheral artery disease, coronary heart disease, and stroke. In our opinion, COPD may be one of the terminal end points of the syndrome. (author)

Chronic obstructive pulmonary disease may be one of the terminal end points of metabolic syndrome

Energy Technology Data Exchange (ETDEWEB)

Helvaci, M R; Aydin, L Y; Aydin, Y

2012-04-15

Objective: We tried to understand presence of any effect of excess weight on respiratory system by means of excessive adipose tissue functioning as an endocrine organ and causing a Methodology: Mild (stage 1), moderate (stage 2), and severe (stage 3 and 4) chronic obstructive pulmonary disease (COPD) patients were detected, and compared according to the metabolic parameters in between. Results: There were 145, 56, and 34 patients in the mild, moderate, and severe COPD groups, respectively. The mean age increased gradually (52.4, 56.4, and 60.0 years) from the mild towards the severe COPD groups, respectively (p<0.05 nearly in all steps). Similarly, the mean direction (p<0.05 nearly in all steps). Parallel to them, the mean body mass index increased Conclusion: The metabolic syndrome includes some reversible indicators such as overweight, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, impaired fasting glucose, impaired glucose tolerance, and white coat hypertension for the development of terminal diseases including obesity, hypertension, diabetes mellitus, peripheral artery disease, coronary heart disease, and stroke. In our opinion, COPD may be one of the terminal end points of the syndrome. (author)

The shift work and health research agenda: Considering changes in gut microbiota as a pathway linking shift work, sleep loss and circadian misalignment, and metabolic disease.

Science.gov (United States)

Reynolds, Amy C; Paterson, Jessica L; Ferguson, Sally A; Stanley, Dragana; Wright, Kenneth P; Dawson, Drew

2017-08-01

Prevalence and impact of metabolic disease is rising. In particular, overweight and obesity are at epidemic levels and are a leading health concern in the Western world. Shift work increases the risk of overweight and obesity, along with a number of additional metabolic diseases, including metabolic syndrome and type 2 diabetes (T2D). How shift work contributes to metabolic disease has not been fully elucidated. Short sleep duration is associated with metabolic disease and shift workers typically have shorter sleep durations. Short sleep durations have been shown to elicit a physiological stress response, and both physiological and psychological stress disrupt the healthy functioning of the intestinal gut microbiota. Recent findings have shown altered intestinal microbial communities and dysbiosis of the gut microbiota in circadian disrupted mice and jet lagged humans. We hypothesize that sleep and circadian disruption in humans alters the gut microbiota, contributing to an inflammatory state and metabolic disease associated with shift work. A research agenda for exploring the relationship between insufficient sleep, circadian misalignment and the gut microbiota is provided. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolic Syndrome

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Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

Preventive Effect of Pine Bark Extract (Flavangenol on Metabolic Disease in Western Diet-Loaded Tsumura Suzuki Obese Diabetes Mice

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Tsutomu Shimada

2011-01-01

Full Text Available It is known that the metabolic syndrome has a multi-factorial basis involving both genetic and environmental risk factors. In this study, Tsumura Suzuki Obese Diabetes (TSOD mice, a mouse model of multi-factorial, hereditary, obese type II diabetes, were given a Western diet (WTD as an environmental factor to prepare a disease model (TSOD-WTD and to investigate the preventive effects of Pine bark extract (Flavangenol against obesity and various features of metabolic disease appearing in this animal model. In contrast to control Tsumura Suzuki Non-obesity (TSNO mice, TSOD mice were obese and suffered from other metabolic complications. WTD-fed TSOD mice developed additional features such as hyperinsulinemia, abnormal glucose/lipid metabolism and fatty liver. The treatment with Flavangenol had a suppressive effect on increase in body weight and accumulation of visceral and subcutaneous fat, and also showed preventive effects on symptoms related to insulin resistance, abnormal glucose/lipid metabolism and hypertension. Flavangenol also increased the plasma concentration of adiponectin and decreased the plasma concentration of TNF-α. We next investigated the effect of Flavangenol on absorption of meal-derived lipids. Flavangenol suppressed absorption of neutral fat in an olive-oil-loading test (in vivo and showed an inhibitory effect on pancreatic lipase (in vitro. The above results suggest that Flavangenol has a preventive effect on severe metabolic disease due to multiple causes that involve both genetic and environmental risk factors. The mechanism of action might involve a partial suppressive effect of meal-derived lipids on absorption.

Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

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Han, Lianshu; Han, Feng; Ye, Jun; Qiu, Wenjuan; Zhang, Huiwen; Gao, Xiaolan; Wang, Yu; Ji, Wenjun; Gu, Xuefan

2015-03-01

Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants. © 2014 Wiley Periodicals, Inc.

Non-alcoholic Fatty Liver Disease and Metabolic Syndrome in Hypopituitary Patients

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Nyenwe, Ebenezer A; Williamson-Baddorf, Sarah; Waters, Bradford; Wan, Jim Y; Solomon, Solomon S.

2009-01-01

Background Increased incidence of cardiovascular mortality and non-alcoholic fatty liver disease (NAFLD) has been reported in hypopituitarism; but previous studies did not correct for obesity in these patients. Therefore it remained unclear if endocrine deficiency in hypopituitarism is associated with metabolic consequences independent of obesity. This study was designed to determine the burden of cardiovascular disease and NAFLD in hypopituitarism. Methods We performed a retrospective case-control analysis of hypopituitary patients at Veterans Affair Medical center, Memphis; from January 1997- June 2007. After matching for age, gender, obesity and race, relevant data were abstracted from the subjects' records to determine the presence of hypopituitarism, cardiovascular risk factors and fatty liver disease. Cases and controls were characterized by descriptive statistics, and compared using Chi-square and Student's t- tests. Results Hypopituitary patients exhibited higher prevalence of hypertension- 88% vs 78% (P0.3). Hypopituitary patients had higher elevations in serum aminotransferase levels and hyperbilirubinemia-24% vs 11% (Phypopituitarism. Although hypopituitary patients had higher prevalence of cardiovascular risk factors than controls, they were not disproportionately affected by cardiovascular disease. PMID:19745609

Risk of development of chronic kidney disease in patients with type 2 diabetes having metabolic syndrome

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Moin, S.; Gondal, G.M.G.

2008-01-01

To measure the relation of creatinine clearance in type-2 diabetic patients with different components of metabolic syndrome and to quantify the relationship of frequency of incident CKD with increasing number of metabolic syndrome components while controlling for age, gender and duration of diabetes. Cross-sectional descriptive study. Patients having type-2 Diabetes for more than 5 years were enrolled. Information regarding age, gender, duration of diabetes, type of diabetes, treatment taking, complete fasting lipid profile, fasting blood glucose, Body Mass Index (BMI), 24 hours urinary proteins and creatinine clearance, co-existent risk factors like hypertension and ischemic heart disease was taken. Patients were divided into groups having one to all five metabolic syndrome traits. Progressive increase in the metabolic syndrome traits was compared with decline in creatinine clearance. Pearson correlation test and multiple logistic regression were applied to determine correlation with significance at r and p <0.05. Out of 104 evaluated female and male patients, 70% had hypertension, ischemic heart disease and a family history of diabetes. While 20% had normal creatinine clearance, 37% had a creatinine clearance between 60-90 ml/min, 19% had a creatinine clearance of 30-59 ml/min, 18% had a creatinine clearance of less than 30 ml/min and 10% were already in stage 5 CKD. The decline in renal function was more severe in subjects evaluated who had a higher number of features of the metabolic syndrome. Age was the only significant determinant of development of CKD (p=0.05). The renal function progressively declined with 3 or more features of the metabolic syndrome. (author)

Ferrokinetic Parameters and Regulation of Iron Metabolism in Patients with Chronic Inflammatory Bowel Diseases

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T.Y. Boiko

2014-11-01

Full Text Available Article presents parameters of iron metabolism and cytokines (IL-6 and TNF-α in patients with chronic inflammatory bowel diseases (CIBD. The material for the study was the blood of 69 patients with CIBD and anemia and 26 — without anemia. We have studied the features of main ferrokinetic parameters — iron, total iron-binding capacity of serum, transferrin saturation, ferritin, transferrin receptor, erythropoietin, hepcidin depending on hemoglobin level and the type of anemia. The relationship of iron metabolism disorders with the level of proinflammatory cytokines (IL-6 and TNF-α is shown.

Metabolic Syndrome and Chronic Renal Disease

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Vaia D. Raikou

2018-01-01

Full Text Available Background: The influence of metabolic syndrome (MetS on kidneys is related to many complications. We aimed to assess the association between MetS and chronic renal disease defined by a poor estimated glomerular filtration rate (eGFR and/or the presence of microalbuminuria/macroalbuminuria. Methods: 149 patients (77 males/72 females were enrolled in the study. Chronic renal disease was defined according to KDIGO 2012 criteria based on eGFR category and classified albuminuria. MetS was studied as a dichotomous variable (0 to 5 components including hypertension, waist circumference, low HDL-cholesterol, high triglycerides, and high glucose. Results: The association between clustering MetS and both classified eGFR and classified albuminuria (x2 = 50.3, p = 0.001 and x2 = 26.9, p = 0.003 respectively was found to be significant. The MetS presence showed an odds 5.3-fold (1.6–17.8 higher for low eGFR and 3.2-fold (1.2–8.8 higher for albuminuria in combination with the presence of diabetes mellitus, which also increased the risk for albuminuria by 3.5-fold (1.1–11.3. Albuminuria was significantly associated with high triglycerides, hypertension, high glucose (x2 = 11.8, p = 0.003, x2 = 11.4, p = 0.003 and x2 = 9.1, p = 0.01 respectively, and it was mildly associated with a low HDL-C (x2 = 5.7, p = 0.06. A significant association between classified eGFR and both high triglycerides and hypertension (x2 = 9.7, p = 0.04 and x2 = 16.1, p = 0.003 respectively was found. Conclusion: The clustering of MetS was significantly associated with chronic renal disease defined by both classified eGFR and albuminuria. The definition of impaired renal function by classified albuminuria was associated with more MetS components rather than the evaluation of eGFR category. MetS may contribute to the manifestation of albuminuria in patients with diabetes mellitus.

Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

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Fonteh, Alfred N.; Ormseth, Cora; Chiang, Jiarong; Cipolla, Matthew; Arakaki, Xianghong; Harrington, Michael G.

2015-01-01

Sphingolipids are important in many brain functions but their role in Alzheimer’s disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but not impaired

Effect of folic acid on methionine and homocysteine metabolism in end-stage renal disease

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Stam, F.; van Guldener, C.; ter Wee, P.M.; Jakobs, C.A.J.M.; van der Meer, K.; Stehouwer, C.D.A.

2005-01-01

Background. The pathogenesis of hyperhomocysteinemia in end-stage renal disease (ESRD) is unclear. Folic acid lowers, but does not normalize, the plasma homocysteine level in patients with ESRD, but its effect on whole body metabolism of homocysteine is unknown. Methods We studied the effect of 3

Paradigm shift in cancer treatment: Cancer treatment as a metabolic disease – fusion of Eastern and Western medicine

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Reo Hamaguchi

2017-10-01

Full Text Available Current standard therapies for cancer, including surgery, anti-cancer drugs, and radiotherapy, are thought to contribute to the improvement in the survival rates of cancer patients. However, such standard therapies have 3 major problems: in advanced cancers, it is unlikely that standard cancer treatments will cure the disease; adverse side effects that accompany standard cancer treatments put many patients in distress; and a large amount of medical expenditure is required for new and expensive anti-cancer drugs. These problems may be viewed as a result of establishing treatments without any consideration regarding the root cause of the cancer. Otto Warburg suggested that particular changes in the energy metabolism of cells, which are associated with a shortage of oxygen, are the root cause of cancer. Cancer cells have unique metabolic characteristics, and thus we believe that it is important to treat cancer as a metabolic disease. More specifically, not only is it important to suppress cancer cell metabolism, but it is also important to improve the chronic inflammation that is associated with the development and progression of cancer, and to support the functions of immune cells. This type of view of cancer treatment coincides with the principles of Chinese medicine, which has a history of 4000 years, such as “fuzheng quxie” and “zhibing qiuben”, which can assist in the establishment of cancer treatments for patients. In this article, we discuss cancer treatments from the view of cancer as a metabolic disease and their association with Chinese medicine, and introduce some clinical cases along with a review of the literature.

The Role of Peroxisome Proliferator-Activated Receptor β/δ on the Inflammatory Basis of Metabolic Disease

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Teresa Coll

2010-01-01

Full Text Available The pathophysiology underlying several metabolic diseases, such as obesity, type 2 diabetes mellitus, and atherosclerosis, involves a state of chronic low-level inflammation. Evidence is now emerging that the nuclear receptor Peroxisome Proliferator-Activated Receptor (PPARβ/δ ameliorates these pathologies partly through its anti-inflammatory effects. PPARβ/δ activation prevents the production of inflammatory cytokines by adipocytes, and it is involved in the acquisition of the anti-inflammatory phenotype of macrophages infiltrated in adipose tissue. Furthermore, PPARβ/δ ligands prevent fatty acid-induced inflammation in skeletal muscle cells, avoid the development of cardiac hypertrophy, and suppress macrophage-derived inflammation in atherosclerosis. These data are promising and suggest that PPARβ/δ ligands may become a therapeutic option for preventing the inflammatory basis of metabolic diseases.

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial.

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Rijpma, Anne; van der Graaf, Marinette; Lansbergen, Marieke M; Meulenbroek, Olga; Cetinyurek-Yavuz, Aysun; Sijben, John W; Heerschap, Arend; Olde Rikkert, Marcel G M

2017-07-26

Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's disease. Thirty-four drug-naive patients with mild Alzheimer's disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study. Before and after 4-week intervention with Souvenaid or an isocaloric control product, phosphorus and proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo-inositol), and choline metabolism (choline-containing compounds [tCho]). The main outcome parameters were PME and PDE signal intensities and the PME/PDE ratio. MRS data from 33 patients (60-86 years old; 42% males; Souvenaid arm n = 16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks of Souvenaid compared with control (PME/PDE least squares [LS] mean difference [95% CI] 0.18 [0.06-0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00-0.02], p = 0.019). No significant differences were observed in the other MRS outcome parameters. MRS reveals that Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease, in line with findings in preclinical studies. Netherlands Trial Register, NTR3346 . Registered on 13 March 2012.

Thermodynamics in Neurodegenerative Diseases: Interplay Between Canonical WNT/Beta-Catenin Pathway-PPAR Gamma, Energy Metabolism and Circadian Rhythms.

