WorldWideScience

Sample records for metabolic diseases

  1. Microelements and inherited metabolic diseases.

    Science.gov (United States)

    Marklová, Eliska

    2002-01-01

    In addition to the main groups of inherited metabolic diseases, including mitochondrial, peroxisomal and lysosomal defects, organic acidurias, porphyrias, defects of amino acids, saccharides and fatty acids metabolism, disorders of transport and utilisation of microelements have also been recognized. Recent findings concerning hereditary hemochromatosis (iron), Wilson and Menkes diseases (copper), molybdenum cofactor deficiency (molybdenum), defects of cobalamine synthesis (cobalt) and acrodermatitis enteropathica (zinc) are reviewed.

  2. Cancer as a metabolic disease

    Directory of Open Access Journals (Sweden)

    Shelton Laura M

    2010-01-01

    Full Text Available Abstract Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect, can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.

  3. Metabolic Diseases of Muscle

    Science.gov (United States)

    ... disease, composes and produces music in his home studio. He moved from Michigan to California to pursue ... helps recruit and coordinate in-home help MDA’s public health education program helps you stay abreast of ...

  4. Macrophage Polarization in Metabolism and Metabolic Disease

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    Anna Meiliana

    2013-08-01

    Full Text Available BACKGROUND: Obesity is now recognized as the main cause of the worldwide epidemic of type 2 diabetes. Obesity-associated chronic inflammation is a contributing key factor for type 2 diabetes and cardiovascular disease. Numbers of studies have clearly demonstrated that the immune system and metabolism are highly integrated. CONTENT: Macrophages are an essential component of innate immunity and play a central role in inflammation and host defense. Moreover, these cells have homeostatic functions beyond defense, including tissue remodeling in ontogenesis and orchestration of metabolic functions. Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to interferons (IFNs, toll-like receptor (TLR, or interleukin (IL-4/IL-13 signals, macrophages undergo M1 (classical or M2 (alternative activation. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1, M2 or M2-like polarized activation. SUMMARY: In response to various signals, macrophages may undergo classical M1 activation (stimulated by TLR ligands and IFN-γ or alternative M2 activation (stimulated by IL-4/IL-13; these states mirror the T helper (Th1–Th2 polarization of T cells. Pathology is frequently associated with dynamic changes in macrophage activation, with classically activated M1 cells implicate in initiating and sustaining inflammation, meanwhile M2 or M2-like activated cells associated with resolution or smoldering chronic inflammation. Identification of the mechanisms and molecules that are associated with macrophage plasticity and polarized activation provides a basis for macrophage centered diagnostic and therapeutic strategies. KEYWORDS: obesity, adipose tissue, inflammation, macrophage polarization.

  5. 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.

  6. Metabolic bone disease of prematurity

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    Stacy E. Rustico, MD

    2014-09-01

    Full Text Available Metabolic bone disease (MBD of prematurity remains a significant problem for preterm, chronically ill neonates. The definition and recommendations for screening and treatment of MBD vary in the literature. A recent American Academy of Pediatrics Consensus Statement may help close the gap in institutional variation, but evidence based practice guidelines remain obscure due to lack of normative data and clinical trials for preterm infants. This review highlights mineral homeostasis physiology, current recommendations in screening and monitoring, prevention and treatment strategies, and an added perspective of a bone health team serving a high volume referral neonatal intensive care center.

  7. Ageing, metabolism and cardiovascular disease.

    Science.gov (United States)

    Costantino, Sarah; Paneni, Francesco; Cosentino, Francesco

    2016-04-15

    Age is one of the major risk factors associated with cardiovascular disease (CVD). About one-fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66(Shc) , JunD and NF-kB. This overview will provide the background for attractive molecular targets to prevent age-driven pathology in the vasculature and the heart. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  8. Interaction between stress responses and circadian metabolism in metabolic disease.

    Science.gov (United States)

    Yang, Zhao; Kim, Hyunbae; Ali, Arushana; Zheng, Ze; Zhang, Kezhong

    2017-09-01

    Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and disease. Dysregulated circadian rhythms are closely associated with various human metabolic diseases, including type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease. Modern lifestyles are frequently associated with an irregular circadian rhythm, which poses a significant risk to public health. While the central clock has a set periodicity, circadian oscillators in peripheral organs, particularly in the liver, can be entrained by metabolic alterations or stress cues. At the molecular level, the signal transduction pathways that mediate stress responses interact with, and are often integrated with, the key determinants of circadian oscillation, to maintain metabolic homeostasis under physiological or pathological conditions. In the liver, a number of nuclear receptors or transcriptional regulators, which are regulated by metabolites, hormones, the circadian clock, or environmental stressors, serve as direct links between stress responses and circadian metabolism. In this review, we summarize recent advances in the understanding of the interactions between stress responses (the endoplasmic reticulum (ER) stress response, the oxidative stress response, and the inflammatory response) and circadian metabolism, and the role of these interactions in the development of metabolic diseases.

  9. Metabolic, endocrine, and related bone diseases

    International Nuclear Information System (INIS)

    Rogers, L.F.

    1987-01-01

    Bone is living tissue, and old bone is constantly removed and replaced with new bone. Normally this exchange is in balance, and the mineral content remains relatively constant. This balance may be disturbed as a result of certain metabolic and endocrinologic disorders. The term dystrophy, referring to a disturbance of nutrition, is applied to metabolic and endocrine bone diseases and should be distinguished from the term dysplasia, referring to a disturbance of bone growth. The two terms are easily confused but are not interchangeable. Metabolic bone disease is caused by endocrine imbalance, vitamin deficiency or excess, and other disturbances in bone metabolism leading to osteoporosis and osteomalacia

  10. The cradle of metabolic disease

    OpenAIRE

    Galjaard, Sander

    2015-01-01

    Summary -Vascular development and FETAL body composition during pregnancy- The effects of maternal adiposity (high body mass index - high BMI -), nutrient intake and storage (gestational weight gain - GWG -) and (abnormal) glucose tolerance (gestational diabetes - GDM - ) are regarded important cornerstones in metabolic research in pregnancy. In Chapter 1, I explained, that they play an important role in the development of complications in the mother and the fetus, both short- and long-ter...

  11. Cancer as a mitochondrial metabolic disease.

    Science.gov (United States)

    Seyfried, Thomas N

    2015-01-01

    Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.

  12. Cancer as a Mitochondrial Metabolic Disease

    Directory of Open Access Journals (Sweden)

    Thomas N Seyfried

    2015-07-01

    Full Text Available Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with the somatic mutation theory. In contrast to the somatic mutation theory, emerging evidence suggests that cancer is a mitochondrial metabolic disease, according to the original theory of Otto Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments that relate to the origin of cancer. The evidence from these experiments is difficult to reconcile with the somatic mutation theory, but is consistent with the notion that cancer is primarily a mitochondrial metabolic disease.

  13. Hepatic diseases related to triglyceride metabolism.

    Science.gov (United States)

    Aguilera-Méndez, Asdrubal; Álvarez-Delgado, Carolina; Hernández-Godinez, Daniel; Fernandez-Mejia, Cristina

    2013-10-01

    Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis.

  14. Outline of metabolic diseases in adult neurology.

    Science.gov (United States)

    Mochel, F

    2015-01-01

    Inborn errors of metabolism (IEM) are traditionally defined by enzymatic deficiencies or defects in proteins involved in cellular metabolism. Historically discovered and characterized in children, a growing number of IEM are described in adults, and especially in the field of neurology. In daily practice, it is important to recognize emergency situations as well as neurodegenerative diseases for which a metabolic disease is likely, especially when therapeutic interventions are available. Here, the goal is to provide simple clinical, imaging and biochemical tools that can first orientate towards and then confirm the diagnosis of IEM. General guidelines are presented to treat the most common IEM during metabolic crises - acute encephalopathies with increased plasma ammonia, lactate or homocystein, as well as rhabdomyolysis. Examples of therapeutic strategies currently applied to chronic neurometabolic diseases are also provided - GLUT1 deficiency, adrenoleukodystrophy, cerebrotendinous xanthomatosis, Niemann-Pick type C and Wilson disease. Genetic counseling is mandatory in some X-linked diseases - ornithine transcarbamylase deficiency and adrenoleukodystrophy - and recommended in maternally inherited mitochondrial diseases - mutations of mitochondrial DNA. Besides these practical considerations, the contribution of metabolism to the field of adult neurology and neurosciences is much greater: first, with the identification of blood biomarkers that are progressively changing our diagnostic strategies thanks to lipidomic approaches, as illustrated in the field of spastic paraplegia and atypical psychiatric presentations; and second, through the understanding of pathophysiological mechanisms involved in common neurological diseases thanks to the study of these rare diseases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. A Metabolic Study of Huntington's Disease.