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Vallée, Alexandre; Lecarpentier, Yves; Guillevin, Rémy; Vallée, Jean-Noël

2018-03-23

Entropy production rate is increased by several metabolic and thermodynamics abnormalities in neurodegenerative diseases (NDs). Irreversible processes are quantified by changes in the entropy production rate. This review is focused on the opposing interactions observed in NDs between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In amyotrophic lateral sclerosis and Huntington's disease, WNT/beta-catenin pathway is upregulated, whereas PPAR gamma is downregulated. In Alzheimer's disease and Parkinson's disease, WNT/beta-catenin pathway is downregulated while PPAR gamma is upregulated. The dysregulation of the canonical WNT/beta-catenin pathway is responsible for the modification of thermodynamics behaviors of metabolic enzymes. Upregulation of WNT/beta-catenin pathway leads to aerobic glycolysis, named Warburg effect, through activated enzymes, such as glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactic dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH). Downregulation of WNT/beta-catenin pathway leads to oxidative stress and cell death through inactivation of Glut, PKM2, PDK1, MCT-1, LDH-A but activation of PDH. In addition, in NDs, PPAR gamma is dysregulated, whereas it contributes to the regulation of several key circadian genes. NDs show many dysregulation in the mediation of circadian clock genes and so of circadian rhythms. Thermodynamics rhythms operate far-from-equilibrium and partly regulate interactions between WNT/beta-catenin pathway and PPAR gamma. In NDs, metabolism, thermodynamics and circadian rhythms are tightly interrelated.

Microbial pathways in colonic sulfur metabolism and links with health and disease

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Franck eCarbonero

2012-11-01

Full Text Available Sulfur is both crucial to life and a potential threat to health. While colonic sulfur metabolism mediated by eukaryotic cells is relatively well studied, much less is known about sulfur metabolism within gastrointestinal microbes. Sulfated compounds in the colon are either of inorganic (e.g., sulfates, sulfites or organic (e.g., dietary amino acids and host mucins origin. The most extensively studied of the microbes involved in colonic sulfur metabolism are the sulfate-reducing bacteria, which are common colonic inhabitants. Many other microbial pathways are likely to shape colonic sulfur metabolism as well as the composition and availability of sulfated compounds, and these interactions need to be examined in more detail. Hydrogen sulfide is the sulfur derivative that has attracted the most attention in the context of colonic health, and the extent to which it is detrimental or beneficial remains in debate. Several lines of evidence point to sulfate-reducing bacteria or exogenous hydrogen sulfide as potential players in the etiology of intestinal disorders, inflammatory bowel diseases and colorectal cancer in particular. Generation of hydrogen sulfide via pathways other than dissimilatory sulfate reduction may be as, or more, important than those involving the sulfate-reducing bacteria. We suggest here that a novel axis of research is to assess the effects of hydrogen sulfide in shaping colonic microbiome structure. Clearly, in-depth characterization of the microbial pathways involved in colonic sulfur metabolism is necessary for a better understanding of its contribution to colonic disorders and development of therapeutic strategies.

Nano-Calorimetry based point of care biosensor for metabolic disease management.

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Kazura, Evan; Lubbers, Brad R; Dawson, Elliott; Phillips, John A; Baudenbacher, Franz

2017-09-01

Point of care (POC) diagnostics represents one of the fastest growing health care technology segments. Developments in microfabrication have led to the development of highly-sensitive nanocalorimeters ideal for directly measuring heat generated in POC biosensors. Here we present a novel nano-calorimeter-based biosensor design with differential sensing to eliminate common mode noise and capillary microfluidic channels for sample delivery to the thermoelectric sensor. The calorimeter has a resolution of 1.4 ± 0.2 nJ/(Hz) 1/2 utilizing a 27 junction bismuth/titanium thermopile, with a total Seebeck coefficient of 2160 μV/K. Sample is wicked to the calorimeter through a capillary channel making it suitable for monitoring blood obtained through a finger prick (performance in a model assay using catalase, achieving a threshold for hydrogen peroxide quantification of 50 μM. The potential for our device as a POC blood test for metabolic diseases is shown through the quantification of phenylalanine (Phe) in serum, an unmet necessary service in the management of Phenylketonuria (PKU). Pegylated phenylalanine ammonia-lyase (PEG-PAL) was utilized to react with Phe, but reliable detection was limited to <5 mM due to low enzymatic activity. The POC biosensor concept can be multiplexed and adapted to a large number of metabolic diseases utilizing different immobilized enzymes.

Cardiometabolic disease risk in metabolically healthy and unhealthy obesity: Stability of metabolic health status in adults.

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Guo, Fangjian; Garvey, W Timothy

2016-02-01

To assess the stability of metabolic status and body mass index (BMI) status and their relative contribution to risk of diabetes, cardiovascular events, and mortality. A total of 14,685 participants from the Atherosclerosis Risk in Communities Study and 4,990 from the Coronary Artery Risk Development in Young Adults Study were included. People with healthy obesity (HO) are defined as those meeting all three indices of blood pressure, blood glucose, and blood lipids. People with unhealthy obesity crossed the risk threshold for all three criteria. In both healthy and unhealthy subgroups, risks for coronary heart disease (CHD), stroke, and mortality were comparable among BMI status during a mean 18.7-year follow-up. When compared with HO, hazard ratios were increased for diabetes (5.56, 95% confidence interval [CI] 4.12-7.48), CHD (5.60, 95% CI 3.14-9.98), stroke (4.84, 95% CI 2.13-10.97), and mortality (2.6, 95% CI 1.88-3.61) in people with unhealthy obesity. BMI only moderately increased the risks for diabetes among healthy subjects. In the Coronary Artery Risk Development in Young Adults Study over 20 years, 17.5% of lean subjects and 67.3% of overweight subjects at baseline developed obesity during follow-up. Despite rising BMI, metabolic status remained relatively stable. Metabolic status is relatively stable despite rising BMI. HO had lower risks for diabetes, CHD, stroke, and mortality than unhealthy subjects but increased diabetes risks than healthy lean people. Cardiometabolic risk factors confer much higher risk than obesity per se. © 2015 The Obesity Society.

Endocrine Disrupting Chemical Induced "Pollution of Metabolic Pathways": A Case of Shifting Paradigms With Implications for Vascular Diseases.

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Janardhanan, Rajiv

2018-05-14

The latter half of the twentieth century has witnessed a humongous spurt in the use of synthetic chemicals in a wide variety of industrial and agricultural applications are leading to niche specific perturbations affecting every trophic level of the ecosystems due to unmitigated environmental contamination. Despite the incremental usefulness of endocrine disrupting chemicals (EDCs) such as pesticides and plasticizers, their statutory impact on environmental health is assuming worrisome proportions. The EDCs can disrupt physiological homeostasis resulting in developmental and reproductive abnormalities. Both preclinical animal experiments, as well as epidemiological studies, have correlated EDC exposure with metabolic disorders such as metabolic syndrome, type 2 diabetes as well as cardiovascular health. Here we briefly review the statutory impact of EDCs on metabolic disruption as well as their impact on environmental health. Finally, difficulties pertaining to the categorization of EDC induced metabolic diseases as risk factors for global disease burden have been addressed taking into account the complexity of such interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Inherent lipid metabolic dysfunction in glycogen storage disease IIIa.

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Li, Xin-Hua; Gong, Qi-Ming; Ling, Yun; Huang, Chong; Yu, De-Min; Gu, Lei-Lei; Liao, Xiang-Wei; Zhang, Dong-Hua; Hu, Xi-Qi; Han, Yue; Kong, Xiao-Fei; Zhang, Xin-Xin

2014-12-05

We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C > T (p.Gln40X) and c.753_756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.

Neuronal and astrocytic metabolism in a transgenic rat model of Alzheimer's disease.

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Nilsen, Linn Hege; Witter, Menno P; Sonnewald, Ursula

2014-05-01

Regional hypometabolism of glucose in the brain is a hallmark of Alzheimer's disease (AD). However, little is known about the specific alterations of neuronal and astrocytic metabolism involved in homeostasis of glutamate and GABA in AD. Here, we investigated the effects of amyloid β (Aβ) pathology on neuronal and astrocytic metabolism and glial-neuronal interactions in amino acid neurotransmitter homeostasis in the transgenic McGill-R-Thy1-APP rat model of AD compared with healthy controls at age 15 months. Rats were injected with [1-(13)C]glucose and [1,2-(13)C]acetate, and extracts of the hippocampal formation as well as several cortical regions were analyzed using (1)H- and (13)C nuclear magnetic resonance spectroscopy and high-performance liquid chromatography. Reduced tricarboxylic acid cycle turnover was evident for glutamatergic and GABAergic neurons in hippocampal formation and frontal cortex, and for astrocytes in frontal cortex. Pyruvate carboxylation, which is necessary for de novo synthesis of amino acids, was decreased and affected the level of glutamine in hippocampal formation and those of glutamate, glutamine, GABA, and aspartate in the retrosplenial/cingulate cortex. Metabolic alterations were also detected in the entorhinal cortex. Overall, perturbations in energy- and neurotransmitter homeostasis, mitochondrial astrocytic and neuronal metabolism, and aspects of the glutamate-glutamine cycle were found in McGill-R-Thy1-APP rats.

Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease

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Yii Michael

2011-09-01

Full Text Available Abstract Background Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE in men with coronary artery disease. Methods We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. Results All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E', consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red, or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyllysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. Conclusions Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the

Metabolic syndrome and menopause

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Jouyandeh Zahra

2013-01-01

Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

Measuring Glial Metabolism in Repetitive Brain Trauma and Alzheimer’s Disease

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2016-09-01

stages of repetitive brain trauma as well. Current methods of measure brain glutamate using proton spectroscopy is not specific to different cell...covering a representative range of clinical cases: a young female , young male , middle-aged male (all healthy volunteers) and a male patient with...AWARD NUMBER: W81XWH-15-1-0412 TITLE: Measuring Glial Metabolism in Repetitive Brain Trauma and Alzheimer’s Disease PRINCIPAL INVESTIGATOR

Fatty liver associated with metabolic derangement in patients with chronic kidney disease: A controlled attenuation parameter study

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Chang-Yun Yoon

2017-03-01

Full Text Available Background: Hepatic steatosis measured with controlled attenuation parameter (CAP using transient elastography predicts metabolic syndrome in the general population. We investigated whether CAP predicted metabolic syndrome in chronic kidney disease patients. Methods: CAP was measured with transient elastography in 465 predialysis chronic kidney disease patients (mean age, 57.5 years. Results: The median CAP value was 239 (202–274 dB/m. In 195 (41.9% patients with metabolic syndrome, diabetes mellitus was more prevalent (105 [53.8%] vs. 71 [26.3%], P < 0.001, with significantly increased urine albumin-to-creatinine ratio (184 [38–706] vs. 56 [16–408] mg/g Cr, P = 0.003, high sensitivity C-reactive protein levels (5.4 [1.4–28.2] vs. 1.7 [0.6–9.9] mg/L, P < 0.001, and CAP (248 [210–302] vs. 226 [196–259] dB/m, P < 0.001. In multiple linear regression analysis, CAP was independently related to body mass index (β = 0.742, P < 0.001, triglyceride levels (β = 2.034, P < 0.001, estimated glomerular filtration rate (β = 0.316, P = 0.001, serum albumin (β = 1.386, P < 0.001, alanine aminotransferase (β = 0.064, P = 0.029, and total bilirubin (β = −0.881, P = 0.009. In multiple logistic regression analysis, increased CAP was independently associated with increased metabolic syndrome risk (per 10 dB/m increase; odds ratio, 1.093; 95% confidence interval, 1.009–1.183; P = 0.029 even after adjusting for multiple confounding factors. Conclusion: Increased CAP measured with transient elastography significantly correlated with and could predict increased metabolic syndrome risk in chronic kidney disease patients.

Pathophysiology and molecular basis of selected metabolic abnormalities in Huntington’s disease

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Jolanta Krzysztoń-Russjan

2016-12-01

Full Text Available Huntington’s disease (HD is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed. HD symptoms include neurological disturbances, such as choreal movements with dystonia, speech and swallowing impairments, and additionally a variety of psychiatric and behavioral symptoms with cognitive decline have been described.They are the result of disturbances of several cellular pathways related to signal transmission, mitochondrial dysfunction and energy metabolism impairment shown by gene and protein expression and alteration of their functions. Impairment of energy processes demonstrated by a decrease of ATP production and increase of oxidative stress markers was determined in- and outside of the CNS in glycolysis, the Krebs cycle and the electron transport chain. A correlation between the increase of energy metabolism impairment level and the increase in number of CAG repeats in HTT has often been described. The energy metabolism study is an initial stage of sensitive biomarkers and a new therapeutic investigative option for early application in order to inhibit pathological processes in HD.Identification of pathological changes outside the CNS requires a reevaluation of diagnostic and therapeutic rules in HD.

Distinct brain metabolic patterns separately associated with cognition, motor function, and aging in Parkinson's disease dementia.

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Ko, Ji Hyun; Katako, Audrey; Aljuaid, Maram; Goertzen, Andrew L; Borys, Andrew; Hobson, Douglas E; Kim, Seok Min; Lee, Chong Sik

2017-12-01

We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [ 18 F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

Regional differences of relationships between atrophy and glucose metabolism of cerebral cortex in patients with Alzheimer's disease

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Toyama, H.; Uemura, K.; Kanekiyo, S.; Ishii, K.; Ishii, K.

2002-01-01

Aim: The purpose of this paper is to estimate a correlation between the extent of atrophy and the decline in the brain function measured with PET study among the patients with Alzheimer's disease by each brain lobe. Materials and Methods: Two groups, the normal controls (male: 8, female: 22 age: 62.4±4.9) and the patients with Alzheimer's disease (male: 6, female: 24, age: 65.9±7.2) participated in this study. The extent of atrophy was evaluated from the extracted gyrus on 2D-projection magnetic resonance imaging (MRI) and the cerebral cortical glucose metabolism was assessed on 2D-projection positron emission tomography (PET) image, and then a relationship between the cerebral atrophy and the function was evaluated by each brain lobe extracted automatically. 2D-projection of PET and MR images were made by means of the Mollweide method which keeps the area of the brain surface. In order to extract brain lobes from each subject automatically, the bitmap with different value by each brain lobe was made from a standard brain image and was automatically transformed to match each subject's brain image by using SPM99. A correlation image was generated between 2D-projection images of glucose metabolism and the area of the sulcus and the gyrus extracted from the correlation between MR and PET images clustered by K-means method. Results: The glucose metabolism of Alzheimer's disease was lower than that of normal control subjects at the frontal, parietal, and temporal lobes with the same extent of atrophy as that of the normal. There was high correlation between the area of gyrus and the glucose metabolism, and the correlation tendency of the Alzheimer's disease was steeper than that of the normal control at the parietal lobe. Conclusions: Combined analysis of regional morphology and function may be useful to distinguish pathological process such as early stage of Alzheimer's disease from normal physiological aging

Changes in Body Compositions and Basal Metabolic Rates during Treatment of Graves’ Disease

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Min Joo Kim

2018-01-01

Full Text Available Objectives. Because thyroid hormone is an important determinant of body weight and basal metabolic rate, we investigated the changes in the basal metabolic rate and body composition sequentially after treatment for Graves’ disease. Methods. A prospective cohort study was performed with six women newly diagnosed with Graves’ disease. During a 52-week treatment of methimazole, body composition, resting respiratory expenditure (REE, and handgrip strength were measured consecutively. Results. After methimazole treatment, body weight was initially increased (0–8 weeks, subsequently plateaued (8–24 weeks, and gradually decreased in the later period (24–52 weeks despite the decreased food intake. The measured REE was 40% higher than the predicted REE at baseline, and it gradually decreased after treatment. REE positively correlated with thyroid hormone levels, peripheral deiodinase activity, and thyroid’s secretory capacity. Body compositional analyses showed that the fat mass increased during an earlier period (4–12 weeks, while the lean mass increased significantly during the later period (26–52 weeks. Consistent with the lean mass changes, muscle strength also significantly increased during the later period. Conclusions. Treatment of Graves’ disease increased body weight and fat mass transiently with decreased REE. However, long-term compositional changes moved in a beneficial direction increasing lean mass and reinforcing muscle strength, following decreasing fat percentages.

Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

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Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

2014-01-01

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

Metabolic Syndrome in Chemical Warfare Patients with Chronic Obstructive Pulmonary Disease

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Shahrzad M. Lari

2014-11-01

Full Text Available   Introduction: Sulfur mustard (SM, a toxic alkylating gas, can cause serious long-term pulmonary complications such as chronic obstructive pulmonary disease (COPD. Metabolic syndrome (MetS is one of the important comorbidities of COPD. This study was designed to evaluate the frequency of metabolic syndrome in Iranian chemical warfare patients (CWPs with COPD. Materials and Methods: Thirty CWPs with a mean age of 46.93± 6.8 were enrolled in this study. The following parameters were studied in: complete pulmonary function tests, health-related quality of life, serum triglycerides (TG, high density lipoprotein (HDL and fasting blood sugar (FBS levels. Additionally, 32 COPD patients and 56 healthy persons were considered as control groups who were matched to CWPs. Results: We found a statistically significant difference in the frequency of MetS between the COPD patients and the healthy control group (p=0.04. Additionally, we observed a statistically significant difference in the mean HDL levels among these groups (p=

Insulin Signaling, Resistance, and the Metabolic Syndrome: Insights from Mouse Models to Disease Mechanisms

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Guo, Shaodong

2014-01-01

Insulin resistance is a major underlying mechanism for the “metabolic syndrome”, which is also known as insulin resistance syndrome. Metabolic syndrome is increasing at an alarming rate, becoming a major public and clinical problem worldwide. Metabolic syndrome is represented by a group of interrelated disorders, including obesity, hyperglycemia, hyperlipidemia, and hypertension. It is also a significant risk factor for cardiovascular disease and increased morbidity and mortality. Animal studies demonstrate that insulin and its signaling cascade normally control cell growth, metabolism and survival through activation of mitogen-activated protein kinases (MAPKs) and phosphotidylinositide-3-kinase (PI3K), of which activation of PI-3K-associated with insulin receptor substrate-1 and -2 (IRS1, 2) and subsequent Akt→Foxo1 phosphorylation cascade has a central role in control of nutrient homeostasis and organ survival. Inactivation of Akt and activation of Foxo1, through suppression IRS1 and IRS2 in different organs following hyperinsulinemia, metabolic inflammation, and over nutrition may provide the underlying mechanisms for metabolic syndrome in humans. Targeting the IRS→Akt→Foxo1 signaling cascade will likely provide a strategy for therapeutic intervention in the treatment of type 2 diabetes and its complications. This review discusses the basis of insulin signaling, insulin resistance in different mouse models, and how a deficiency of insulin signaling components in different organs contributes to the feature of the metabolic syndrome. Emphasis will be placed on the role of IRS1, IRS2, and associated signaling pathways that couple to Akt and the forkhead/winged helix transcription factor Foxo1. PMID:24281010

The current state of GPCR-based drug discovery to treat metabolic disease.

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Sloop, Kyle W; Emmerson, Paul J; Statnick, Michael A; Willard, Francis S

2018-02-02

One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour. © 2018 The British Pharmacological Society.

Role of metabolic overload and metabolic inflammation in the development of Nonalcoholic Steatohepatitis (NASH)

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Liang, W.

2015-01-01

Overload of nutrients can lead to diet-induced inflammation, also called metabolic inflammation, which is thought to play an important role in many metabolic diseases, including the development of nonalcoholic fatty liver disease (NAFLD). NAFLD encompasses a spectrum of pathologies that range from

Hypogonadism in testicular cancer patients is associated with risk factors of cardiovascular disease and the metabolic syndrome.

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Bogefors, C; Isaksson, S; Bobjer, J; Kitlinski, M; Leijonhufvud, I; Link, K; Giwercman, A

2017-07-01

More than 95% of testicular cancer are cured but they are at increased long-term risk of cardiovascular disease. The risk of cardiovascular disease and treatment intensity was reported, but it is unknown whether this effect of cancer therapy is direct or indirect, mediated through androgen deficiency. Our aim was, therefore, to evaluate whether testicular cancer patients have increased the prevalence of risk factors of cardiovascular disease and if these risk factors are associated with hypogonadism and/or the cancer treatment given. In 92 testicular cancer patients (mean 9.2 years follow-up) and age-matched controls, blood samples were analysed for lipids, total testosterone, luteinizing hormone (LH), glucose and insulin. An estimate of insulin resistance, HOMAir was calculated. Hypogonadism was defined as total testosterone  10 IU/L and/or androgen replacement. In testicular cancer men with hypogonadism, compared with eugonadal patients, higher insulin (mean difference: 3.10 mIU/L; p = 0.002) and HOMAir (mean difference: 0.792; p = 0.007) were detected. Hypogonadism group presented with increased risk (OR = 4.4; p = 0.01) of metabolic syndrome. Most associations between the treatment given and the metabolic parameters became statistically non-significant after adjustment for hypogonadism. In conclusion, testicular cancer patients with signs of hypogonadism presented with significantly increased risk of metabolic syndrome and investigation of endocrine and metabolic parameters is warranted in these patients. © 2017 American Society of Andrology and European Academy of Andrology.

The metabolic role of the gut microbiota in health and rheumatic disease: mechanisms and interventions.

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Abdollahi-Roodsaz, Shahla; Abramson, Steven B; Scher, Jose U

2016-08-01

The role of the gut microbiome in animal models of inflammatory and autoimmune disease is now well established. The human gut microbiome is currently being studied as a potential modulator of the immune response in rheumatic disorders. However, the vastness and complexity of this host-microorganism interaction is likely to go well beyond taxonomic, correlative observations. In fact, most advances in the field relate to the functional and metabolic capabilities of these microorganisms and their influence on mucosal immunity and systemic inflammation. An intricate relationship between the microbiome and the diet of the host is now fully recognized, with the microbiota having an important role in the degradation of polysaccharides into active metabolites. This Review summarizes the current knowledge on the metabolic role of the microbiota in health and rheumatic disease, including the advances in pharmacomicrobiomics and its potential use in diagnostics, therapeutics and personalized medicine.

[Menopause and metabolic syndrome].

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Meirelles, Ricardo M R

2014-03-01

The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

Bile Acid Signaling in Liver Metabolism and Diseases

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Tiangang Li

2012-01-01

Full Text Available Obesity, diabetes, and metabolic syndromes are increasingly recognized as health concerns worldwide. Overnutrition and insulin resistance are the major causes of diabetic hyperglycemia and hyperlipidemia in humans. Studies in the past decade provide evidence that bile acids are not just biological detergents facilitating gut nutrient absorption, but also important metabolic regulators of glucose and lipid homeostasis. Pharmacological alteration of bile acid metabolism or bile acid signaling pathways such as using bile acid receptor agonists or bile acid binding resins may be a promising therapeutic strategy for the treatment of obesity and diabetes. On the other hand, bile acid signaling is complex, and the molecular mechanisms mediating the bile acid effects are still not completely understood. This paper will summarize recent advances in our understanding of bile acid signaling in regulation of glucose and lipid metabolism, and the potentials of developing novel therapeutic strategies that target bile acid metabolism for the treatment of metabolic disorders.

The Impact of Dietary and Metabolic Risk Factors on Cardiovascular Diseases and Type 2 Diabetes Mortality in Brazil

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de Oliveira Otto, Marcia C.; Afshin, Ashkan; Micha, Renata; Khatibzadeh, Shahab; Fahimi, Saman; Singh, Gitanjali; Danaei, Goodarz; Sichieri, Rosely; Monteiro, Carlos A; Louzada, Maria L. C.; Ezzati, Majid; Mozaffarian, Dariush

2016-01-01

Background Trends in food availability and metabolic risk factors in Brazil suggest a shift toward unhealthy dietary patterns and increased cardiometabolic disease risk, yet little is known about the impact of dietary and metabolic risk factors on cardiometabolic mortality in Brazil. Methods Based on data from Global Burden of Disease (GBD) Study, we used comparative risk assessment to estimate the burden of 11 dietary and 4 metabolic risk factors on mortality due to cardiovascular diseases and diabetes in Brazil in 2010. Information on national diets and metabolic risks were obtained from the Brazilian Household Budget Survey, the Food and Agriculture Organization database, and large observational studies including Brazilian adults. Relative risks for each risk factor were obtained from meta-analyses of randomized trials or prospective cohort studies; and disease-specific mortality from the GBD 2010 database. We quantified uncertainty using probabilistic simulation analyses, incorporating uncertainty in dietary and metabolic data and relative risks by age and sex. Robustness of findings was evaluated by sensitivity to varying feasible optimal levels of each risk factor. Results In 2010, high systolic blood pressure (SBP) and suboptimal diet were the largest contributors to cardiometabolic deaths in Brazil, responsible for 214,263 deaths (95% uncertainty interval [UI]: 195,073 to 233,936) and 202,949 deaths (95% UI: 194,322 to 211,747), respectively. Among individual dietary factors, low intakes of fruits and whole grains and high intakes of sodium were the largest contributors to cardiometabolic deaths. For premature cardiometabolic deaths (before age 70 years, representing 40% of cardiometabolic deaths), the leading risk factors were suboptimal diet (104,169 deaths; 95% UI: 99,964 to 108,002), high SBP (98,923 deaths; 95%UI: 92,912 to 104,609) and high body-mass index (BMI) (42,643 deaths; 95%UI: 40,161 to 45,111). Conclusion suboptimal diet, high SBP, and high

Enhanced thyroid iodine metabolism in patients with triiodothyronine-predominant Graves' disease

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Takamatsu, J.; Hosoya, T.; Naito, N.

1988-01-01

Some patients with hyperthyroid Graves' disease have increased serum T3 and normal or even low serum T4 levels during treatment with antithyroid drugs. These patients with elevated serum T3 to T4 ratios rarely have a remission of their hyperthyroidism. The aim of this study was to investigate thyroid iodine metabolism in such patients, whom we termed T3-predominant Graves' disease. Mean thyroid radioactive iodine uptake was 51.0 +/- 18.1% ( +/- SD) at 3 h, and it decreased to 38.9 +/- 20.1% at 24 h in 31 patients with T3-predominant Graves' disease during treatment. It was 20.0 +/- 11.4% at 3 h and increased to 31.9 +/- 16.0% at 24 h in 17 other patients with hyperthyroid Graves' disease who had normal serum T3 and T4 levels and a normal serum T3 to T4 ratio during treatment (control Graves' disease). The activity of serum TSH receptor antibodies was significantly higher in the patients with T3-predominant Graves' disease than in control Graves' disease patients. From in vitro studies of thyroid tissue obtained at surgery, both thyroglobulin content and iodine content in thyroglobulin were significantly lower in patients with T3-predominant Graves' disease than in the control Graves' disease patients. Thyroid peroxidase (TPO) activity determined by a guaiacol assay was 0.411 +/- 0.212 g.u./mg protein in the T3-predominant Graves' disease patients, significantly higher than that in the control Graves' disease patients. Serum TPO autoantibody levels determined by immunoprecipitation also were greater in T3-predominant Graves' disease patients than in control Graves' disease patients. Binding of this antibody to TPO slightly inhibited the enzyme activity of TPO, but this effect of the antibody was similar in the two groups of patients

Chylomicrons metabolism in patients with coronary artery disease; Metabolismo de quilomicrons em pacientes portadores de doenca arterial coronaria

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Brandizzi, Laura Ines Ventura

2002-07-01

Chylomicrons are the triglyceride-rich lipoproteins that carry dietary lipids absorbed in the intestine. In the bloodstream , chylomicron triglycerides are broken-down by lipoprotein lipase using apoliprotein (apo) CII as co factor. Fatty acids and glycerol resulting from the enzymatic action are absorbed and stored in the body tissues mainly adipose and muscle for subsequent utilizations energy source. The resulting triglycerides depleted remnants are taken-up by liver receptor such as the LDL receptor using mainly apo E as ligand. For methodological reasons, chylomicron metabolism has been unfrequently studied in subjects despite its pathophysiological importance, and this metabolism was not evaluated in the great clinical trials that established the link between atherosclerosis and lipids. In studies using oral fat load tests, it has been shown that in patients with coronary artery disease there is a trend to accumulation of post-prandial triglycerides, vitamin A or apo B-48 , suggesting that in those patients chylomicrons and their remnants are slowly removed from the circulation. A triglyceride-rich emulsion marked radioisotopic which mimics chylomicron metabolism when injected into the bloodstream has been described that can offer a more straight forward approach to evaluate chylomicrons. In coronary artery disease patients both lipolysis and remnant removal from the plasma of the chylomicron-like emulsions were found slowed-down compared with control subjects without the disease. The introduction of more practical techniques to assess chylomicron metabolism may be new mechanisms underlying atherogenesis. (author)

Metabolic Myopathies.

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Tarnopolsky, Mark A

2016-12-01

Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

An Overview of Novel Dietary Supplements and Food Ingredients in Patients with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease

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Priscila Silva Figueiredo

2018-04-01

Full Text Available Metabolic syndrome (MetS is characterized by interconnected factors related to metabolic disturbances, and is directly related to the occurrence of some diseases such as cardiovascular diseases and type 2 diabetes. MetS is described as one or both of insulin resistance and visceral adiposity, considered the initial causes of abnormalities that include hyperglycemia, elevated blood pressure, dyslipidemia, elevated inflammatory markers, and prothrombotic state, as well as polycystic ovarian syndrome in women. Other than in MetS, visceral adiposity and the pro-inflammatory state are also key in the development of non-alcoholic fatty liver disease (NAFLD, which is the most prevalent chronic liver disease in modern society. Both MetS and NAFLD are related to diet and lifestyle, and their treatment may be influenced by dietary pattern changes and the use of certain dietary supplements. This study aimed to review the role of food ingredients and supplements in the management of MetS and NAFLD specifically in human clinical trials. Moreover, bioactive compounds and polyunsaturated fatty acids (PUFAs may be used as strategies for preventing the onset of and treatment of metabolic disorders, such as MetS and NAFLD, improving the inflammatory state and other comorbidities, such as obesity, dyslipidemias, and cardiovascular diseases (CVD.

The gut microbiota and metabolic disease: current understanding and future perspectives.

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Arora, T; Bäckhed, F

2016-10-01

The human gut microbiota has been studied for more than a century. However, of nonculture-based techniques exploiting next-generation sequencing for analysing the microbiota, development has renewed research within the field during the past decade. The observation that the gut microbiota, as an environmental factor, contributes to adiposity has further increased interest in the field. The human microbiota is affected by the diet, and macronutrients serve as substrates for many microbially produced metabolites, such as short-chain fatty acids and bile acids, that may modulate host metabolism. Obesity predisposes towards type 2 diabetes and cardiovascular disease. Recently, it has been established that levels of butyrate-producing bacteria are reduced in patients with type 2 diabetes, whereas levels of Lactobacillus sp. are increased. Recent data suggest that the reduced levels of butyrate-producing bacteria might be causally linked to type 2 diabetes. Bariatric surgery, which promotes long-term weight loss and diabetes remission, alters the gut microbiota in both mice and humans. Furthermore, by transferring the microbiota from postbariatric surgery patients to mice, it has been demonstrated that an altered microbiota may contribute to the improved metabolic phenotype following this intervention. Thus, greater understanding of alterations of the gut microbiota, in combination with dietary patterns, may provide insights into how the gut microbiota contributes to disease progression and whether it can be exploited as a novel diagnostic, prognostic and therapeutic target. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Innovative dairy cow management to improve resistance to metabolic and infectious diseases during the transition period.

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Lacasse, P; Vanacker, N; Ollier, S; Ster, C

2018-02-01

The incidence of metabolic and infectious diseases varies greatly during the lactation cycle. Most new cases of clinical mastitis appear at the beginning of lactation, and the incidence increases with the level of milk production. In addition to mastitis, many other infectious diseases become clinically apparent during the first 2weeks of lactation. During this time, cows are in a negative energy balance and must mobilize body reserves to balance the deficit between food energy intake and energy required for milk production. The relationships between energy deficit and metabolic diseases, such as ketosis and hepatic lipidosis, are well known. Furthermore, cows in energy deficit have a weakened immune system and are therefore more susceptible to infections. There is now good evidence that the increase in circulating non-esterified fatty acids impairs immune cell functions. Therefore, management approaches that reduce the negative energy balance and the increase in non-esterified fatty acids at the beginning of lactation are likely to improve resistance to infection. Improving the nutrient supply through periparturient nutritional management has been the subject of considerable research. However, another way to reduce the imbalance between nutrient supply and demand is to temporarily decrease the latter. In this review, we examine how management strategies such as conjugated linoleic acid feeding, prepartum milking, or limiting postpartum milk production could be used to reduce metabolic perturbations and immunosuppression during the transition period. At this stage, it appears that reducing the amount of milk harvested postpartum by means of partial milking in the first days after calving is the most promising approach to reduce metabolic stress and immunosuppression without compromising the productivity of high-yielding dairy cows. Copyright © 2017. Published by Elsevier Ltd.

MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation

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Jan, Wajanat; Wang, Zhiyue J. [Department of Radiology, University of Pennsylvania School of Medicine, Children' s Hospital of Philadelphia, Pennsylvania (United States); Zimmerman, Robert A. [Department of Radiology, University of Pennsylvania School of Medicine, Children' s Hospital of Philadelphia, Pennsylvania (United States); Department of Radiology, Children' s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, Philadelphia (United States); Berry, Gerard T.; Kaplan, Paige B.; Kaye, Edward M. [Department of Pediatrics, University of Pennsylvania School of Medicine, The Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States)

2003-06-01

Maple syrup urine disease (MSUD) is an inborn error of amino acid metabolism, which affects the brain tissue resulting in impairment or death if untreated. Imaging studies have shown reversible brain edema during acute metabolic decompensation. The purpose of this paper is to describe the diffusion-weighted imaging (DWI) and spectroscopy findings during metabolic decompensation and to assess the value of these findings in the prediction of patient outcome. Six patients with the diagnosis of MSUD underwent conventional MR imaging with DWI during acute presentation with metabolic decompensation. Spectroscopy with long TE was performed in four of the six patients. Follow-up examinations were performed after clinical and metabolic recovery. DWI demonstrated marked restriction of proton diffusion compatible with cytotoxic or intramyelinic sheath edema in the brainstem, basal ganglia, thalami, cerebellar and periventricular white matter and the cerebral cortex. This was accompanied by the presence of an abnormal branched-chain amino acids (BCAA) and branched-chain alpha-keto acids (BCKA) peak at 0.9 ppm as well as elevated lactate on proton spectroscopy in all four patients. The changes in all six patients were reversed with treatment without evidence of volume loss or persistent tissue damage. The presence of cytotoxic or intramyelinic edema as evidenced by restricted water diffusion on DWI, with the presence of lactate on spectroscopy, could imply imminent cell death. However, in the context of metabolic decompensation in MSUD, it appears that changes in cell osmolarity and metabolism can reverse completely after metabolic correction. (orig.)

MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation

International Nuclear Information System (INIS)

Jan, Wajanat; Wang, Zhiyue J.; Zimmerman, Robert A.; Berry, Gerard T.; Kaplan, Paige B.; Kaye, Edward M.

2003-01-01

Maple syrup urine disease (MSUD) is an inborn error of amino acid metabolism, which affects the brain tissue resulting in impairment or death if untreated. Imaging studies have shown reversible brain edema during acute metabolic decompensation. The purpose of this paper is to describe the diffusion-weighted imaging (DWI) and spectroscopy findings during metabolic decompensation and to assess the value of these findings in the prediction of patient outcome. Six patients with the diagnosis of MSUD underwent conventional MR imaging with DWI during acute presentation with metabolic decompensation. Spectroscopy with long TE was performed in four of the six patients. Follow-up examinations were performed after clinical and metabolic recovery. DWI demonstrated marked restriction of proton diffusion compatible with cytotoxic or intramyelinic sheath edema in the brainstem, basal ganglia, thalami, cerebellar and periventricular white matter and the cerebral cortex. This was accompanied by the presence of an abnormal branched-chain amino acids (BCAA) and branched-chain alpha-keto acids (BCKA) peak at 0.9 ppm as well as elevated lactate on proton spectroscopy in all four patients. The changes in all six patients were reversed with treatment without evidence of volume loss or persistent tissue damage. The presence of cytotoxic or intramyelinic edema as evidenced by restricted water diffusion on DWI, with the presence of lactate on spectroscopy, could imply imminent cell death. However, in the context of metabolic decompensation in MSUD, it appears that changes in cell osmolarity and metabolism can reverse completely after metabolic correction. (orig.)

Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.

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Lesley Jones

2010-11-01

Full Text Available Late Onset Alzheimer's disease (LOAD is the leading cause of dementia. Recent large genome-wide association studies (GWAS identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.

Maternal cardiac metabolism in pregnancy

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Liu, Laura X.; Arany, Zolt

2014-01-01

Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

Metabolic interrelationships software application: Interactive learning tool for intermediary metabolism

NARCIS (Netherlands)

A.J.M. Verhoeven (Adrie); M. Doets (Mathijs); J.M.J. Lamers (Jos); J.F. Koster (Johan)

2005-01-01

textabstractWe developed and implemented the software application titled Metabolic Interrelationships as a self-learning and -teaching tool for intermediary metabolism. It is used by undergraduate medical students in an integrated organ systems-based and disease-oriented core curriculum, which

Nor-Ursodeoxycholic Acid as a Novel Therapeutic Approach for Cholestatic and Metabolic Liver Diseases.

Science.gov (United States)

Halilbasic, Emina; Steinacher, Daniel; Trauner, Michael

2017-01-01

Norursodeoxycholic acid (norUDCA) is a side-chain-shortened derivative of ursodeoxycholic acid with relative resistance to amidation, which enables its cholehepatic shunting. Based on its specific pharmacologic properties, norUDCA is a promising drug for a range of cholestatic liver and bile duct disorders. Recently, norUDCA has been successfully tested clinically in patients with primary sclerosing cholangitis (PSC) as first application in patients. Moreover, hepatic enrichment of norUDCA facilitates direct therapeutic effects on both parenchymal and non-parenchymal liver cells, thereby counteracting cholestasis, steatosis, hepatic inflammation and fibrosis, inhibiting hepatocellular proliferation, and promoting autophagy. This may open its therapeutic use to other non-cholestatic and metabolic liver diseases. This review article is a summary of a lecture given at the XXIV International Bile Acid Meeting (Falk Symposium 203) on "Bile Acids in Health and Disease" held in Düsseldorf, on June 17-18, 2016 and summarizes the recent progress of norUDCA as novel therapeutic approach in cholestatic and metabolic liver disorders with a specific focus on PSC. © 2017 S. Karger AG, Basel.

Gender Differences in Metabolic Disorders and Related Diseases in Spontaneously Diabetic Torii-Leprfa Rats

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Takeshi Ohta

2014-01-01

Full Text Available The Spontaneously Diabetic Torii Leprfa (SDT fatty rat is a novel type 2 diabetic model wherein both male and female rats develop glucose and lipid abnormalities from a young age. In this study, we investigated gender differences in abnormalities and related complications in SDT fatty rats. Food intake was higher in males compared to female rats; however, body weight was not different between genders. Progression of diabetes, including increases in blood glucose and declines in blood insulin, was observed earlier in male rats than in females, and diabetic grade was more critical in male rats. Blood lipids tended to increase in female rats. Gonadal dysfunction was observed in both male and female rats with aging. Microangiopathies, such as nephropathy, retinopathy, neuropathy, and osteoporosis, were seen in both genders, and pathological grade and progression were more significant in males. Qualitative and quantitative changes were observed for metabolic disease gender differences in SDT fatty rats. The SDT fatty rat is a useful model for researching gender differences in metabolic disorders and related diseases in diabetes with obesity.

Regional difference of glucose metabolism reduction in equivocal Alzheimer's disease and elderly depressed patients

International Nuclear Information System (INIS)

Cho, S. S.; Kang, E. J.; Lee, J. S.; Lee, D. S.; Lee, K. U.; Chung, J. K.; Woo, J. I.; Lee, M. C.

2001-01-01

The aim of this study was to investigate the difference in cerebral glucose metabolism between patients with equivocal Alzheimer's disease (eAD) and those with elderly major depression (DEP). 31 patients with eAD, 7 patients with DEP, and 15 age matched normal controls were scanned with FDG-PET. Each FDG-PET images was normalized to the cerebellar activity before voxel-voxel analysis using SPM99. In comparison with normal controls, the eAD patents showed the most significant reduction of glucose metabolism (hypometabolism) in anterior inferior temporal gyrus in left, followed by bilateral posterior cingulate, left thalamus, and inferior parietal lobe. Patients with DEP showed hypometabolism in precuneus, inferior and middle frontal gyri in left, and right angular gyrus. Significantly lower activity was found in left inferior temporal gyrus in DEP in comparison to the eAD. Patients with eAD and DEP showed different pattern of hypometabolism, especially in inferior temporal gyrus. FDG brain PET may be useful in differential diagnosis between equivocal Alzheimer's disease and elderly depression

Framingham risk score for estimation of 10-years of cardiovascular diseases risk in patients with metabolic syndrome.

Science.gov (United States)

Jahangiry, Leila; Farhangi, Mahdieh Abbasalizad; Rezaei, Fatemeh

2017-11-13

There are a few studies evaluating the predictive value of Framingham risk score (FRS) for cardiovascular disease (CVD) risk assessment in patients with metabolic syndrome in Iran. Because of the emerging high prevalence of CVD among Iranian population, it is important to predict its risk among populations with potential predictive tools. Therefore, the aim of the current study is to evaluate the FRS and its determinants in patients with metabolic syndrome. In the current cross-sectional study, 160 patients with metabolic syndrome diagnosed according to the National Cholesterol Education Adult Treatment Panel (ATP) III criteria were enrolled. The FRS was calculated using a computer program by a previously suggested algorithm. Totally, 77.5, 16.3, and 6.3% of patients with metabolic syndrome were at low, intermediate, and high risk of CVD according to FRS categorization. The highest prevalence of all of metabolic syndrome components were in low CVD risk according to the FRS grouping (P metabolic syndrome and different FRS categorization among patients with metabolic syndrome were identified. High SBP and FSG were associated with meaningfully increased risk of CVD compared with other parameters. The study is not a trial; the registration number is not applicable.

Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function

International Nuclear Information System (INIS)

Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.

1988-01-01

Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of 18 F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation

Brain metabolic changes in Hodgkin disease patients following diagnosis and during the disease course: An 18F-FDG PET/CT study.

Science.gov (United States)

Chiaravalloti, Agostino; Pagani, Marco; Cantonetti, Maria; DI Pietro, Barbara; Tavolozza, Mario; Travascio, Laura; DI Biagio, Daniele; Danieli, Roberta; Schillaci, Orazio

2015-02-01

The aim of the present study was to investigate brain glucose metabolism in patients with Hodgkin disease (HD) after diagnosis and during chemotherapy treatment. Following the administration of first-line doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy, 74 HD patients underwent 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography brain scans, both baseline (PET0) and interim (PET2) at the Department of Biomedicine and Prevention, University of Rome Tor Vergata (Rome, Italy). Fifty-seven patients were further evaluated 15±6 days after four additional cycles (PET6). Furthermore, a control group (CG) of 40 chemotherapy-naïve subjects was enrolled. Differences in brain 18 F-FDG uptake between the CG, PET0, PET2 and PET6 scans were analyzed using statistical parametric mapping. Compared with the PET0 and CG scans, the PET2 scan demonstrated a higher metabolic activity in Brodmann area (BA) 39, and a metabolic reduction in BA 11 bilaterally and in left BA 32. All of these changes disappeared at PET6. The results of the present study indicate that ABVD chemotherapy has a limited impact on brain metabolism.

Lafora disease offers a unique window into neuronal glycogen metabolism.

Science.gov (United States)

Gentry, Matthew S; Guinovart, Joan J; Minassian, Berge A; Roach, Peter J; Serratosa, Jose M

2018-05-11

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

International Nuclear Information System (INIS)

Rougemont, D.; Baron, J.C.; Collard, P.; Bustany, P.; Comar, D.; Agid, Y.

1983-06-01

Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and 18 F-Fluoro-2-deoxy-D-glucose ( 18 FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain

Metabolic disorders in menopause

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Grzegorz Stachowiak

2015-04-01

Full Text Available Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance – IGT, type 2 diabetes mellitus – T2DM or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women’s life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases in menopause, including the role of a tailored menopausal hormone therapy (HT. According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy. Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

Metabolic Syndrome and Outcomes after Renal Intervention

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Daynene Vykoukal

2011-01-01

Full Text Available Metabolic syndrome significantly increases the risk for cardiovascular disease and chronic kidney disease. The increased risk for cardiovascular diseases can partly be caused by a prothrombotic state that exists because of abdominal obesity. Multiple observational studies have consistently shown that increased body mass index as well as insulin resistance and increased fasting insulin levels is associated with chronic kidney disease, even after adjustment for related disorders. Metabolic syndrome appears to be a risk factor for chronic kidney disease, likely due to the combination of dysglycemia and high blood pressure. Metabolic syndrome is associated with markedly reduced renal clinical benefit and increased progression to hemodialysis following endovascular intervention for atherosclerotic renal artery stenosis. Metabolic syndrome is associated with inferior early outcomes for dialysis access procedures.

Effect of specific amino acids on hepatic lipid metabolism in fructose-induced non-alcoholic fatty liver disease.