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    Rajasree Nambron

    Full Text Available Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III and controls.Control (n = 15, premanifest (n = 14 and stage II/III (n = 13 participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a, fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test.We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine there is a suggestion (p values between 0.02 and 0.05 that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious.Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that

  16. A Metabolic Study of Huntington's Disease.

    Science.gov (United States)

    Nambron, Rajasree; Silajdžić, Edina; Kalliolia, Eirini; Ottolenghi, Chris; Hindmarsh, Peter; Hill, Nathan R; Costelloe, Seán J; Martin, Nicholas G; Positano, Vincenzo; Watt, Hilary C; Frost, Chris; Björkqvist, Maria; Warner, Thomas T

    2016-01-01

    Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III) and controls. Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test. We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious. Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that the majority

  17. Occult Metabolic Bone Disease in Chronic Pancreatitis

    African Journals Online (AJOL)

    2017-10-26

    Oct 26, 2017 ... 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.

  18. Migraine, cerebrovascular disease and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Alexandra J Sinclair

    2012-01-01

    Full Text Available Evidence is emerging that migraine is not solely a headache disorder. Observations that ischemic stroke could occur in the setting of a migraine attack, and that migraine headaches could be precipitated by cerebral ischemia, initially highlighted a possibly association between migraine and cerebrovascular disease. More recently, large population-based studies that have demonstrated that migraineurs are at increased risk of stroke outside the setting of a migraine attack have prompted the concept that migraine and cerebrovascular disease are comorbid conditions. Explanations for this association are numerous and widely debated, particularly as the comorbid association does not appear to be confined to the cerebral circulation as cardiovascular and peripheral vascular disease also appear to be comorbid with migraine. A growing body of evidence has also suggested that migraineurs are more likely to be obese, hypertensive, hyperlipidemic and have impaired insulin sensitivity, all features of the metabolic syndrome. The comorbid association between migraine and cerebrovascular disease may consequently be explained by migraineurs having the metabolic syndrome and consequently being at increased risk of cerebrovascular disease. This review will summarise the salient evidence suggesting a comorbid association between migraine, cerebrovascular disease and the metabolic syndrome.

  19. Metabolic Syndrome: Genetic Insights into Disease Pathogenesis

    Science.gov (United States)

    Ziki, Maen D. Abou; Mani, Arya

    2016-01-01

    Purpose of review Metabolic syndrome (MetS) is a cluster of inter-related and heritable metabolic traits, which collectively impart unsurpassed risk for atherosclerotic cardiovascular disease and type 2 diabetes. Considerable work has been done to understand the underlying disease mechanisms by elucidating its genetic etiology. Recent findings Genome-wide association studies (GWAS) have been widely utilized albeit with modest success in identifying variants that are associated with more than two metabolic traits. Another limitation of this approach is the inherent small effect of the common variants, a major barrier for dissecting their cognate pathways. Modest advances in this venue have been also made by genetic studies of kindreds at the extreme ends of quantitative distributions. These efforts have led to the discovery of a number of disease genes with large effects that underlie the association of diverse traits of this syndrome. Summary Substantial progress has been made over the last decade in identification of genetic risk factors associated with the various traits of MetS. The heterogeneity and multifactorial heritability of MetS, however, has been a challenge towards understanding the factors underlying the association of these traits. Genetic investigations of outlier kindreds or homogenous populations with high prevalence for the disease can potentially improve our knowledge of the disease pathophysiology. PMID:26825138

  20. 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

  1. 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

  2. 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...

  3. 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.

  4. [Nutritional and metabolic aspects of neurological diseases].

    Science.gov (United States)

    Planas Vilà, Mercè

    2014-01-01

    The central nervous system regulates food intake, homoeostasis of glucose and electrolytes, and starts the sensations of hunger and satiety. Different nutritional factors are involved in the pathogenesis of several neurological diseases. Patients with acute neurological diseases (traumatic brain injury, cerebral vascular accident hemorrhagic or ischemic, spinal cord injuries, and cancer) and chronic neurological diseases (Alzheimer's Disease and other dementias, amyotrophic lateral sclerosis, Parkinson's Disease) increase the risk of malnutrition by multiple factors related to nutrient ingestion, abnormalities in the energy expenditure, changes in eating behavior, gastrointestinal changes, and by side effects of drugs administered. Patients with acute neurological diseases have in common the presence of hyper metabolism and hyper catabolism both associated to a period of prolonged fasting mainly for the frequent gastrointestinal complications, many times as a side effect of drugs administered. During the acute phase, spinal cord injuries presented a reduction in the energy expenditure but an increase in the nitrogen elimination. In order to correct the negative nitrogen balance increase intakes is performed with the result of a hyper alimentation that should be avoided due to the complications resulting. In patients with chronic neurological diseases and in the acute phase of cerebrovascular accident, dysphagia could be present which also affects intakes. Several chronic neurological diseases have also dementia, which lead to alterations in the eating behavior. The presence of malnutrition complicates the clinical evolution, increases muscular atrophy with higher incidence of respiratory failure and less capacity to disphagia recuperation, alters the immune response with higher rate of infections, increases the likelihood of fractures and of pressure ulcers, increases the incapacity degree and is an independent factor to increase mortality. The periodic nutritional

  5. 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...

  6. Celiac disease: A missed cause of metabolic bone disease

    Directory of Open Access Journals (Sweden)

    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.

  7. Transgenic mouse models of metabolic bone disease.

    Science.gov (United States)

    McCauley, L K

    2001-07-01

    The approach of gene-targeted animal models is likely the most important experimental tool contributing to recent advances in skeletal biology. Modifying the expression of a gene in vivo, and the analysis of the consequences of the mutation, are central to the understanding of gene function during development and physiology, and therefore to our understanding of the gene's role in disease states. Researchers had been limited to animal models primarily involving pharmaceutical manipulations and spontaneous mutations. With the advent of gene targeting, however, animal models that impact our understanding of metabolic bone disease have evolved dramatically. Interestingly, some genes that were expected to yield dramatic phenotypes in bone, such as estrogen receptor-alpha or osteopontin, proved to have subtle phenotypes, whereas other genes, such as interleukin-5 or osteoprotegerin, were initially identified as having a role in bone metabolism via the analysis of their phenotype after gene ablation or overexpression. Particularly important has been the advance in knowledge of osteoblast and osteoclast independent and dependent roles via the selective targeting of genes and the consequent disruption of bone formation, bone resorption, or both. Our understanding of interactions of the skeletal system with other systems, ie, the vascular system and homeostatic controls of adipogenesis, has evolved via animal models such as the matrix gla protein, knock-out, and the targeted overexpression of Delta FosB. Challenging transgenic models such as the osteopontin-deficient mice with mediators of bone remodeling like parathyroid hormone and mechanical stimuli and extending phenotype characterization to mechanistic in vitro studies of primary bone cells is providing additional insight into the mechanisms involved in pathologic states and their potentials for therapeutic strategies. This review segregates characterization of transgenic models based on the category of gene altered

  8. 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

  9. Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases

    DEFF Research Database (Denmark)

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

    2018-01-01

    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.......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...

  10. Metabolic Syndrome and Chronic Renal Disease

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. Metabolically healthy obesity and ischemic heart disease

    DEFF Research Database (Denmark)

    Hansen, Louise; Netterstrøm, 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...... 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...... 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. Conclusions: Being obese is associated with higher incidence of IHD irrespective of metabolic status, and we question...

  13. Metabolic syndrome and chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Anis Belarbia

    2015-01-01

    Full Text Available To determine the prevalence of metabolic syndrome (MS in chronic kidney disease (CKD patients as well as its effects on the progression of CKD, we conducted a prospective, longitudinal study including 180 patients with chronic renal failure followed at the outpatient service of Nephrology at the Saloul′s University Hospital of Sousse (Tunisia over six months. Our study population consisted of 101 men and 79 women. Chronic glomerulonephritis (36.6% was the most frequent nephropathy. The mean serum creatinine was 249 ± 200 mmol/L and the mean estimated glomerular filtration rate (eGFR was 55.8 ± 49.2 mL/min. Cardiovascular (CV impairment was found in 27.2% of the patients. The prevalence of MS was 42.2%. Women had significantly more abdominal obesity than men. Subjects with MS were significantly older and predominantly females who had higher blood pressure and body mass index (BMI. CV complications were more frequent among the MS subjects than among the controls. Glycemia, triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-c were significantly higher in the group of CKD patients with MS. However, the occurrence of MS was not influenced by the nature of nephropathy, the degree of the CKD and the use of renin-angiotensin blockers or statins. In multivariate analysis, predictors of occurrence of MS in our series included older age, female gender and higher BMI and LDL-c levels. The prevalence of MS in patients with CKD is higher than the general population. These patients should receive special multidisciplinary care to limit CV complications.