Science.gov (United States)

Jegatheesan, Prasanthi; Beutheu, Stéphanie; Ventura, Gabrielle; Sarfati, Gilles; Nubret, Esther; Kapel, Nathalie; Waligora-Dupriet, Anne-Judith; Bergheim, Ina; Cynober, Luc; De-Bandt, Jean-Pascal

2016-02-01

Fructose diets have been shown to induce insulin resistance and to alter liver metabolism and gut barrier function, ultimately leading to non-alcoholic fatty liver disease. Citrulline, Glutamine and Arginine may improve insulin sensitivity and have beneficial effects on gut trophicity. Our aim was to evaluate their effects on liver and gut functions in a rat model of fructose-induced non-alcoholic fatty liver disease. Male Sprague-Dawley rats (n = 58) received a 4-week fructose (60%) diet or standard chow with or without Citrulline (0.15 g/d) or an isomolar amount of Arginine or Glutamine. All diets were made isonitrogenous by addition of non-essential amino acids. At week 4, nutritional and metabolic status (plasma glucose, insulin, cholesterol, triglycerides and amino acids, net intestinal absorption) was determined; steatosis (hepatic triglycerides content, histological examination) and hepatic function (plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin) were assessed; and gut barrier integrity (myeloperoxidase activity, portal endotoxemia, tight junction protein expression and localization) and intestinal and hepatic inflammation were evaluated. We also assessed diets effects on caecal microbiota. In these experimental isonitrogenous fructose diet conditions, fructose led to steatosis with dyslipidemia but without altering glucose homeostasis, liver function or gut permeability. Fructose significantly decreased Bifidobacterium and Lactobacillus and tended to increase endotoxemia. Arginine and Glutamine supplements were ineffective but Citrulline supplementation prevented hypertriglyceridemia and attenuated liver fat accumulation. While nitrogen supply alone can attenuate fructose-induced non-alcoholic fatty liver disease, Citrulline appears to act directly on hepatic lipid metabolism by partially preventing hypertriglyceridemia and steatosis. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition

[DYNAMIC OF CLINICAL, LABORATORY AND SONOGRAPHIC PARAMETERS AFTER SUCCESSFUL LITHOLITIC THERAPY AT PATIENTS WITH GALLSTONE DISEASE IN ASSOCIATION WITH METABOLIC SYNDROME].

Science.gov (United States)

Gaus, O V; Akhmedov, V A

2015-01-01

The aim of study was to determine the leading clinical, immunological and sonographic pararneters, reflecting the efficiency of Ursodeoxycholic acid (UDCA) at the rate of 10 mg per 1 kg of body weight in the treatment of gallstone disease in patients with metabolic syndrome (MS). An assessment of clinical, biochemical immunological and sonographic parameters in 54 patients with gallstone disease associated with the metabolic syndrome before and after the six-month treatment UDCA were made. In accordance with our results the significant predictors, reflecting successful litholitic therapy at patients with gallstone disease in association with metabolic syndrome are decrease the serum concentration of gamma-glutamyltranspeptidase (P = 0.003), matrix metalloproteinase-9 (P = 0.001), increase the serum concentration of tissue inhibitor of metalloproteinases-1 (P = 0.02), decrease the left liver lobe thickness (P = 0,003) and the thickness of gallbladder wall (P = 0.0002). The results of our study have shown that the therapy with ursodesoxycholic acid of patients with metabolic syndrome leads to decrease of factors of gallstone progression (elevated levels of gamma-glutamyltranspeptidase, matrix metalloproteinase-9 and increased thickness of the left lobe liver and gallbladder wall).

Impact of the Heart WATCH Program on Patients at Risk of Developing Metabolic Syndrome, Prediabetes or Cardiovascular Disease

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Jennifer Fink

2015-04-01

Full Text Available Purpose: Metabolic syndrome is a set of metabolic risk factors associated with increased risk of developing cardiovascular disease and type 2 diabetes mellitus. We retrospectively evaluated the effectiveness of a lifestyle modification program (Heart WATCH geared toward reducing development of chronic disease in women deemed at risk for metabolic syndrome, prediabetes and/or cardiovascular disease. Methods: Our institution’s Heart WATCH program consists of screening sessions with a multidisciplinary team (physician/nurse, nutritionist and psychologist, a minimum of three visits with a nurse practitioner and weekly follow-up phone calls for a 14-week period. Sociodemographic variables were obtained at initial visit. Biometric testing indices and self-reported clinical and behavioral health measures were recorded pre- and postintervention, and compared using paired t-tests or McNemar’s test as appropriate. Results: Heart WATCH enrolled 242 women from November 2006 to April 2014, and 193 (80% completed all phases of the 14-week lifestyle intervention. Postintervention, participants demonstrated improved health status in all areas and improved significantly in the following areas: diet/nutrition (P=0.014, exercise (P<0.001, stress (P<0.0001, quality of life (P=0.003, weight (P<0.0001, waist circumference (P=0.01 and total cholesterol (P=0.019. Clinically meaningful improvements were realized by participants who moved to a healthier classification in a number of vital signs and blood panel indices. Conclusions: These findings suggest the “elevated risk profile” for women with components of metabolic syndrome can be reversed through a lifestyle program focused on reducing risk factors associated with cardiovascular disease and prediabetes. Future research is needed to determine mechanisms of risk reduction as well as optimal patient-centered and culturally appropriate approaches to weight management.

Longitudinal brain metabolic changes from amnestic mild cognitive impairment to Alzheimer's disease

Science.gov (United States)

Fouquet, Marine; Desgranges, Béatrice; Landeau, Brigitte; Duchesnay, Edouard; Mézenge, Florence; De La Sayette, Vincent; Viader, Fausto; Baron, Jean-Claude; Eustache, Francis; Chételat, Gaël

2009-01-01

A sensitive marker for monitoring progression of early Alzheimer’s Disease (AD) would help to develop and test new therapeutic strategies. The present study aimed at investigating brain metabolism changes over time, as potential monitoring marker, in patients with amnestic Mild Cognitive Impairment (aMCI), according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen aMCI patients underwent MRI and 18FDG-PET scans both at inclusion and 18 months later. Baseline and follow-up PET data were corrected for partial volume effects and spatially normalized using MRI data, scaled to the vermis and compared using SPM2. ‘PET-PAC’ maps reflecting metabolic percent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than nonconverters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-PET for monitoring early AD progression. PMID:19477964

Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases.

Science.gov (United States)

Erdöl, Şahin; Sağlam, Halil

2016-09-01

Inherited metabolic diseases (IMDs) can affect many organ systems, including the endocrine system. There are limited data regarding endocrine dysfunctions related to IMDs in adults, however, no data exist in pediatric patients with IMDs. The aim of this study was to investigate endocrine dysfunctions in patients with IMDs by assessing their demographic, clinical, and laboratory data. Data were obtained retrospectively from the medical reports of patients with IMDs who were followed by the division of pediatric metabolism and nutrition between June 2011 and November 2013. In total, 260 patients [139 males (53%) and 121 females (47%)] with an IMD diagnosis were included in the study. The mean age of the patients was 5.94 (range; 0.08 to 49) years and 95.8% (249 of 260 patients) were in the pediatric age group. Growth status was evaluated in 258 patients and of them, 27 (10.5%) had growth failure, all cases of which were attributed to non-endocrine reasons. There was a significant correlation between growth failure and serum albumin levels below 3.5 g/dL (p=0.002). Only three of 260 (1.1%) patients had endocrine dysfunction. Of these, one with lecithin-cholesterol acyltransferase deficiency and another with Kearns-Sayre syndrome had diabetes, and one with glycerol kinase deficiency had glucocorticoid deficiency. Endocrine dysfunction in patients with IMDs is relatively rare. For this reason, there is no need to conduct routine endocrine evaluations in most patients with IMDs unless a careful and detailed history and a physical examination point to an endocrine dysfunction.

NUTRIBASE - Data base for Nutritional Evaluation and Dietetic Treatment in Populational Metabolic Diseases

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Silvia Ştefania IANCU

2008-12-01

Full Text Available The nutritional evaluation and diet prescription are laborious and require much time. They need calculations of basic nutritional indices, to precisely diagnose and finally to indicate the proper nutritional recommendations based on demographic, anthropometric, biochemical data and medical history of the patient. Our purpose was to create a new strategic approach to increase the rapid elaboration of nutritional evaluation, calculation of carbohydrate controlled diets and a software implementation. We named the outcome application Nutribase. The application could be used in clinical settings and/or nutritional research environments for calculating the composition of diet in diabetes and other metabolic disturbances, for helping dieticians and nutrition professionals as well as an educational instrument for patients and students. Nutribase (an Access based software collects data on nutritional and biological parameters related to dietary assessment and treatment of the subjects with metabolic diseases but not only, calculates the body mass index, ideal body weight and metabolic requirements of patients, provides ready-made diet models and recommendations according to the calculated metabolic requirements, diagnosis, provides tables of composition of foods (calories, carbohydrates, proteins, lipids, allows an assessment of diet composition per meal, provides a flexible educational instrument for creating or adjusting a diet according to the patients’ preferences, is very much time saving in clinical settings and it may be adapted for epidemiological nutritional studies.

MRI and CT appearances in metabolic encephalopathies due to systemic diseases in adults

International Nuclear Information System (INIS)

Bathla, G.; Hegde, A.N.

2013-01-01

The term encephalopathy refers to a clinical scenario of diffuse brain dysfunction, commonly due to a systemic, metabolic, or toxic derangement. Often the clinical evaluation is unsatisfactory in this scenario and imaging plays an important role in the diagnosis, assessment of treatment response, and prognostication of the disorder. Hence, it is important for radiologists to be familiar with the imaging features of some relatively frequently acquired metabolic encephalopathies encountered in the hospital setting. This study reviews the computed tomography (CT) and magnetic resonance imaging (MRI) features of a number of metabolic encephalopathies that occur as part of systemic diseases in adults. The following conditions are covered in this review: hypoglycaemic encephalopathy, hypoxic ischaemic encephalopathy, non-ketotic hyperglycaemia, hepatic encephalopathy, uraemic encephalopathy, hyperammonaemic encephalopathy, and posterior reversible encephalopathy syndrome. MRI is the imaging method of choice in evaluating these conditions. Due to their high metabolic activity, bilateral basal ganglia changes are evident in the majority of cases. Concurrent imaging abnormalities in other parts of the central nervous system often provide useful diagnostic information about the likely underlying cause of the encephalopathy. Besides this, abnormal signal intensity and diffusion restriction patterns on MRI and MR spectroscopy features may provide important clues as to the diagnosis and guide further management. Frequently, the diagnosis is not straightforward and typical imaging features require correlation with clinical and laboratory data for accurate assessment

BClI polymorphism of the glucocorticoid receptor gene is associated with increased obesity, impaired glucose metabolism and dyslipidaemia in patients with Addison's disease.

Science.gov (United States)

Giordano, Roberta; Marzotti, Stefania; Berardelli, Rita; Karamouzis, Ioannis; Brozzetti, Annalisa; D'Angelo, Valentina; Mengozzi, Giulio; Mandrile, Giorgia; Giachino, Daniela; Migliaretti, Giuseppe; Bini, Vittorio; Falorni, Alberto; Ghigo, Ezio; Arvat, Emanuela

2012-12-01

Although glucocorticoids are essential for health, several studies have shown that glucocorticoids replacement in Addison's disease might be involved in anthropometric and metabolic impairment, with increased cardiovascular risk, namely if conventional doses are used. As the effects of glucocorticoids are mediated by the glucocorticoid receptor, encoded by NR3C1 gene, different polymorphisms in the NR3C1 gene have been linked to altered glucocorticoid sensitivity in general population as well as in patients with obesity or metabolic syndrome. We investigated the impact of glucocorticoid receptor gene polymorphisms, including the BclI, N363S and ER22/23EK variants, on anthropometric parameters (BMI and waist circumference), metabolic profile (HOMA, OGTT and serum lipids) and ACTH levels in 50 patients with Addison's disease (34 women and 16 men, age 20-82 year) under glucocorticoids replacement. Neither N363S nor ER22/23EK variants were significantly associated with anthropometric, metabolic or hormonal parameters, while patients carrying the homozygous BclI polymorphism GG (n = 4) showed higher (P Addison's disease and may contribute, along with other factors, to the increase in central adiposity, impaired glucose metabolism and dyslipidaemia. © 2012 Blackwell Publishing Ltd.

Anethum Graveolens Linn (Umbelliferae) Extract Attenuates Stress ...

African Journals Online (AJOL)

Erah

College of Biomedical and Health Sciences, Department of Biotechnology, Konkuk University, Chungju, Republic of ... anti-stress and cognition-improving effects of A. graveolens extract in a rat model. ..... This work was supported by Konkuk.

A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington’s disease in mice

Science.gov (United States)

Acuña, Aníbal I.; Esparza, Magdalena; Kramm, Carlos; Beltrán, Felipe A.; Parra, Alejandra V.; Cepeda, Carlos; Toro, Carlos A.; Vidal, René L.; Hetz, Claudio; Concha, Ilona I.; Brauchi, Sebastián; Levine, Michael S.; Castro, Maite A.

2013-12-01

Huntington’s disease has been associated with a failure in energy metabolism and oxidative damage. Ascorbic acid is a powerful antioxidant highly concentrated in the brain where it acts as a messenger, modulating neuronal metabolism. Using an electrophysiological approach in R6/2 HD slices, we observe an abnormal ascorbic acid flux from astrocytes to neurons, which is responsible for alterations in neuronal metabolic substrate preferences. Here using striatal neurons derived from knock-in mice expressing mutant huntingtin (STHdhQ cells), we study ascorbic acid transport. When extracellular ascorbic acid concentration increases, as occurs during synaptic activity, ascorbic acid transporter 2 (SVCT2) translocates to the plasma membrane, ensuring optimal ascorbic acid uptake for neurons. In contrast, SVCT2 from cells that mimic HD symptoms (dubbed HD cells) fails to reach the plasma membrane under the same conditions. We reason that an early impairment of ascorbic acid uptake in HD neurons could lead to early metabolic failure promoting neuronal death.

Cardio-Metabolic Benefits of Plant-Based Diets

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Hana Kahleova

2017-08-01

Full Text Available Cardio-metabolic disease, namely ischemic heart disease, stroke, obesity, and type 2 diabetes, represent substantial health and economic burdens. Almost one half of cardio-metabolic deaths in the U.S. might be prevented through proper nutrition. Plant-based (vegetarian and vegan diets are an effective strategy for improving nutrient intake. At the same time, they are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease. Evidence suggests that plant-based diets may reduce the risk of coronary heart disease events by an estimated 40% and the risk of cerebral vascular disease events by 29%. These diets also reduce the risk of developing metabolic syndrome and type 2 diabetes by about one half. Properly planned vegetarian diets are healthful, effective for weight and glycemic control, and provide metabolic and cardiovascular benefits, including reversing atherosclerosis and decreasing blood lipids and blood pressure. The use of plant-based diets as a means of prevention and treatment of cardio-metabolic disease should be promoted through dietary guidelines and recommendations.

Energy metabolism disorders in rare and common diseases. Toward bioenergetic modulation therapy and the training of a new generation of European scientists.

Science.gov (United States)

Rossignol, Rodrigue

2015-06-01

Energy metabolism alterations are found in a large number of rare and common diseases of genetic or environmental origin. The number of patients that could benefit from bioenergetic modulation therapy (BIOMET) is therefore very important and includes individuals with pathologies as diverse as mitochondrial diseases, acute coronary syndrome, chronic kidney disease, asthma or even cancer. Although, the alteration of energy metabolism is disease specific and sometimes patient specific, the strategies for BIOMET could be common and target a series of bioenergetic regulatory mechanisms discussed in this article. An excellent training of scientists in the field of energy metabolism, related human diseases and drug discovery is also crucial to form a young generation of MDs, PHDs and Pharma or CRO-group leaders who will discover novel personalized bioenergetic medicines, through pharmacology, genetics, nutrition or adapted exercise training. The Mitochondrial European Educational Training (MEET) consortium was created to pursue this goal, and we dedicated here a special issue of Organelle in Focus (OiF) to highlight their objectives. A total of 10 OiFs articles constitute this Directed Issue on Mitochondrial Medicine. As part of this editorial article, we asked timely questions to the PR. Jan W. Smeitink, professor of Mitochondrial Medicine and CEO of Khondrion, a mitochondrial medicine company. He shared with us his objectives and strategies for the study of mitochondrial diseases and the identification of future treatments. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevalence of metabolic risk factors in non-alcoholic fatty liver disease

International Nuclear Information System (INIS)

Ashraf, N.; Sarfraz, T.; Mumtaz, Z.; Rizwan, M.

2017-01-01

Objective: To determine the frequency of factors leading to metabolic syndrome among non-alcoholic fatty liver disease (NAFLD) patients at a tertiary care hospital. Study Design: Descriptive cross sectional study. Place and Duration of Study: Department of Medicine, Combined Military Hospital, Kharian. Study was carried out over a period of six months from Jan 2015 to Jun 2015. Material and Methods: A total of 110 patients were included in this study. Past history was taken to rule out alcohol intake, viral and drug induced etiology, to determine the presence of co-morbidities like obesity, type 2 diabetes mellitus, arterial hypertension and dyslipidemia. Physical examination was carried to determine the arterial blood pressure and to determine anthropometric data that is weight, height, body mass index (BMI) and abdominal obesity by measuring waist circumference. Results: Mean age of the patients was 49.95 +- 8.86 years. There were 72 male patients (65.5%) while 38 (34.5%) patients were female. Different metabolic factors were central obesity in 82 patients (74.5%), raised high density lipoprotein (HDL) in 19 patients (17.3%), raised cholesterol in 87 patients (79.1%), raised blood pressure in 65 patients (59.1%) and raised fasting plasma glucose in 82 patients (74.5%). Mean BMI was 26.31 kg/m2 +- 2.68, mean waist circumference was 109.82 cm +- 18.41, mean cholesterol was 237.50 +- 48.47mg/dl, mean systolic blood pressure was 148.88mmHg +- 22.10, mean diastolic blood pressure was 90.41mmHg +- 12.25 and mean fasting plasma glucose was 113.28mg/dl +- 22.80. Stratification with regard to age was carried out. Conclusion: A considerable number of patients with NAFLD had metabolic syndrome. There was a close correlation between NAFLD and metabolic syndrome. (author)

Metabolic syndrome and mortality in stable coronary heart disease: relation to gender

DEFF Research Database (Denmark)

Kragelund, Charlotte; Køber, Lars; Faber, Jens

2007-01-01

BACKGROUND: Metabolic syndrome (MS) is associated with subsequent development of type 2 diabetes and cardiovascular disease in the general population. The impact of MS on mortality in patients with stable coronary heart disease is less well defined, and the association of prognosis to gender...... follow-up of 9.2 years. RESULTS: At follow-up 296 (28%) patients had died. 315 (30%) patients had MS based on the definition by the World Health Organization. Patients with MS more frequently had diabetes and three-vessel disease of the coronary arteries. Men had a more severe risk profile than women....... In a multivariable Cox regression analysis, MS was not associated with excess mortality risk in the overall population [adjusted HR=1.3 (95% CI: 0.7-2.3), p=0.43]. In gender specific analyses MS increased risk of all-cause mortality in women [adjusted HR=2.2 (95% CI: 1.1-4.3), p=0.02], but not in men [adjusted HR=1...

Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Rougemont, D; Baron, J C; Collard, P; Bustany, P; Comar, D; Agid, Y

1983-06-01

Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and /sup 18/F-Fluoro-2-deoxy-D-glucose (/sup 18/FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain.

Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: from sarcopenic obesity to cachexia.

Science.gov (United States)

Biolo, Gianni; Cederholm, Tommy; Muscaritoli, Maurizio

2014-10-01

Skeletal muscle is the most abundant body tissue accounting for many physiological functions. However, muscle mass and functions are not routinely assessed. Sarcopenia is defined as skeletal muscle loss and dysfunction in aging and chronic diseases. Inactivity, inflammation, age-related factors, anorexia and unbalanced nutrition affect changes in skeletal muscle. Mechanisms are difficult to distinguish in individual subjects due to the multifactorial character of the condition. Sarcopenia includes both muscle loss and dysfunction which induce contractile impairment and metabolic and endocrine abnormalities, affecting whole-body metabolism and immune/inflammatory response. There are different metabolic trajectories for muscle loss versus fat changes in aging and chronic diseases. Appetite regulation and physical activity affect energy balance and changes in body fat mass. Appetite regulation by inflammatory mediators is poorly understood. In some patients, inflammation induces anorexia and fat loss in combination with sarcopenia. In others, appetite is maintained, despite activation of systemic inflammation, leading to sarcopenia with normal or increased BMI. Inactivity contributes to sarcopenia and increased fat tissue in aging and diseases. At the end of the metabolic trajectories, cachexia and sarcopenic obesity are paradigms of the two patient categories. Pre-cachexia and cachexia are observed in patients with cancer, chronic heart failure or liver cirrhosis. Sarcopenic obesity and sarcopenia with normal/increased BMI are observed in rheumatoid arthritis, breast cancer patients with adjuvant chemotherapy and in most of patients with COPD or chronic kidney disease. In these conditions, sarcopenia is a powerful prognostic factor for morbidity and mortality, independent of BMI. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Polycystic ovary syndrome and metabolic syndrome.

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Ali, Aus Tariq

2015-08-01

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, where the main clinical features include menstrual irregularities, sub-fertility, hyperandrogenism, and hirsutism. The prevalence of PCOS depends on ethnicity, environmental and genetic factors, as well as the criteria used to define it. On the other hand, metabolic syndrome is a constellation of metabolic disorders which include mainly abdominal obesity, insulin resistance, impaired glucose metabolism, hypertension and dyslipidaemia. These associated disorders directly increase the risk of Type 2 diabetes mellitus (DMT2), coronary heart disease (CHD), cardiovascular diseases (CVD) and endometrial cancer. Many patients with PCOS have features of metabolic syndrome such as visceral obesity, hyperinsulinaemia and insulin resistance. These place patients with PCOS under high risk of developing cardiovascular disease (CVD), Type 2 diabetes (DMT2) and gynecological cancer, in particular, endometrial cancer. Metabolic syndrome is also increased in infertile women with PCOS. The aim of this review is to provide clear and up to date information about PCOS and its relationship with metabolic syndrome, and the possible interaction between different metabolic disorders.

Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.

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Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B; Lee, Young Mok; Chou, Janice Y; Byrne, Barry J; Correia, Catherine E; Mah, Cathryn S; Weinstein, David A; Conlon, Thomas J

2011-01-01

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

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Andrew Specht

2011-01-01

Full Text Available A canine model of Glycogen storage disease type Ia (GSDIa is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

Possible Link between Metabolic Syndrome and Chronic Kidney Disease in the Development of Cardiovascular Disease

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Kosaku Nitta

2011-01-01

Full Text Available Metabolic syndrome (MetS is a clinical syndrome that consists of visceral obesity, dyslipidemia, hypertension, and impaired insulin sensitivity. Although individual components of MetS have been implicated in the development of chronic kidney disease (CKD, few studies have examined the effect of combinations of the components of MetS on the development of CKD and cardiovascular disease (CVD. The prevalence of MetS is increasing worldwide in both developing and developed countries, and early detection and treatment of MetS would be a cost-effective strategy for preventing the development of CKD. Visceral obesity and insulin resistance are two important features of MetS that may be associated with renal damage. Lifestyle modifications, including caloric restriction and exercise, are necessary to treat MetS. Initial antihypertensive therapy should consist of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. An improved understanding of the mechanism responsible for the association between MetS and renal damage should be helpful in determining the treatment regimens directed at cardiovascular and renal protection.

MR imaging of the brain: metabolic and toxic white matter diseases

International Nuclear Information System (INIS)

Forsting, M.

1999-01-01

Metabolic disorders of the brain are rare, complex and confusing. The diagnostic modality of choice nowadays is MRI. The high diagnostic sensitivity, however, is coupled with a lack of specificity and usually results in the depiction of similar appearing but clinically diverse white matter processes. For this reason it is essential to perform the MRI as early as possible during the course of the disease and to keep in close contact to the referring clinician to optimize image interpretation. Another precondition is to know the natural course of brain myelination and to know how this appears on the individual MR machine with different parameters. In some diseases like phenylketonuria MRI seems to be an excellent tool to monitor dietary treatment and patient compliance. In patients after radio- and / or chemotherapy MRI reveals the radiation induced leucencephalopathy and can usually differentiate between a recurrent malignancy. (orig.)

The metabolism of plant sterols is disturbed in postmenopausal women with coronary artery disease.

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Gylling, Helena; Hallikainen, Maarit; Rajaratnam, Radhakrishnan A; Simonen, Piia; Pihlajamäki, Jussi; Laakso, Markku; Miettinen, Tatu A

2009-03-01

In postmenopausal coronary artery disease (CAD) women, serum plant sterols are elevated. Thus, we investigated further whether serum plant sterols reflect absolute cholesterol metabolism in CAD as in other populations and whether the ABCG5 and ABCG8 genes, associated with plant sterol metabolism, were related to the risk of CAD. In free-living postmenopausal women with (n = 47) and without (n = 62) CAD, serum noncholesterol sterols including plant sterols were analyzed with gas-liquid chromatography, cholesterol absorption with peroral isotopes, absolute cholesterol synthesis with sterol balance technique, and bile acid synthesis with quantitating fecal bile acids. In CAD women, serum plant sterol ratios to cholesterol were 21% to 26% (P synthesis were reduced. Only in controls were serum plant sterols related to cholesterol absorption (eg, sitosterol; in controls: r = 0.533, P synthesis marker) and lathosterol-cholestanol (relative synthesis-absorption marker) were related to absolute synthesis and absorption percentage (P range from .05 to sterol metabolism is disturbed in CAD women; so serum plant sterols only tended to reflect absolute cholesterol absorption. Other relative markers of cholesterol metabolism were related to the absolute ones in both groups. ABCG5 and ABCG8 genes were not associated with the risk of CAD.

Heterogeneity of elderly depression: increased risk of Alzheimer's disease and Aβ protein metabolism.

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Namekawa, Yuki; Baba, Hajime; Maeshima, Hitoshi; Nakano, Yoshiyuki; Satomura, Emi; Takebayashi, Naoko; Nomoto, Hiroshi; Suzuki, Toshihito; Arai, Heii

2013-06-03

Epidemiological studies have proposed that depression may increase the risk for Alzheimer's disease (AD), even in patients with early-onset depression. Although metabolism of amyloid β protein (Aβ) in elderly depression received attention in terms of their correlation, there is a serious heterogeneity in elderly depression in terms of age at onset of depression. Moreover, it is unknown whether early-onset major depressive disorder (MDD) has a long-term effect on the involvement of Aβ metabolism and later development of AD. Thus, we evaluated serum Aβ40 and Aβ42 levels, the Aβ40/Aβ42 ratio in 89 elderly (≥60 years of age) inpatients with MDD and 81 age-matched healthy controls, and compared them among patients with early-onset (great interest that the serum Aβ40/Aβ42 ratio was negatively correlated with the age at MDD onset (R=-0.201, p=0.032). These results suggest that an earlier onset of MDD may have a more serious abnormality in Aβ metabolism, possibly explaining a biological mechanism underlying the link between depression and AD. Copyright © 2012 Elsevier Inc. All rights reserved.

Risk assessment of postpartum uterine disease and consequences of puerperal metritis for subsequent metabolic status, reproduction and milk yield in dairy cows.

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Konyves, László; Szenci, Ottó; Jurkovich, Viktor; Tegzes, Lászlóné; Tirián, Attila; Solymosi, Norbert; Gyulay, Gyula; Brydl, Endre

2009-03-01

The objective of this study was to determine some metabolic and other factors predicting the risk of postpartum uterine disease (PUD), and the effects of puerperal metritis (PM) on metabolic status, reproduction and milk yield were analysed. A total of 105 Holstein-Friesian cows were included, and sampled on day metabolic tests. From day 4 the development of PUD, and from days 28-35 the ovarian activity was monitored. When grade > or = 1 + ketonuria was present on day 4 postpartum, this indicated a higher probability of PUD [odds ratio (OR) 2.64; P 0.200 mmol/l on days diseases (OR: 3.44; P or = 1.0 occurred between days cows with retained placenta. The risk of uterine diseases was lower in multiparous than in primiparous cows (OR: 0.29; P Cows affected with PM (PM+ cows) showed lower milk production on day 4 (kg; P cows.

Metabolically Healthy Obesity and Ischemic Heart Disease: A 10-Year Follow-Up of the Inter99 Study.

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Hansen, Louise; Netterstrøm, Marie K; Johansen, Nanna B; Rønn, Pernille F; Vistisen, Dorte; Husemoen, Lise L N; Jørgensen, Marit E; Rod, Naja H; Færch, Kristine

2017-06-01

Recent studies have suggested that a subgroup of obese individuals is not at increased risk of obesity-related complications. This subgroup has been referred to as metabolically healthy obese. To investigate whether obesity is a risk factor for development of ischemic heart disease (IHD) irrespective of metabolic health. In all, 6238 men and women from the Danish prospective Inter99 study were followed during 10.6 (standard deviation = 1.7) years. General community. Participants were classified according to body mass index and four metabolic risk factors (low high-density lipoprotein cholesterol, elevated blood pressure, triglycerides, and fasting plasma glucose). Metabolically healthy individuals were defined as having no metabolic risk factors, and metabolically unhealthy individuals were defined as having a minimum of one. IHD. During follow-up, 323 participants developed IHD. Metabolically healthy obese men had increased risk of IHD compared with metabolically healthy normal-weight men [hazard ratio (HR), 3.1; 95% confidence interval (CI), 1.1 to 8.2)]. The corresponding results for women were less pronounced (HR, 1.8; 95% CI, 0.7 to 4.8). Being metabolically healthy but overweight was not associated with higher risk of IHD in men (HR, 1.1; 95% CI, 0.5 to 2.4), and in women the risk was only slightly increased and insignificant (HR, 1.5; 95% CI, 0.8 to 3.0). A substantial proportion of metabolically healthy individuals became metabolically unhealthy after 5 years of follow-up. When these changes in exposure status were taken into account, slightly higher risk estimates were found. Being obese is associated with higher incidence of IHD irrespective of metabolic status, and we question the feasibility of denoting a subgroup of obese individuals as metabolically healthy. Copyright © 2017 Endocrine Society

Serum Compounds of Energy Metabolism Impairment Are Related to Disability, Disease Course and Neuroimaging in Multiple Sclerosis.