  14. Metabolic syndrome and chronic kidney disease.

    Science.gov (United States)

    Belarbia, Anis; Nouira, Safa; Sahtout, Wissal; Guedri, Yosra; Achour, Abdellatif

    2015-09-01

    To determine the prevalence of metabolic syndrome (MS) in chronic kidney disease (CKD) patients as well as its effects on the progression of CKD, we conducted a prospective, longitudinal study including 180 patients with chronic renal failure followed at the outpatient service of Nephrology at the Saloul's University Hospital of Sousse (Tunisia) over six months. Our study population consisted of 101 men and 79 women. Chronic glomerulonephritis (36.6%) was the most frequent nephropathy. The mean serum creatinine was 249 ± 200 mmol/L and the mean estimated glomerular filtration rate (eGFR) was 55.8 ± 49.2 mL/min. Cardiovascular (CV) impairment was found in 27.2% of the patients. The prevalence of MS was 42.2%. Women had significantly more abdominal obesity than men. Subjects with MS were significantly older and predominantly females who had higher blood pressure and body mass index (BMI). CV complications were more frequent among the MS subjects than among the controls. Glycemia, triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-c) were significantly higher in the group of CKD patients with MS. However, the occurrence of MS was not influenced by the nature of nephropathy, the degree of the CKD and the use of renin-angiotensin blockers or statins. In multivariate analysis, predictors of occurrence of MS in our series included older age, female gender and higher BMI and LDL-c levels. The prevalence of MS in patients with CKD is higher than the general population. These patients should receive special multidisciplinary care to limit CV complications.

  15. Host–Microbiota Mutualism in Metabolic Diseases

    Directory of Open Access Journals (Sweden)

    Salvatore Fabbiano

    2017-10-01

    Full Text Available The intestinal microbiota is a plastic ecosystem that is shaped by environmental and genetic factors, interacting with virtually all tissues of the host. Many signals result from the interplay between the microbiota with its mammalian symbiont that can lead to altered metabolism. Disruptions in the microbial composition are associated with a number of comorbidities linked to the metabolic syndrome. Promoting the niche expansion of beneficial bacteria through diet and supplements can improve metabolic disorders. Reintroducing bacteria through probiotic treatment or fecal transplant is a strategy under active investigation for multiple pathological conditions. Here, we review the recent knowledge of microbiota’s contribution to host pathology, the modulation of the microbiota by dietary habits, and the potential therapeutic benefits of reshaping the gut bacterial landscape in context of metabolic disorders such as obesity.

  16. Host–Microbiota Mutualism in Metabolic Diseases

    Science.gov (United States)

    Fabbiano, Salvatore; Suárez-Zamorano, Nicolas; Trajkovski, Mirko

    2017-01-01

    The intestinal microbiota is a plastic ecosystem that is shaped by environmental and genetic factors, interacting with virtually all tissues of the host. Many signals result from the interplay between the microbiota with its mammalian symbiont that can lead to altered metabolism. Disruptions in the microbial composition are associated with a number of comorbidities linked to the metabolic syndrome. Promoting the niche expansion of beneficial bacteria through diet and supplements can improve metabolic disorders. Reintroducing bacteria through probiotic treatment or fecal transplant is a strategy under active investigation for multiple pathological conditions. Here, we review the recent knowledge of microbiota’s contribution to host pathology, the modulation of the microbiota by dietary habits, and the potential therapeutic benefits of reshaping the gut bacterial landscape in context of metabolic disorders such as obesity. PMID:29056925

  17. Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: an overview.

    NARCIS (Netherlands)

    Castro, R.; Rivera, I.; Blom, H.J.; Jakobs, C.; Almeida, I.T. de

    2006-01-01

    Hyperhomocysteinaemia has been regarded as a new modifiable risk factor for atherosclerosis and vascular disease. Homocysteine is a branch-point intermediate of methionine metabolism, which can be further metabolised via two alternative pathways: degraded irreversibly through the transsulphuration

  18. 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 (PET...

  19. Disturbed tryptophan metabolism in cardiovascular disease.

    Science.gov (United States)

    Mangge, H; Stelzer, I; Reininghaus, E Z; Weghuber, D; Postolache, T T; Fuchs, D

    2014-06-01

    cardiovascular morbidity and mortality. Accelerated catabolism of TRP is further involved in the pathogenesis of the anemia of scLGI. The pro-inflammatory cytokine IFN-γ suppresses growth and differentiation of erythroid progenitor cells, and the depletion of TRP limits protein synthesis and thus hemoglobin production, and, through reduction in oxygen supply, may contribute to ischemic vascular disease. In this review we discuss the impact of TRP breakdown and the related complex mechanisms on the prognosis and individual course of CVD. Measurement of TRP, KYN concentrations, and calculation of the KYN/TRYP ratio will contribute to a better understanding of the interplay between inflammation, metabolic syndrome, mood disturbance, and anemia, all previously described as significant predictors of an unfavorable outcome in patients with CVD. The review leads to a novel framework for successful therapeutic modification of several cardinal pathophysiological processes leading to adverse cardiovascular outcome.

  20. 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.

  1. The metabolic syndrome and vascular disease

    NARCIS (Netherlands)

    Olijhoek, Jobien Karen

    2006-01-01

    In the Western population cardiovascular diseases are the most common cause of mortality and morbidity. There are several important risk factors for cardiovascular diseases, among them hypertension, hypercholesterolemia, diabetes and obesity. The clustering of cardiovascular risk factors associated

  2. [Gut microbiota and immune crosstalk in metabolic disease].

    Science.gov (United States)

    Burcelin, Rémy

    2017-01-01

    The aim of the review is to discuss about the role played by the defence crosstalk between the gut microbiota and the intestinal immune system, in the development of metabolic disease focusing on obesity and diabetes. Starting from physiological and pathological stand points and based on the latest published data, this review is addressing how the concept of the hologenome theory of evolution can drive the fate of metabolic disease. The notion of "metabolic infection" to explain the "metabolic inflammation" is discussed. This imply comments about the process of bacterial translocation and impaired intestinal immune defense against commensals. Eventually this review sets the soil for personalized medicine. The monthly increase in the number of publications on the gut microbiota to intestinal immune defense and the control of metabolism demonstrate the importance of this field of investigation. The notion of commensal as "self or non-self" has to be reevaluated in the light of the current data. Furthermore, data demonstrate the major role played by short chain fatty acids, secondary bile acids, LPS, peptidoglycans, indole derivatives, and other bacteria-related molecules on the shaping of cells involved in the intestinal protection against commensals is now becoming a central player in the incidence of metabolic diseases. The literature demonstrates that the onset of metabolic diseases and some specific co-morbidities can be explained by a gut microbiota to intestinal immune system crosstalk. Therefore, one should now consider this avenue of investigation as a putative source of biomarkers and therapeutic targets to personalize the treatment of metabolic disease and its co-morbidities. Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. A clinical perspective of obesity, metabolic syndrome and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    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.

  6. Metabolic syndrome, chronic kidney, and cardiovascular diseases: role of adipokines.

    Science.gov (United States)

    Tesauro, Manfredi; Canale, Maria Paola; Rodia, Giuseppe; Di Daniele, Nicola; Lauro, Davide; Scuteri, Angelo; Cardillo, Carmine

    2011-03-07

    Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS) leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD). Albuminuria is a major risk factor for cardiovascular diseases (CVDs). Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.

  7. Metabolic Syndrome, Chronic Kidney, and Cardiovascular Diseases: Role of Adipokines

    Directory of Open Access Journals (Sweden)

    Manfredi Tesauro

    2011-01-01

    Full Text Available Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD. Albuminuria is a major risk factor for cardiovascular diseases (CVDs. Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.