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Lazzarino, Giacomo; Amorini, Angela M; Petzold, Axel; Gasperini, Claudio; Ruggieri, Serena; Quartuccio, Maria Esmeralda; Lazzarino, Giuseppe; Di Stasio, Enrico; Tavazzi, Barbara

2017-11-01

Multiple sclerosis (MS) is characterized by primary inflammation, demyelination, and progressive neurodegeneration. A biochemical MS feature is neuronal mitochondrial dysfunction, compensated by anaerobic metabolism increase, likely aggravating progression of neurodegeneration. Here, we characterized a pragmatic serum profile of compounds related to mitochondrial energy metabolism of potential clinical use. Blood samples of 518 well characterized (disability, disease course) MS patients and 167 healthy controls were analyzed for serum purines, pyrimidines, creatinine, and lactate. Nine of the 15 compounds assayed, hypoxanthine, xanthine, uric acid, inosine, uracil, β-pseudouridine, uridine, creatinine, and lactate, differed significantly between MS patients and controls (p < 0.0001). Using these nine compounds, a unifying Biomarker Score was calculated. Controls and MS patients had mean Biomarker Scores of 0.4 ± 0.7 and 4.4 ± 1.9, respectively (p < 0.00001). The Biomarker Score was higher in patients with progressive (6.0 ± 1.8 than with relapsing remitting disease course (3.6 ± 1.5, p < 0.00001). High association between the Biomarker Score and increase in disability (EDSS) was also observed. Additionally, in 50 patients who underwent magnetic resonance imaging (MRI), increase in the Biomarker Score correlated to neuroanatomical alterations. These results, obtained in a large cohort of MS patients evaluated for serum metabolic compounds connected to energy metabolism, demonstrated that the Biomarker Score might represent a pragmatic, resource saving, easy to obtain, laboratory tool useful to monitor MS patients and predict at an early stage who will switch from an RR to a progressive disease course. For the first time, it was also clearly shown a link between mitochondrial dysfunction and MRI lesions characteristic of MS.

Organization of metabolic pathways in vastus lateralis of patients with chronic obstructive pulmonary disease.

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Green, Howard J; Bombardier, Eric; Burnett, Margaret; Iqbal, Sobia; D'Arsigny, Christine L; O'Donnell, Dennis E; Ouyang, Jing; Webb, Katherine A

2008-09-01

The objective of this study was to determine whether patients with chronic obstructive lung disease (COPD) display differences in organization of the metabolic pathways and segments involved in energy supply compared with healthy control subjects. Metabolic pathway potential, based on the measurement of the maximal activity (V(max)) of representative enzymes, was assessed in tissue extracted from the vastus lateralis in seven patients with COPD (age 67 +/- 4 yr; FEV(1)/FVC = 44 +/- 3%, where FEV(1) is forced expiratory volume in 1 s and FVC is forced vital capacity; means +/- SE) and nine healthy age-matched controls (age 68 +/- 2 yr; FEV(1)/FVC = 75 +/- 2%). Compared with control, the COPD patients displayed lower (P chain and glycogenolysis and glycolysis relative to beta-oxidation.

Marchiafava-Bignami disease with dementia: severe cerebral metabolic depression revealed by PET. Case report

International Nuclear Information System (INIS)

Pappata, S.; Chabriat, H.; Levasseur, M.; Legault-Demare, F.; Baron, J.C.

1994-01-01

The Cerebral Metabolic Rate of Glucose (CMRGlu) was measured with positron emission tomography and 18 F-FDG in a patient with Marchiafava-Bignami Disease (MBD)-related dementia. Despite MRI evidence of lesions essentially limited to the corpus callosum (CC), but consistent with the cognitive pattern of cortical dementia, the CMRGlu was markedly reduced in the frontal and temporo-parieto-occipital association cortices. Disruption of cortico-cortical networks crossing the CC presumably contributed to, but may not in and by itself explain, the severity of the clinical-metabolic findings in this patient. An additional role could be played by microscopic white matter lesions and/or neocortical neuronal loss, which have been occasionally observed in post-mortem studies of MBD patients. (authors)

Use of intrinsic fluorescent signals for characterizing tissue metabolic states in health and disease

Science.gov (United States)

Chance, Britton

1996-04-01

The large content of mitochondria in metabolizing cells, coupled with intrinsic NADH and flavoprotein signals makes these signals ideal for characterizing tissue metabolic states in health and disease. The first few millimeters of tissue are reached by the fluorescence excitation in the exposed surfaces of the cervix, bladder, rectum and esophagus, etc. Thus, extensive use has been made of fluorescent signals by a large number of investigators for tumor diagnosis from an empirical standpoint where the fluorescent signals are generally diminished in precancerous and cancerous tissue. This article reviews the biochemical basis for the fluorescent signals and points to a 'gold standard' for fluorescent signal examination involving freeze trapping and low temperature two- or three-dimensional high resolution fluorescence spectroscopy.

Clinical evaluation of 99Tcm-MIBI myocardial perfusion imaging for the detection of coronary artery disease in patients with metabolic syndrome

International Nuclear Information System (INIS)

Tian Yueqin; Wei Hongxing; Guo Xinhua; Guo Feng; He Zuoxiang

2008-01-01

Objective: Metabolic syndrome is a combination of medical disorders that consist of a collection of independent factors at risk of developing coronary artery disease. The purpose of this study was to evaluate the value of 99 Tc m -methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging for the diagnosis of coronary artery disease in patients with metabolic syndrome. Methods: A total of 251 patients [mean age (59 ± 10) years, 179 men, 72 women] were included in this study. All patients underwent exercise and rest 99 Tc m -MIBI myocardial perfusion imaging and coronary angiography. Results: Of the 163 patients with significant coronary artery stenosis, 116 showed abnormal 99 Tc m -MIBI myocardial perfusion imaging; and among the 88 patients with normal coronary angiography, 82 showed normal myocardial perfusion imaging. The sensitivity, specificity and accuracy of 99 Tc m -MIBI myocardial perfusion imaging for coronary artery disease detection were 71% (116/163), 93% (82/88) and 79% (198/251), respectively. The positive and negative predictive values were 95% (116/122) and 64% (82/129), respectively. Conclusion: 99 Tc m -MIBI myocardial perfusion imaging has important clinical value for detecting coronary artery disease in patients with metabolic syndrome. (authors)

Fibroblast Growth Factor Signaling in Metabolic Regulation.

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Nies, Vera J M; Sancar, Gencer; Liu, Weilin; van Zutphen, Tim; Struik, Dicky; Yu, Ruth T; Atkins, Annette R; Evans, Ronald M; Jonker, Johan W; Downes, Michael Robert

2015-01-01

The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance, and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed. In this review, we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also, the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease and to provide starting points for the development of FGF-based therapies against metabolic conditions.

Fibroblast growth factor signaling in metabolic regulation

Directory of Open Access Journals (Sweden)

Vera eNies

2016-01-01

Full Text Available The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases, and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed.In this review we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease, and to provide starting points for the development of FGF-based therapies against metabolic conditions.

Gout and Metabolic Syndrome: a Tangled Web.

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Thottam, Gabrielle E; Krasnokutsky, Svetlana; Pillinger, Michael H

2017-08-26

The complexity of gout continues to unravel with each new investigation. Gout sits at the intersection of multiple intrinsically complex processes, and its prevalence, impact on healthcare costs, and association with important co-morbidities make it increasingly relevant. The association between gout and type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, renal disease, and obesity suggest that either gout, or its necessary precursor hyperuricemia, may play an important role in the manifestations of the metabolic syndrome. In this review, we analyze the complex interconnections between gout and metabolic syndrome, by reviewing gout's physiologic and epidemiologic relationships with its major co-morbidities. Increasing evidence supports gout's association with metabolic syndrome. More specifically, both human studies and animal models suggest that hyperuricemia may play a role in promoting inflammation, hypertension and cardiovascular disease, adipogenesis and lipogenesis, insulin and glucose dysregulation, and liver disease. Fructose ingestion is associated with increased rates of hypertension, weight gain, impaired glucose tolerance, and dyslipidemia and is a key driver of urate biosynthesis. AMP kinase (AMPK) is a central regulator of processes that tend to mitigate against the metabolic syndrome. Within hepatocytes, leukocytes, and other cells, a fructose/urate metabolic loop drives key inhibitors of AMPK, including AMP deaminase and fructokinase, that may tilt the balance toward metabolic syndrome progression. Preliminary evidence suggests that agents that block the intracellular synthesis of urate may restore AMPK activity and help maintain metabolic homeostasis. Gout is both an inflammatory and a metabolic disease. With further investigation of urate's role, the possibility of proper gout management additionally mitigating metabolic syndrome is an evolving and important question.

Genetics and genomics of cholesterol and polyunsaturated fatty acid metabolism in relation to coronary heart disease risk

NARCIS (Netherlands)

Lu Yingchang (Kevin), Y.

2011-01-01

Background

Coronary heart disease (CHD) continues to be a leading cause of morbidity and mortality among adults worldwide. Deregulated lipid metabolism (dyslipidemia) that manifests as hypercholesterolemia, hypertriglyceridemia, low high-density-lipoprotein (HDL)

Gut Microbiota and Metabolic Disorders

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Kyu Yeon Hur

2015-06-01

Full Text Available Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.

Concurrence of High Fat Diet and APOE Gene Induces Allele Specific Metabolic and Mental Stress Changes in a Mouse Model of Alzheimer's Disease.

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Segev, Yifat; Livne, Adva; Mints, Meshi; Rosenblum, Kobi

2016-01-01

Aging is the main risk factor for neurodegenerative diseases, including Alzheimer's disease (AD). However, evidence indicates that the pathological process begins long before actual cognitive or pathological symptoms are apparent. The long asymptomatic phase and complex integration between genetic, environmental and metabolic factors make it one of the most challenging diseases to understand and cure. In the present study, we asked whether an environmental factor such as high-fat (HF) diet would synergize with a genetic factor to affect the metabolic and cognitive state in the Apolipoprotein E (ApoE4) mouse model of AD. Our data suggest that a HF diet induces diabetes mellitus (DM)-like metabolism in ApoE4 mice, as well as changes in β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) protein levels between the two ApoE strains. Furthermore, HF diet induces anxiety in this AD mouse model. Our results suggest that young ApoE4 carriers are prone to psychological stress and metabolic abnormalities related to AD, which can easily be triggered via HF nutrition.

The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease

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Marit K. Zinöcker

2018-03-01

Full Text Available The dietary pattern that characterizes the Western diet is strongly associated with obesity and related metabolic diseases, but biological mechanisms supporting these associations remain largely unknown. We argue that the Western diet promotes inflammation that arises from both structural and behavioral changes in the resident microbiome. The environment created in the gut by ultra-processed foods, a hallmark of the Western diet, is an evolutionarily unique selection ground for microbes that can promote diverse forms of inflammatory disease. Recognizing the importance of the microbiome in the development of diet-related disease has implications for future research, public dietary advice as well as food production practices. Research into food patterns suggests that whole foods are a common denominator of diets associated with a low level of diet-related disease. Hence, by studying how ultra-processing changes the properties of whole foods and how these foods affect the gut microbiome, more useful dietary guidelines can be made. Innovations in food production should be focusing on enabling health in the super-organism of man and microbe, and stronger regulation of potentially hazardous components of food products is warranted.

EVALUATION OF METABOLIC SYNDROME, ITS CORRELATION WITH CLINICAL AND ANGIOGRAPHIC PROFILE IN PATIENTS WITH CORONARY ARTERY DISEASE- A PROSPECTIVE STUDY AT TERTIARY HOSPITAL

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Eruvaram Srikanth

2016-10-01

Full Text Available BACKGROUND Coronary artery disease has a major share for cardiovascular disease in a developing country like India, which is in epidemic proportion. There are number of risk factors for development of coronary artery disease. According to INTERHEART study, there were 9 modifiable risk factors with population attributable risk of 90 percent in men and 94 percent in women. Metabolic syndrome cluster of risk factors, which include insulin resistance, subclinical inflammation, increased future risk of diabetes and coronary artery disease. In south Asian people are increased tendency to develop metabolic syndrome because of their high percentage of body fat, abdominal obesity and insulin resistance. Metabolic syndrome has more mortality and morbidity from CAD. It is desirable identifying this subset of patients, which could improve patient or physician adherence to risk-reducing behaviours or interventions and improve clinical outcomes. There are reports in literature on association inflammatory markers and insulin resistance with severity of disease in CAD. There are few studies, which correlated severity of CAD with SYNTAX score in patients with metabolic syndrome, so in these study prospectively evaluated clinical and angiographic profile in patients with CAD in subset patients with metabolic syndrome, CAD severity was assessed with SYNTAX scoring system and thrombus burden was evaluated. MATERIALS AND METHODS Among 101 patients who were diagnosed to have metabolic syndrome according to ATP III guidelines were evaluated in the study. All patients were evaluated by clinical examination including waist circumference, body mass index, routine blood investigations were carried out. Lipid profile, ECG and 2D echo was done. Then, patients were evaluated with coronary angiogram and among patients who underwent coronary angiography, the lesions were classified according to AHA/ACC classification into type A, type B and type C for assessing lesion

Emerging opportunities for the treatment of metabolic diseases

DEFF Research Database (Denmark)

Finan, Brian; Clemmensen, Christoffer; Müller, Timo D

2015-01-01

with integrated activities derived from multiple hormones involved in the physiological control of metabolism have emerged as one of the more promising candidates for reversing obesity. The inclusion of glucagon-like peptide-1 (GLP-1) as one of the constituents is a unifying factor amongst the majority......Obesity is a pathogenic gateway to the metabolic syndrome and the complications thereof, thus interventions aimed at preventing or reversing the metabolic derangements underlying obesity hold great therapeutic promise. However, the complexity of energy balance regulation, combined...

Structural changes in the liver in metabolic syndrome

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D. V. Vasendin

2015-01-01

Full Text Available Scientifically proven close relationship of nonalcoholic fatty liver disease with development of metabolic syndrome and its individual components involves the conclusion that the target organ in metabolic symptom, even regardless of the severity of obesity, the liver occupies a dominant position, as the body undergoes the first characteristic of non-alcoholic fatty liver disease changes, involving violation of metabolism in the body. Dislipoproteinemia plays an important role in the formation of metabolic syndrome in obesity and other obesity-associated diseases. Altered liver function are the root cause of violations of processes of lipid metabolism and, consequently, abnormal functioning of the liver may be a separate, additional and independent risk factor for development of dyslipidemia and obesity as the main component of the metabolic syndrome.

Metabolic predictors of peri-partum diseases and their association with parity in dairy cows.

Science.gov (United States)

Ruprechter, Gretel; Adrien, Maria de Lourdes; Larriestra, Alejandro; Meotti, Otavio; Batista, Chester; Meikle, Ana; Noro, Mirela

2018-02-19

The predictive values of plasma non-esterified fatty acid (NEFA), beta-hydroxybutyrate (BHB), cholesterol, albumin and calcium to predict risk of peripartum diseases in primiparous (PP) and multiparous (MP) Holstein cows was investigated. Besides it was assessed if the health status interacted with parity on body condition score and metabolic profiles during the transition period. Dairy cows (126 PP and 182 MP) from a commercial dairy free stall herd (loose-housing system) were weekly body condition scored and tail bled for metabolites determination from -3 to +4 weeks relative to calving. Peripartum diseases were diagnosed by a single trained veterinarian, while subclinical diseases (ketosis and hypocalcemia) were diagnosed at the laboratory. Cows were classified as healthy cows, cows with one event, or cows with two clinical events following a prospective observational cohort study, with only healthy cows enrolled at the beginning of the study. The largest incidence was for metritis (26.6%) followed by retained placenta (17.2%) and mastitis (15.2%) with no effect of parity, while subclinical hypocalcemia incidence was greater in MP than PP cows (43% vs 9.5%) respectively. In MP cows albumin concentrations were predictive for metritis at week -2 and for retained placenta at weeks -2 and -1, while cholesterol was predictive for mastitis at week -2, -1 and at calving. The interaction between health status and parity affected all metabolites during the transition period. This study showed a different evolution of metabolic profiles in healthy and sick cows during the transition according to parity, pointing out albumin and cholesterol as diseases predictors before calving. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

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Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

2016-07-26

Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

Metabolic syndrome in patients with peripheral arterial disease.

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Estirado, E; Lahoz, C; Laguna, F; García-Iglesias, F; González-Alegre, M T; Mostaza, J M

2014-11-01

The prevalence of metabolic syndrome (MS) in patients with peripheral arterial disease (PAD) and coronary or cerebrovascular disease is increasing, but it is not known whether this association also exists in patients with isolated PAD. The aim of the current study was to assess the prevalence of MS in patients with PAD who had no coronary or cerebrovascular disease, the prescription rate of evidence-based cardiovascular therapies and the attainment of therapeutic goals in patients with PAD and with and without MS. Multicenter, cross-sectional study of 3.934 patients aged ≥ 45 years with isolated PAD who were treated in primary care and specialized outpatient clinics during 2009. A diagnosis of PAD was reached for ankle brachial indices <0.9, a previous history of amputation or revascularization. In the overall population, the mean age was 67.6 years, 73.8% were males and 63% had MS (95% CI 61.5-64.3%). Patients with MS had a higher prevalence of cardiovascular risk factors and comorbidities, more severe PAD and higher prescription rate of evidence-based cardiovascular therapies. After adjusting for risk factors and comorbidity, there was a more frequent use of renin-angiotensin system blockers, beta-blockers, diuretics and statins among the patients with MS. A lower percentage of patients with MS achieved the therapeutic goals for blood pressure (22% vs. 41.5%, p<0.001). Similarly, a lower percentage of patients with diabetes achieved the glycated hemoglobin goals (44% vs. 53.1%, p<0.001), with no differences in LDL-cholesterol levels (29.8% vs. 39.1%, p=0.265). Patients with PAD have a high prevalence of MS. Patients with MS do not attain therapeutic goals as frequently as those without, despite taking more cardiovascular drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Metabolic Diseases Downregulate the Majority of Histone Modification Enzymes, Making a Few Upregulated Enzymes Novel Therapeutic Targets--"Sand Out and Gold Stays".

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Shao, Ying; Chernaya, Valeria; Johnson, Candice; Yang, William Y; Cueto, Ramon; Sha, Xiaojin; Zhang, Yi; Qin, Xuebin; Sun, Jianxin; Choi, Eric T; Wang, Hong; Yang, Xiao-feng

2016-02-01

To determine whether the expression of histone modification enzymes is regulated in physiological and pathological conditions, we took an experimental database mining approach pioneered in our labs to determine a panoramic expression profile of 164 enzymes in 19 human and 17 murine tissues. We have made the following significant findings: (1) Histone enzymes are differentially expressed in cardiovascular, immune, and other tissues; (2) our new pyramid model showed that heart and T cells are among a few tissues in which histone acetylation/deacetylation, and histone methylation/demethylation are in the highest varieties; and (3) histone enzymes are more downregulated than upregulated in metabolic diseases and regulatory T cell (Treg) polarization/ differentiation, but not in tumors. These results have demonstrated a new working model of "Sand out and Gold stays," where more downregulation than upregulation of histone enzymes in metabolic diseases makes a few upregulated enzymes the potential novel therapeutic targets in metabolic diseases and Treg activity.

MR imaging of the brain: metabolic and toxic white matter diseases

Energy Technology Data Exchange (ETDEWEB)

Forsting, M. [Univ. of Essen (Germany). Dept. of Neuroradiology

1999-08-01

Metabolic disorders of the brain are rare, complex and confusing. The diagnostic modality of choice nowadays is MRI. The high diagnostic sensitivity, however, is coupled with a lack of specificity and usually results in the depiction of similar appearing but clinically diverse white matter processes. For this reason it is essential to perform the MRI as early as possible during the course of the disease and to keep in close contact to the referring clinician to optimize image interpretation. Another precondition is to know the natural course of brain myelination and to know how this appears on the individual MR machine with different parameters. In some diseases like phenylketonuria MRI seems to be an excellent tool to monitor dietary treatment and patient compliance. In patients after radio- and / or chemotherapy MRI reveals the radiation induced leucencephalopathy and can usually differentiate between a recurrent malignancy. (orig.) With 3 figs., 1 tab., 23 refs.

Therapeutic strategies for metabolic diseases: Small-molecule diacylglycerol acyltransferase (DGAT) inhibitors.

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Naik, Ravi; Obiang-Obounou, Brice W; Kim, Minkyoung; Choi, Yongseok; Lee, Hyun Sun; Lee, Kyeong

2014-11-01

Metabolic diseases such as atherogenic dyslipidemia, hepatic steatosis, obesity, and type II diabetes are emerging as major global health problems. Acyl-CoA:diacylglycerol acyltransferase (DGAT) is responsible for catalyzing the final reaction in the glycerol phosphate pathway of triglycerol synthesis. It has two isoforms, DGAT-1 and DGAT-2, which are widely expressed and present in white adipose tissue. DGAT-1 is most highly expressed in the small intestine, whereas DGAT-2 is primarily expressed in the liver. Therefore, the selective inhibition of DGAT-1 has become an attractive target with growing potential for the treatment of obesity and type II diabetes. Furthermore, DGAT-2 has been suggested as a new target for the treatment of DGAT-2-related liver diseases including hepatic steatosis, hepatic injury, and fibrosis. In view the discovery of drugs that target DGAT, herein we attempt to provide insight into the scope and further reasons for optimization of DGAT inhibitors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sirtuins: Novel targets for metabolic disease in drug development

International Nuclear Information System (INIS)

Jiang Weijian

2008-01-01

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases such as type 2 diabetes. SIRT1, an NAD + -dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produces beneficial effects on glucose homeostasis and insulin sensitivity. Activation of SIRT1 leads to enhanced activity of multiple proteins, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) and FOXO which helps to mediate some of the in vitro and in vivo effects of sirtuins. Resveratrol, a polyphenolic SIRT1 activator, mimics the effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance. In this review, we summarize recent research advances in unveiling the molecular mechanisms that underpin sirtuin as therapeutic candidates and discuss the possibility of using resveratrol as potential drug for treatment of diabetes

Metabolic Mechanisms in Obesity and Type 2 Diabetes: Insights from Bariatric/Metabolic Surgery

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Adriana Florinela Cătoi

2015-11-01

Full Text Available Obesity and the related diabetes epidemics represent a real concern worldwide. Bariatric/metabolic surgery emerged in last years as a valuable therapeutic option for obesity and related diseases, including type 2 diabetes mellitus (T2DM. The complicated network of mechanisms involved in obesity and T2DM have not completely defined yet. There is still a debate on which would be the first metabolic defect leading to metabolic deterioration: insulin resistance or hyperinsulinemia? Insight into the metabolic effects of bariatric/metabolic surgery has revealed that, beyond weight loss and food restriction, other mechanisms can be activated by the rearrangements of the gastrointestinal tract, such as the incretinic/anti-incretinic system, changes in bile acid composition and flow, and modifications of gut microbiota; all of them possibly involved in the remission of T2DM. The complete elucidation of these mechanisms will lead to a better understanding of the pathogenesis of this disease. Our aim was to review some of the metabolic mechanisms involved in the development of T2DM in obese patients as well as in the remission of this condition in patients submitted to bariatric/metabolic surgery.

Metabolic assessment and enteral tube feeding usage in children with acute neurological diseases

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Heitor Pons Leite

Full Text Available OBJECTIVE: To report on acquired experience of metabolic support for children with acute neurological diseases, emphasizing enteral tube feeding usage and metabolic assessment, and also to recommend policies aimed towards improving its implementation. DESIGN: Retrospective analysis. SETTING: Pediatric Intensive Care Unit of Hospital do Servidor Público Estadual de São Paulo. SUBJECTS: 44 patients consecutively admitted to the Pediatric ICU over a period of 3 years who were given nutrition and metabolic support for at least 72 hours. Head trauma, CNS infections and craniotomy post-operative period following tumor exeresis were the main diagnoses. MEASUREMENTS: Records of protein-energy intake, nutrient supply route, nitrogen balance and length of therapy. RESULTS: From a total of 527 days of therapy, single parenteral nutrition was utilized for 34.3% and single enteral tube feeding for 79.1% of that period. 61.4% of the children were fed exclusively via enteral tube feeding, 9.1% via parenteral and 39.5 % by both routes. The enteral tube feeding was introduced upon admission and transpyloric placement was successful in 90% of the cases. Feeding was started 48 hours after ICU admission. The caloric goal was achieved on the 7th day after admission, and thereafter parenteral nutrition was interrupted. The maximum energy supply was 104.2 ± 23.15 kcal/kg. The median length of therapy was 11 days (range 4-38. None of the patients on tube feeding developed GI tract bleeding, pneumonia or bronchoaspiration episodes and, of the 4 patients who were given exclusive TPN, 2 developed peptic ulcer. The initial urinary urea nitrogen was 7.11 g/m2 and at discharge 6.44 g/m2. The protein supply increased from 1.49 g/kg to 3.65 g/kg (p< 0.01. The nitrogen balance increased from -7.05 to 2.2 g (p< 0.01. CONCLUSIONS: Children with acute neurological diseases are hypercatabolic and have high urinary nitrogen losses. The initial negative nitrogen balance can be

Bile Acid Metabolism in Liver Pathobiology

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Chiang, John Y. L.; Ferrell, Jessica M.

2018-01-01

Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism. The gut-to-liver axis plays a critical role in the regulation of enterohepatic circulation of bile acids, bile acid pool size, and bile acid composition. Bile acids control gut bacteria overgrowth, and gut bacteria metabolize bile acids to regulate host metabolism. Alteration of bile acid metabolism by high-fat diets, sleep disruption, alcohol, and drugs reshapes gut microbiome and causes dysbiosis, obesity, and metabolic disorders. Gender differences in bile acid metabolism, FXR signaling, and gut microbiota have been linked to higher prevalence of fatty liver disease and hepatocellular carcinoma in males. Alteration of bile acid homeostasis contributes to cholestatic liver diseases, inflammatory diseases in the digestive system, obesity, and diabetes. Bile acid-activated receptors are potential therapeutic targets for developing drugs to treat metabolic disorders. PMID:29325602

Prevalence of chronic kidney disease in adults with metabolic syndrome

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P C Emem-Chioma

2011-01-01

Full Text Available The burden of chronic kidney disease (CKD and other non- communicable diseases continues to rise globally, and recent studies suggest that metabolic syndrome (MS may add to this burden by contributing to the development of CKD. Given that reports on the prevalence of CKD in patients with MS in this environment are scanty, this study was undertaken with the sole aim of determining the prevalence of CKD in subjects with MS as defined by the International Diabetes Federation (IDF and the National Cholesterol Education Project Adult Treatment Panel III (NCEP ATP III. A total of 240 consenting adults (18-70 years attending the general out- patient clinic of the General Hospital Okrika for various ailments were studied. Subjects were screened for MS as per the above- mentioned criteria. Estimated GFR (eGFR was determined with Modification of Diet for Renal Disease (MDRD formula and CKD was defined as eGFR less than 60 mL/min/1.73 m2 . Data was analyzed using SPSS version 12.0 and Epi info version 4.06d; P 0.05. CKD was more common in subjects with MS compared with those without, although the difference was not statistically significant. The prevalence of CKD in subjects with MS in our study population did not differ significantly when the different MS definitions were employed.

Use of isotopically radiolabelled GM3 ganglioside to study metabolic alterations in Salla disease

International Nuclear Information System (INIS)

Chigorno, Vanna; Valsecchi, Manuela; Nicolini, Marco; Sonnino, Sandro

1997-01-01

We report the preparation of radioactive GM3 ganglioside and its use in the study of sialic acid storage disorders. For the first time GM3 was isotopically radiolabelled in three positions of the molecule: at the sialic acid acetyl group, [ 3 H-Neu5Ac]GM3, at the Cl of the fatty acid moiety, [ 1 4C-Stearoyl]GM3, and at C3 of sphingosine, [ 3 H-Sph]GM3. The radioactive GM3 administered to cultured human fibroblasts from a patient suffering from Salla disease was taken up by the cells and metabolized. An analysis of the distribution of radioactivity within the ganglioside metabolic derivatives showed an accumulation of free sialic acid and ceramide in the pathological cells. (author). 25 refs., 2 figs., 1 tab

Crosstalk between inflammation, iron metabolism and endothelial function in Behçet's disease.

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Oliveira, Rita; Napoleão, Patricia; Banha, João; Paixão, Eleonora; Bettencourt, Andreia; da Silva, Berta Martins; Pereira, Dina; Barcelos, Filipe; Teixeira, Ana; Patto, José Vaz; Viegas-Crespo, Ana Maria; Costa, Luciana

2014-01-01

Behçet's disease (BD) is a rare chronic vasculitis of unclear etiology. It has been suggested that inflammatory response has an important role in BD pathophysiology. Herein, we aimed to study the interplay between inflammation, iron metabolism and endothelial function in BD and search for its putative association with disease activity. Twenty five patients clinically diagnosed with BD were selected and twenty four healthy age-sex matched individuals participated as controls. Results showed an increase of total number of circulating white blood cells and neutrophils, serum transferrin, total iron binding capacity, mieloperoxidase (MPO), ceruloplasmin (Cp), C reactive protein, β2 microglobulin and Cp surface expression in peripheral blood monocytes in BD patients comparatively to healthy individuals (p < 0,05). Of notice, the alterations observed were associated to disease activity status. No significant differences between the two groups were found in serum nitric oxide concentration. The results obtained suggest an important contribution from innate immunity in the pathogenesis of this disease. In particular, surface expression of leukocyte-derived Cp may constitute a new and relevant biomarker to understand BD etiology.