  8. Latest data on metabolic diseases: Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Angelidi Angeliki

    2017-01-01

    Full Text Available Hypertension is closely related with increased cardiovascular risk and renal damage and its prevalence is even greater in elderly patients that are a highly heterogeneous group. The identification of hypertensive patients, as well as prompt initiation and timely titration of pharmacologic therapy in addition to lifestyle therapy in order to achieve blood pressure goals is of paramount importance. In general population, blood pressure goals of <140/90mmHg are recommended. However, treatment strategies and pharmacological therapy should be personalized depending on patient characteristics and comorbidities. Some drug agents or combinations should be considered as the preferential choice in specific conditions. However, the combination of two antagonists of the Renin Angiotensin System (RAS is not recommended and should be discouraged. In elderly hypertensives, it is recommended to reduce Systolic Blood Pressure (SBP between 150 and 140mmHg, provided they are in good physical and mental conditions, while a target of SBP <140mmHg may be considered, if treatment is also well tolerated. Lifestyle changes, and particularly weight loss and physical exercise, are to be recommended to all individuals with the metabolic syndrome. These interventions improve not only blood pressure, but the metabolic components of the syndrome. Antihypertensive agents that potentially improve or at least not worsen insulin sensitivity, such as RAS blockers and calcium antagonists, should be considered as the preferred drugs. Regarding patients with diabetes, lifestyle therapy and blood pressure goals of <140/90mmHg is generally recommended (American Diabetes Association, 2017. An ACE inhibitor or angiotensin receptor blocker, at the maximum tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for hypertension in patients with diabetes and albuminuria. Taking into account several studies and meta-analyses recently published

  9. Gut microbiota and immune crosstalk in metabolic disease.

    Science.gov (United States)

    Burcelin, Rémy

    2016-09-01

    Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes, and hepatic steatosis, the mechanisms causal to the disease could be related to the translocation of microbiota from the gut to the tissues, inducing inflammation. The mechanisms regulating such a process are based on the crosstalk between the gut microbiota and the host immune system. The hologenome theory of evolution supports this concept and implies that therapeutic strategies aiming to control glycemia should take into account both the gut microbiota and the host immune system. This review discusses the latest evidence regarding the bidirectional impact of the gut microbiota on host immune system crosstalk for the control of metabolic disease, hyperglycemia, and obesity. To avoid redundancies with the literature, we will focus our attention on the intestinal immune system, identifying evidence for the generation of novel therapeutic strategies, which could be based on the control of the translocation of gut bacteria to tissues. Such novel strategies should hamper the role played by gut microbiota dysbiosis on the development of metabolic inflammation. Recent evidence in rodents allows us to conclude that an impaired intestinal immune system characterizes and could be causal in the development of metabolic disease. The fine understanding of the molecular mechanisms should allow for the development of a first line of treatment for metabolic disease and its co-morbidities. This article is part of a special issue on microbiota.

  10. Skeletal scintigraphy and quantitative tracer studies in metabolic bone disease

    Science.gov (United States)

    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

  11. Endoplasmic reticulum-mitochondria calcium signaling in hepatic metabolic diseases.

    Science.gov (United States)

    Rieusset, Jennifer

    2017-06-01

    The liver plays a central role in glucose homeostasis, and both metabolic inflexibility and insulin resistance predispose to the development of hepatic metabolic diseases. Mitochondria and endoplasmic reticulum (ER), which play a key role in the control of hepatic metabolism, also interact at contact points defined as mitochondria-associated membranes (MAM), in order to exchange metabolites and calcium (Ca 2+ ) and regulate cellular homeostasis and signaling. Here, we overview the role of the liver in the control of glucose homeostasis, mainly focusing on the independent involvement of mitochondria, ER and Ca 2+ signaling in both healthy and pathological contexts. Then we focus on recent data highlighting MAM as important hubs for hormone and nutrient signaling in the liver, thus adapting mitochondria physiology and cellular metabolism to energy availability. Lastly, we discuss how chronic ER-mitochondria miscommunication could participate to hepatic metabolic diseases, pointing MAM interface as a potential therapeutic target for metabolic disorders. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Metabolism-Centric Overview of the Pathogenesis of Alzheimer's Disease.

    Science.gov (United States)

    Kang, Somang; Lee, Yong Ho; Lee, Jong Eun

    2017-05-01

    Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia. AD is characterized by the extracellular amyloid beta (Aβ) plaques and intraneuronal deposits of neurofibrillary tangles (NFTs). Recently, as aging has become a familiar phenomenon around the world, patients with AD are increasing in number. Thus, many researchers are working toward finding effective therapeutics for AD focused on Aβ hypothesis, although there has been no success yet. In this review paper, we suggest that AD is a metabolic disease and that we should focus on metabolites that are affected by metabolic alterations to find effective therapeutics for AD. Aging is associated with not only AD but also obesity and type 2 diabetes (T2DM). AD, obesity, and T2DM share demographic profiles, risk factors, and clinical and biochemical features in common. Considering AD as a kind of metabolic disease, we suggest insulin, adiponectin, and antioxidants as mechanistic links among these diseases and targets for AD therapeutics. Patients with AD show reduced insulin signal transductions in the brain, and intranasal injection of insulin has been found to have an effect on AD treatment. In addition, adiponectin is decreased in the patients with obesity and T2DM. This reduction induces metabolic dysfunction both in the body and the brain, leading to AD pathogenesis. Oxidative stress is known to be induced by Aβ and NFTs, and we suggest that oxidative stress caused by metabolic alterations in the body induce brain metabolic alterations, resulting in AD. © Copyright: Yonsei University College of Medicine 2017.

  13. The gut microbiota and metabolic disease

    DEFF Research Database (Denmark)

    Arora, T; Bäckhed, Gert Fredrik

    2016-01-01

    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 e......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......-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...

  14. Transferrin metabolism in alcoholic liver disease

    International Nuclear Information System (INIS)

    Potter, B.J.; Chapman, R.W.; Nunes, R.M.; Sorrentino, D.; Sherlock, S.

    1985-01-01

    The metabolism of transferrin was studied using purified 125 I-labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group. There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 +/- 0.3 gm per liter vs. 2.9 +/- 0.2; p less than 0.01), resulting from diminished total body synthesis (0.9 +/- 0.2 mg per kg per hr vs. 1.8 +/- 0.2; p less than 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 +/- 0.3 mg per kg per hr) was significantly increased when compared with controls (p less than 0.05). For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = +0.70; p less than 0.01) but the serum iron did not. These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerated

  15. 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.

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

    Science.gov (United States)

    2017-06-27

    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

  17. [Review on periodontal disease and metabolic control of diabetes mellitus].

    Science.gov (United States)

    Steffens, João Paulo; Glaci Reinke, Stella Maria; Angel Muñoz, Miguel; Santos, Fábio André dos; Luiz Pilatti, Gibson

    2010-09-01

    There may be an interaction between periodontal disease and some systemic diseases such as diabetes mellitus. The objective of this review was to verify, by means of a review of clinical trials, if there is a positive association between periodontal disease and the glycemic control of type 2 diabetes mellitus (DM-2) patients. Eleven articles that fi t the study criteria were revised. It was concluded that periodontal disease may influence the metabolic control of DM-2. Additional studies with larger sample sizes and longer follow up are necessary for a better clarification of this issue.

  18. Latest data on metabolic diseases: Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Panagiota Mitrou

    2017-01-01

    Full Text Available With such a high cost in money and human lives, diabetes mellitus (DM is a major challenge for health care systems and an obstacle to sustainable economic growth. The pathophysiological disorders of diabetes include, besides the defect in pancreatic insulin secretion and insulin resistance in peripheral tissues (liver, muscle and adipose tissue, increased lipolysis, increased glucagon secretion, impaired secretion and action of incretin hormones, increased glucose resorption by the kidney and defects in the central nervous system. The therapeutic intervention must be timely and personalized. Lifestyle interventions (diet, exercise, smoking cessation are the cornerstone of treatment. Treatment should begin with metformin unless there is a contraindication (eg renal failure or intolerance (eg, gastrointestinal disorders. If HbA1c remains off target a second or a third treatment may be added, orally (glitazone, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylurea or by injection (GLP-1 agonist or basal insulin. On failure to achieve glycemic target combinations of injectable treatments (combination of agonist GLP-1 with basal insulin, intensified insulin therapy or in some cases insulin mixtures are recommended. New treatments (weekly administered GLP-1 analogs, combination of a basal insulin / GLP-1 in one injection, SGLT-2 inhibitors, long acting basal insulins in combination with the old tried treatments (e.g. metformin, pioglitazone, inhibitors DPP-4 can contribute to human-centered and individualized management of patients with diabetes. The cardiovascular safety of antidiabetic treatment should be considered. There is a need for early diagnosis and treatment of glucose metabolism disorders during pregnancy (before 24 to 28 weeks of gestation in women at high risk for developing gestational diabetes.

  19. Metabolomics reveals metabolic biomarkers of Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. 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...

  1. Peripheral modulation of the endocannabinoid system in metabolic disease.

    Science.gov (United States)

    Shrestha, Nirajan; Cuffe, James S M; Hutchinson, Dana S; Headrick, John P; Perkins, Anthony V; McAinch, Andrew J; Hryciw, Deanne H

    2018-03-01

    Dysfunction of the endocannabinoid system (ECS) has been identified in metabolic disease. Cannabinoid receptor 1 (CB 1 ) is abundantly expressed in the brain but also expressed in the periphery. Cannabinoid receptor 2 (CB 2 ) is more abundant in the periphery, including the immune cells. In obesity, global antagonism of overexpressed CB 1 reduces bodyweight but leads to centrally mediated adverse psychological outcomes. Emerging research in isolated cultured cells or tissues has demonstrated that targeting the endocannabinoid system in the periphery alleviates the pathologies associated with metabolic disease. Further, peripheral specific cannabinoid ligands can reverse aspects of the metabolic phenotype. This Keynote review will focus on current research on the functionality of peripheral modulation of the ECS for the treatment of obesity. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  2. Metaflammation, NLRP3 Inflammasome Obesity and Metabolic Disease

    Directory of Open Access Journals (Sweden)

    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

  3. Metaflammation, NLRP3 Inflammasome Obesity and Metabolic Disease

    OpenAIRE

    Anna Meiliana; Andi Wijaya

    2011-01-01

    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 hom...

  4. INFORMATION SYSTEM FOR REGISTRY OF PATIENTS WITH METABOLIC DISEASES

    Directory of Open Access Journals (Sweden)

    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.”

  5. Disturbed lipid metabolism in glycogen storage disease type 1

    NARCIS (Netherlands)

    Bandsma, RHJ; Smit, GPA; Kuipers, F

    2002-01-01

    Glycogen storage disease type 1 (GSD1) is an inborn error of metabolism caused by deficiency of glucose-6-phosphatase, the enzyme catalysing the conversion of glucose-6-phosphate (G6P) to glucose. GSD1 is associated with severe hyperlipidaemia and hepatic steatosis. The underlying mechanisms

  6. 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

  7. 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: ...

  8. Dietary Fiber, Microbiota and Obesity Related Metabolic Diseases

    Science.gov (United States)

    The presentation summarizes our research over the past 7 years on viscous soluble dietary fibers in animal models of obesity and metabolic diseases. We found that in addition to the well known cholesterol and glucose lowering ability of soluble fibers, viscous dietary fibers also prevent most of th...

  9. [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

  10. 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

  11. 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)

  12. Metabolic syndrome in inflammatory rheumatic diseases

    Directory of Open Access Journals (Sweden)

    G. La Montagna

    2011-09-01

    Full Text Available Toward the end of the last century a better knowledge of cardiovascular (CV risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called “metabolic” or “insulin resistance syndrome”. Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO and by The Third Report of The National Cholesterol Education Program’s Adult Treatment Panel (NCEP-ATP III. In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.

  13. Inherited metabolic liver diseases in infants and children: an overview

    Directory of Open Access Journals (Sweden)

    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

  14. 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

  15. 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.

  16. 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

  17. 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)

  18. Diabetes mellitus related bone metabolism and periodontal disease.

    Science.gov (United States)

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-06-26

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.

  19. Diabetes mellitus related bone metabolism and periodontal disease

    Science.gov (United States)

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts. PMID:25857702

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

    Science.gov (United States)

    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

  1. [Is the metabolic syndrome a new childhood disease?].

    Science.gov (United States)

    Janner, M; Mullis, P E; Flück, C E

    2006-03-29

    Overweight and obesity in children and adolescents have become a major public health problem in recent years throughout the world. The medical consequences of obesity may manifest as an increase in the prevalence of the metabolic syndrome in children and adolescents putting them at increased risk for future cardiovascular diseases. Obesity can cause insulin resistance and might disturb glucose homeostasis eventually leading to type 2 diabetes in susceptible patients. Insulin resistance is also involved in the pathogenesis of dyslipidemia in obese children characteristically presenting as hypertriglyceridemia and low HDL cholesterol. Even elevated blood pressure might be present in obese kids. Here we present a 12-year-old boy diagnosed with the metabolic syndrome. The diagnostic criteria of the metabolic syndrome in children and adolescents are discussed. Thoughts about pathophysiology and therapeutic options are offered.

  2. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

    International Nuclear Information System (INIS)

    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

  3. Resistant starches for the management of metabolic diseases.

    Science.gov (United States)

    Bindels, Laure B; Walter, Jens; Ramer-Tait, Amanda E

    2015-11-01

    Recent clinical trials and animal studies indicate that resistant starches may be beneficial therapeutic tools for the management of metabolic diseases. The purpose of this review is to summarize these findings and discuss the established and proposed mechanisms by which resistant starches exert their benefits. We also examine open questions regarding how resistant starches improve metabolism and propose future research directions for the field. Data from both humans and animal models clearly support a role for resistant starches in improving a variety of metabolic features; however, discrepancies do exist regarding specific effects. Concomitant improvements in both insulin levels and body fat depots are often reported in rodents fed resistant starches, whereas resistant starch feeding in humans improves insulin sensitivity without having a major impact on fat mass. These differences could be explained by the coexistence of several mechanisms (both gut microbiota-dependent and gut microbiota-independent) underpinning the metabolic benefits of resistant starches. Together, the studies presented in this review offer new insights into the potential pathways by which resistant starches enhance metabolic health, including modulation of the gut microbiota, gut peptides, circulating inflammatory mediators, innate immune cells, and the bile acid cycle.

  4. 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.

  5. 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.

  6. 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.

  7. Apolipoprotein M in lipid metabolism and cardiometabolic diseases

    DEFF Research Database (Denmark)

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

    2015-01-01

    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......: 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...

  8. 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...... analysis employed. The present review gives a comprehensive summary of the perfusion and metabolism literature in the field of PD research, including quantitative PET studies, normalized PET and SPECT studies, autoradiography studies in animal models of PD, and simulation studies of PD 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...

  9. and overnutrition and evidence of metabolic disease risk in rural ...

    African Journals Online (AJOL)

    2013-09-10

    Sep 10, 2013 ... Original Research: Under- and overnutrition and evidence of metabolic disease risk. 2014;27(4). S Afr J Clin Nutr of > 2.59 mmol/l, TGs of ≥ 1.7 mmol/l and total cholesterol (TC) of. > 5.17 mmol/l.5,23,24 Pre-hypertension was defined as the average of the last two readings of SBP or DBP, being ≥ 90th but ...

  10. 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.

  11. The association of serum leptin levels with metabolic diseases

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

    Directory of Open Access Journals (Sweden)

    Gertjan eVan Dijk

    2015-05-01

    Full Text Available Alzheimer’s disease (AD is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP to amyloid β peptide, tau protein hyperphosphorylation, relocalization and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by systems biology approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework.

  16. Metabolic cancer biology: structural-based analysis of cancer as a metabolic disease, new sights and opportunities for disease treatment.

    Science.gov (United States)

    Masoudi-Nejad, Ali; Asgari, Yazdan

    2015-02-01

    The cancer cell metabolism or the Warburg effect discovery goes back to 1924 when, for the first time Otto Warburg observed, in contrast to the normal cells, cancer cells have different metabolism. With the initiation of high throughput technologies and computational systems biology, cancer cell metabolism renaissances and many attempts were performed to revise the Warburg effect. The development of experimental and analytical tools which generate high-throughput biological data including lots of information could lead to application of computational models in biological discovery and clinical medicine especially for cancer. Due to the recent availability of tissue-specific reconstructed models, new opportunities in studying metabolic alteration in various kinds of cancers open up. Structural approaches at genome-scale levels seem to be suitable for developing diagnostic and prognostic molecular signatures, as well as in identifying new drug targets. In this review, we have considered these recent advances in structural-based analysis of cancer as a metabolic disease view. Two different structural approaches have been described here: topological and constraint-based methods. The ultimate goal of this type of systems analysis is not only the discovery of novel drug targets but also the development of new systems-based therapy strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. 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.

  18. [End stage of chronic kidney disease and metabolic acidosis].

    Science.gov (United States)

    Klaboch, J; Opatrná, S; Matoušovic, K; Schück, O

    2012-01-01

    Renal function disorder is inevitably associated with metabolic acidosis. An adult produces approximately 1 mmol of acids/kg of body weight every day (3 mmol/kg in children), derived from metabolization of proteins from food. Development of metabolic acidosis in patients with kidney disease is based on accumulation of acids and insufficient production of bicarbonates; alkaline loss represents a marginal issue here limited to patients with type II renal tubular acidosis only. The prevalence of this disorder increases with declining glomerular filtration (GFR) from 2% in patients with GFR 1.0-1.5 ml/s/1.73 m2 to 39% in patients with GFR ammoniac production in residual nephrons. This is an adaptive mechanism aimed at maintaining sufficient elimination of acids despite reduced volume of functional tissue. However, an increased ammoniac production simultaneously becomes a stimulus for activation of the complement via an alternative route and is thus one of the factors contributing, through this induced inflammation, to progression of tubular interstitial fibrosis that subsequently leads to further GFR reduction. Metabolic acidosis has a number of severe adverse effects on the organism, e.g. deterioration of kidney bone disease through stimulation of bone resorption and inhibition of bone formation, inhibition of vitamin D formation, increased muscle catabolism, reduced albumin production, glucose metabolism disorder, increased insulin resistance, reduced production of thyroid hormones, increased accumulation of β2-microglobulin etc. Non-interventional studies suggest that alkali supplementation may slow down progression of chronic nephropathies. However, this approach, safe and inexpensive, has not been widely implemented in clinical practice yet. With respect to dialyzed patients, abnormal levels of bicarbonates are associated with increased mortality. Both metabolic acidosis and alkalosis, rather regularly seen in a considerable number of patients, have a negative

  19. Dietary fats and membrane function: implications for metabolism and disease.

    Science.gov (United States)

    Hulbert, A J; Turner, N; Storlien, L H; Else, P L

    2005-02-01

    Lipids play varied and critical roles in metabolism, with function dramatically modulated by the individual fatty acid moities in complex lipid entities. In particular, the fatty acid composition of membrane lipids greatly influences membrane function. Here we consider the role of dietary fatty acid profile on membrane composition and, in turn, its impact on prevalent disease clusters of the metabolic syndrome and mental illness. Applying the classical physiological conformer-regulator paradigm to quantify the influence of dietary fats on membrane lipid composition (i.e. where the membrane variable is plotted against the same variable in the environment--in this case dietary fats), membrane lipid composition appears as a predominantly regulated parameter. Membranes remain relatively constant in their saturated (SFA) and monounsaturated (MUFA) fatty acid levels over a wide range of dietary variation for these fatty acids. Membrane composition was found to be more responsive to n-6 and n-3 polyunsaturated fatty acid (PUFA) levels in the diet and most sensitive to n-3 PUFA and to the n-3/n-6 ratio. These differential responses are probably due to the fact that both n-6 and n-3 PUFA classes cannot be synthesised de novo by higher animals. Diet-induced modifications in membrane lipid composition are associated with changes in the rates of membrane-linked cellular processes that are major contributors to energy metabolism. For example, in the intrinsic activity of fundamental processes such as the Na+/K+ pump and proton pump-leak cycle. Equally, dietary lipid profile impacts substantially on diseases of the metabolic syndrome with evidence accruing for changes in metabolic rate and neuropeptide regulation (thus influencing both sides of the energy balance equation), in second messenger generation and in gene expression influencing a range of glucose and lipid handling pathways. Finally, there is a growing literature relating changes in dietary fatty acid profile to many

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

    Science.gov (United States)

    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."

  1. 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.

  2. 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.

  3. Black leaf streak disease affects starch metabolism in banana fruit.

    Science.gov (United States)

    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.

  4. The emerging use of zebrafish to model metabolic disease

    Directory of Open Access Journals (Sweden)

    Asha Seth

    2013-09-01

    Full Text Available The zebrafish research community is celebrating! The zebrafish genome has recently been sequenced, the Zebrafish Mutation Project (launched by the Wellcome Trust Sanger Institute has published the results of its first large-scale ethylnitrosourea (ENU mutagenesis screen, and a host of new techniques, such as the genome editing technologies TALEN and CRISPR-Cas, are enabling specific mutations to be created in model organisms and investigated in vivo. The zebrafish truly seems to be coming of age. These powerful resources invoke the question of whether zebrafish can be increasingly used to model human disease, particularly common, chronic diseases of metabolism such as obesity and type 2 diabetes. In recent years, there has been considerable success, mainly from genomic approaches, in identifying genetic variants that are associated with these conditions in humans; however, mechanistic insights into the role of implicated disease loci are lacking. In this Review, we highlight some of the advantages and disadvantages of zebrafish to address the organism’s utility as a model system for human metabolic diseases.

  5. Influence of vitamin D in endocrine metabolic diseases

    Directory of Open Access Journals (Sweden)

    Rafael Algusto Rafaelli

    2015-05-01

    Full Text Available The vitamin D deficiency has been linked to the development of several endocrine metabolic diseases such as metabolic syndrome, obesity, hypertension and Type 2 diabetes mellitus. This paper presents an overview of the available scientific evidence for some of the non- calcemic actions of vitamin D in humans, through literature search in scientific databases. The deficiency of vitamin D may predispose to glucose intolerance, changes in insulin secretion and thus the development of type 2 diabetes mellitus. This mechanism is possible due to the presence of the vitamin D receptor in several tissues and cells, including pancreatic ? cells, adipocyte and muscle tissue. In obese individuals, the changes of the vitamin D endocrine system, characterized by high levels of parathyroid hormone and 1,25-dihydroxycholecalciferol are responsible for the negative feedback of hepatic synthesis of 25-hydroxycholecalciferol and also by increased influx of calcium into the intracellular environment, which can damage the secretion and insulin sensitivity. In hypertension, vitamin D could act on the renin-angiotensin system and also in vascular function. There is some evidence that 1,25-dihydroxycholecalciferol inhibits the renin gene expression and blocks the proliferation of vascular smooth muscle cell. Further prospective studies and randomized clinical trials, including studies of supplementation, are required to establish better clinical and metabolic effects of variations in the concentration of 25-hydroxycholecalciferol in the clinical course of these diseases.

  6. Bisphenol A sulfonation is impaired in metabolic and liver disease.

    Science.gov (United States)

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

    2016-02-01

    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. To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. 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. 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. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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)

  8. Genetic Manipulations of PPARs: Effects on Obesity and Metabolic Disease

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. Bone mineral content measurement in metabolic bone disease

    Energy Technology Data Exchange (ETDEWEB)

    Shapiro, B.; Fig, L.M.; Gross, M.D.

    1987-02-01

    Objective determinations of bone mineral content (BMC) are seldom required for the diagnosis of the metabolic and hormonal disorders which may result in osteoporosis. They are, however, required to document the osteoporosis itself as this is usually subclinical until late in the natural history of the disease process. Measurement of BMC in these disease processes is an important research tool in determining the effect of the disorder on the skeleton at different stages of the natural history and in investigating the effects of therapy and other interventions. Measurements of BMC may be useful in clinical practice in deciding whether to intervene in certain circumstances (e.g. asymptomatic hyperparathyroidism) or to withhold certain therapies (e.g. glucocorticoids) or to alter therapy (e.g. change from glucocorticoids to nonsteroidal immunosuppressives in autoimmune diseases). It may also play a role in monitoring the responses to therapeutic interventions.

  11. Carotid body, insulin and metabolic diseases: unravelling the links

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. Understanding the causes and implications of endothelial metabolic variation in cardiovascular disease through genome scale metabolic modeling

    Directory of Open Access Journals (Sweden)

    Sarah eMcGarrity

    2016-04-01

    Full Text Available High-throughput biochemical profiling has led to a requirement for advanced data interpretation techniques capable of integrating the analysis of gene, protein, and metabolic profiles to shed light on genotype-phenotype relationships. Herein, we consider the current state of knowledge of endothelial cell (EC metabolism and its connections to cardiovascular disease, and explore the use of genome scale metabolic models (GEMs for integrating metabolic and genomic data. GEMs combine gene expression and metabolic data acting as frameworks for their analysis and, ultimately, afford mechanistic understanding of how genetic variation impacts metabolism. We demonstrate how GEMs can be used to investigate cardiovascular disease-related genetic variation, drug resistance mechanisms, and novel metabolic pathways, in ECs. The application of GEMs in personalized medicine is also highlighted. Particularly, we focus on the potential of GEMs to identify metabolic biomarkers of endothelial dysfunction and to discover methods of stratifying treatments for cardiovascular diseases based on individual genetic markers. Recent advances in systems biology methodology, and how these methodologies can be applied to understand EC metabolism in both health and disease, are thus highlighted.

  14. Endocrine manifestations related to inherited metabolic diseases in adults

    Directory of Open Access Journals (Sweden)

    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.

  15. Primary endoscopic therapies for obesity and metabolic diseases.

    Science.gov (United States)

    Kumbhari, Vivek; Oberbach, Andreas; Nimgaonkar, Ashish

    2015-09-01

    Endoscopic approaches to obesity may help fulfill the unmet need of over half the US adult population who would benefit from therapy for obesity but are not receiving it. Endoluminal approaches have the potential to be more efficacious than antiobesity medications and have a lower risk-cost profile compared with bariatric surgery. This review outlines the current state of primary endoscopic weight loss and metabolic therapies and sheds light on the challenges faced toward making endoscopic bariatric therapies 'ready for prime time'. Endoscopic approaches to obesity are being increasingly modeled on the proposed mechanisms contributing to the benefits of bariatric surgery.Therapies targeted at the stomach induce weight loss with only a proportional benefit to underlying metabolic disorders.Therapies targeting the proximal small bowel appear to modulate various neurohormonal pathways resulting in an improvement in metabolic profile in excess to that accounted for by weight loss itself. Rigorous scientific assessment of endoscopic approaches to obesity is necessary to allow its integration into the treatment algorithm of obesity. The endoscopic armamentarium against obesity continues to evolve with the endoscopist poised to be a key player in the management of this disease. http://links.lww.com/COG/A12.

  16. Pathophysiology and therapeutics of cardiovascular disease in metabolic syndrome.

    Science.gov (United States)

    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.

  17. 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.

  18. Dysregulated adipokine metabolism in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Breyer, Marie-Kathrin; Rutten, Erica P A; Locantore, Nicholas W; Watkins, Michael L; Miller, Bruce E; Wouters, Emiel F M

    2012-09-01

    Research concerning the involvement of body composition and systemic inflammatory markers in adipokine metabolism in chronic obstructive pulmonary disease (COPD) is still limited. Therefore, we primarily aimed to investigate the adipokine metabolism in relation to these systemic inflammatory biomarkers and to evaluate possible gender-related differences in the adipokine metabolism in patients with COPD. One hundred and eighty-six subjects with COPD [mean (SD) FEV(1) %pred: 50 (±16)] and 113 controls, matched for age, gender and body composition were selected from the ECLIPSE cohort. The following serological data were collected: serum levels of leptin, adiponectin and systemic inflammatory biomarkers such as C-reactive protein (CRP), Interleukin-6 (IL-6) and fibrinogen. Compared with controls, patients with COPD had higher levels of CRP, IL-6, fibrinogen and adiponectin. After stratification for gender, men with COPD had higher CRP, IL6 and fibrinogen levels compared with male controls, while women with COPD had higher levels of CRP and fibrinogen compared with the female controls. Moreover, in both female controls and patients with COPD, leptin correlated with CRP and fibrinogen, while leptin only correlated with CRP in male controls. Adiponectin correlated negatively with CRP, only in patients with COPD. Body mass index and gender were the strongest determinants for both leptin and adiponectin. This study shows a gender-dependent dysregulation of adipokine metabolism in patients with COPD compared with BMI-matched controls. Furthermore, results from this study suggest a more prominent role of adiponectin in the systemic response to COPD. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

  19. Metabolic Networks Underlying Cognitive Reserve in Prodromal Alzheimer Disease: A European Alzheimer Disease Consortium Project

    NARCIS (Netherlands)

    Morbelli, S.; Perneczky, R.; Drzezga, A.; Frisoni, G. B.; Caroli, A.; van Berckel, B.N.M.; Ossenkoppele, R.; Guedj, E.; Didic, M.; Brugnolo, A.; Naseri, M.; Sambuceti, G.; Pagani, M.; Nobili, F.

    2013-01-01

    This project aimed to investigate the metabolic basis for resilience to neurodegeneration (cognitive reserve) in highly educated patients with prodromal Alzheimer disease (AD). Methods: Sixty-four patients with amnestic mild cognitive impairment who later converted to AD dementia during follow-up,

  20. 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.

  1. Epicardial adipose tissue in endocrine and metabolic diseases.

    Science.gov (United States)

    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.

  2. 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

  3. Can We Prevent Obesity-Related Metabolic Diseases by Dietary Modulation of the Gut Microbiota?1

    Science.gov (United States)

    2016-01-01

    Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity-related metabolic diseases and the potential of dietary modulation of the gut microbiota in metabolic disease prevention and treatment. PMID:26773017

  4. 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.)

  5. 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

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

    Science.gov (United States)

    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.

  7. Inherent lipid metabolic dysfunction in glycogen storage disease IIIa.

    Science.gov (United States)

    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.

  8. Prevalence of chronic kidney disease in adults with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. 4-Hydroxynonenal (HNE) modified proteins in metabolic diseases.

    Science.gov (United States)

    Castro, José Pedro; Jung, Tobias; Grune, Tilman; Siems, Werner

    2017-10-01

    4-Hydroxynonenal (HNE) is one of the quantitatively most important products of lipid peroxidation. Due to its high toxicity it is quickly metabolized, however, a small share of HNE avoids enzymatic detoxification and reacts with biomolecules including proteins. The formation of HNE-protein-adducts is one of the accompanying processes in oxidative stress or redox disbalance. The modification of proteins might occur at several amino acids side chains, leading to a variety of products and having effects on the protein function and fate. This review summarizes current knowledge on the formation of HNE-modified proteins, their fate in mammalian cells and their potential role as a damaging agents during oxidative stress. Furthermore, the potential of HNE-modified proteins as biomarkers for several diseases are highlighted. Copyright © 2016. Published by Elsevier Inc.

  11. Hepcidin: an important iron metabolism regulator in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Sandra Azevedo Antunes

    Full Text Available Abstract Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production. The elevation of hepcidin has been associated with infection, inflammation, atherosclerosis, insulin resistance and oxidative stress. Some strategies were tested to reduce the effects of hepcidin in patients with CKD, however more studies are necessary to assess the impact of its modulation in the management of anemia in this population.

  12. Resting metabolic connectivity in prodromal Alzheimer's disease. A European Alzheimer Disease Consortium (EADC) project.

    Science.gov (United States)

    Morbelli, Silvia; Drzezga, Alex; Perneczky, Robert; Frisoni, Giovanni B; Caroli, Anna; van Berckel, Bart N M; Ossenkoppele, Rik; Guedj, Eric; Didic, Mira; Brugnolo, Andrea; Sambuceti, Gianmario; Pagani, Marco; Salmon, Eric; Nobili, Flavio

    2012-11-01

    We explored resting-state metabolic connectivity in prodromal Alzheimer's disease (pAD) patients and in healthy controls (CTR), through a voxel-wise interregional correlation analysis of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) by means of statistical parametric mapping. Baseline 18F-fluorodeoxyglucose-positron emission tomography of 36 patients with amnestic mild cognitive impairment who converted to Alzheimer's disease (AD) dementia after an average time of 2 years (pAD) and of 105 CTR were processed. The area of hypometabolism in pAD showed less metabolic connectivity in patients than in CTR (autocorrelation and correlation with large temporal and frontal areas, respectively). pAD patients showed limited correlation even in selected nonhypometabolic areas, including the hippocampi and the dorsolateral prefrontal cortex (DLFC). On the contrary, in CTR group correlation was highlighted between hippocampi and precuneus/posterior cingulate and frontal cortex, and between dorsolateral prefrontal cortex and caudate nuclei and parietal cortex. The reduced metabolic connections both in hypometabolic and nonhypometabolic areas in pAD patients suggest that metabolic disconnection (reflecting early diaschisis) may antedate remote hypometabolism (early sign of synaptic degeneration). Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Crosstalk of metabolic factors and neurogenic signaling in adult neurogenesis: Implication of metabolic regulation for mental and neurological diseases.

    Science.gov (United States)

    Gao, Chong; Wang, Qi; Chung, Sookja K; Shen, Jiangang

    2017-06-01

    Metabolic disorders like diabetes and obesity are commonly companied with neurological diseases and psychiatric disorders. Accumulating evidences indicated that cellular metabolic factors affect adult neurogenesis and have modulating effects on neurodegenerative disorders and psychiatric diseases. Adult neurogenesis contains multiple steps including proliferation of neural stem cells, lineage commitments of neural progenitor cells, maturation into functional neurons, and integration into neuronal network. Many intrinsic and extrinsic factors produced from neural stem/progenitor cells and their microenvironment or neurogenic niche take roles in modulating neurogenesis and contribute to the brain repair and functional recoveries in many neurological diseases and psychiatric disorders. In this article, we review current progress about how different growth factors, neurotrophin, neurotransmitters and transcriptional factors work on regulating neurogenic process. In particular, we emphasize the roles of the cellular metabolic factors, such as insulin/IGF signaling, incretins, and lipid metabolic signaling molecules in modulating adult neurogenesis, and discuss their impacts on neurological behaviors. We propose that the metabolic factors could be the new therapeutic targets for adult neurogenesis. Plus, the metabolism-regulating drugs have the potentials for treatment of neurodegenerative diseases and mental disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Enzymology of mammalian NAD metabolism in health and disease.

    Science.gov (United States)

    Magni, Giulio; Orsomando, Giuseppe; Raffelli, Nadia; Ruggieri, Silverio

    2008-05-01

    Mounting evidence attests to the paramount importance of the non-redox NAD functions. Indeed, NAD homeostasis is related to the free radicals-mediated production of reactive oxygen species responsible for irreversible cellular damage in infectious disease, diabetes, inflammatory syndromes, neurodegeneration and cancer. Because the cellular redox status depends on both the absolute concentration of pyridine dinucleotides and their respective ratios of oxidized and reduced forms (i.e., NAD/NADH and NADP/NADPH), it is conceivable that an altered regulation of the synthesis and degradation of NAD impairs the cell redox state and likely contributes to the mechanisms underlying the pathogenesis of the above mentioned diseases. Taking into account the recent appearance in the literature of comprehensive reviews covering different aspects of the significance of NAD metabolism, with particular attention to the enzymes involved in NAD cleavage, this monograph includes the most recent results on NAD biosynthesis in mammals and humans. Due to recent findings on nicotinamide riboside as a nutrient, its inclusion under "niacins" is proposed. Here, the enzymes involved in the de novo and reutilization pathways are overviewed.

  16. Strengthening research on relationship between metabolic syndrome and chronic liver disease

    Directory of Open Access Journals (Sweden)

    FAN Jiangao

    2013-12-01

    Full Text Available Metabolic syndrome is becoming a global epidemic disease, and it has been an important cause or risk factor for chronic liver disease in China. Recently, many studies have shown that metabolic syndrome is not only the important cause or risk factor for non-alcoholic fatty liver disease, but also closely associated with increased incidence of cirrhosis and liver cancer in patients with alcoholic liver disease, chronic hepatitis B and C, and cryptogenic liver disease. Moreover, chronic liver disease patients with metabolic syndrome have a significantly increased risk of type 2 diabetes and arteriosclerotic cardiovascular disease. These results suggest that hepatologists should pay more attention to the clinical research on the relationship between metabolic syndrome and liver disease and its management.

  17. 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.

  18. Metabolic syndrome and its components associated with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Ali Maleki

    2015-01-01

    Full Text Available Background: There is limited information on the relationship between metabolic syndrome (MetS and chronic kidney disease (CKD in the Iranian population, a group that has a high prevalence of CKD and obesity. The aim of present study was to determine the relationship between MetS and CKD in West of Iran. Materials and Methods: A total of 800 subjects aged more than 35 years admitted from 2011 to 2013 were enrolled in the study. MetS was defined based on the Adult Treatment Panel III criteria, and CKD was defined from the Kidney Disease Outcomes Quality Initiative practice guidelines. Waist circumference and body mass index were calculated, as well, blood samples were taken and lipid profile, plasma glucose levels, and serum creatinine were measured. Data were analyzed with SPSS version 17 (SPSS Inc., Chicago, IL, USA. Results: CKD was seen in 14.8% patients with MetS and 8.3% individuals without MetS. MetS was associated with an increased odds ratio (OR for a glomerular filtration rate <60 ml/min/1.73 m 2 (OR: 1.91; 95% confidence interval [CI]: 1.22-2.99; P = 0.004. Individuals with 2, 3, 4, and 5 components of the MetS had an increased OR for CKD: 2.19 (95% CI: 0.95-3.62, 2.65 (95% CI: 1.03-4.71, 2.86 (95% CI: 1.08-5.53, and 5.03 (95% CI: 1.80-8.57, respectively, compared with individuals with none of the components. Conclusion: We found a high prevalence of CKD in patients with MetS compared with the subject without MetS. Our observations raised major clinical and public health concerns in Iran, where both the MetS and kidney diseases are becoming common.

  19. 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.

  20. 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

  1. Regional cerebral glucose metabolism after pridopidine (ACR16) treatment in patients with Huntington disease.

    Science.gov (United States)

    Esmaeilzadeh, Mouna; Kullingsjö, Johan; Ullman, Henrik; Varrone, Andrea; Tedroff, Joakim

    2011-01-01

    Huntington disease is a hereditary neurodegenerative disorder resulting in loss of motor, cognitive, and behavioral functions and is characterized by a distinctive pattern of cerebral metabolic abnormalities. Pridopidine (ACR16) belongs to a novel class of central nervous system compounds in development for the treatment of Huntington disease. The objective of the study was to investigate the metabolic changes in patients with Huntington disease before and after pridopidine treatment. [(18)F]Fluorodeoxyglucose positron emission tomographic imaging was used to measure the regional cerebral metabolic rate of glucose at baseline and after 14 days of open-label pridopidine treatment in 8 patients with Huntington disease. Clinical assessments were performed using the Unified Huntington's Disease Rating Scale. Statistical parametric mapping analysis showed increased metabolic activity in several brain regions such as the precuneus and the mediodorsal thalamic nucleus after treatment. In addition, after pridopidine treatment, the correlation between the clinical status and the cerebral metabolic activity was strengthened. Our findings suggest that pridopidine induces metabolic changes in brain regions implicated as important for mediating compensatory mechanisms in Huntington disease. In addition, the finding of a strong relationship between clinical severity and metabolic activity after treatment also suggests that pridopidine treatment targets a Huntington disease-related metabolic activity pattern.

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

    Science.gov (United States)

    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.

  3. Cofactors As Metabolic Sensors Driving Cell Adaptation in Physiology and Disease

    Directory of Open Access Journals (Sweden)

    Nabil Rabhi

    2017-11-01

    Full Text Available Chromatin architectures and epigenetic fingerprint regulation are fundamental for genetically determined biological processes. Chemical modifications of the chromatin template sensitize the genome to intracellular metabolism changes to set up diverse functional adaptive states. Accumulated evidence suggests that the action of epigenetic modifiers is sensitive to changes in dietary components and cellular metabolism intermediates, linking nutrition and energy metabolism to gene expression plasticity. Histone posttranslational modifications create a code that acts as a metabolic sensor, translating changes in metabolism into stable gene expression patterns. These observations support the notion that epigenetic reprograming-linked energy input is connected to the etiology of metabolic diseases and cancer. In the present review, we introduce the role of epigenetic cofactors and their relation with nutrient intake and we question the links between epigenetic regulation and the development of metabolic diseases.

  4. Hypoglycaemia related to inherited metabolic diseases in adults

    Directory of Open Access Journals (Sweden)

    Douillard Claire

    2012-05-01

    Full Text Available Abstract In non-diabetic adult patients, hypoglycaemia may be related to drugs, critical illness, cortisol or glucagon insufficiency, non-islet cell tumour, insulinoma, or it may be surreptitious. Nevertheless, some hypoglycaemic episodes remain unexplained, and inborn errors of metabolism (IEM should be considered, particularly in cases of multisystemic involvement. In children, IEM are considered a differential diagnosis in cases of hypoglycaemia. In adulthood, IEM-related hypoglycaemia can persist in a previously diagnosed childhood disease. Hypoglycaemia may sometimes be a presenting sign of the IEM. Short stature, hepatomegaly, hypogonadism, dysmorphia or muscular symptoms are signs suggestive of IEM-related hypoglycaemia. In both adults and children, hypoglycaemia can be clinically classified according to its timing. Postprandial hypoglycaemia can be an indicator of either endogenous hyperinsulinism linked to non-insulinoma pancreatogenic hypoglycaemia syndrome (NIPHS, unknown incidence in adults or very rarely, inherited fructose intolerance. Glucokinase-activating mutations (one family are the only genetic disorder responsible for NIPH in adults that has been clearly identified so far. Exercise-induced hyperinsulinism is linked to an activating mutation of the monocarboxylate transporter 1 (one family. Fasting hypoglycaemia may be caused by IEM that were already diagnosed in childhood and persist into adulthood: glycogen storage disease (GSD type I, III, 0, VI and IX; glucose transporter 2 deficiency; fatty acid oxidation; ketogenesis disorders; and gluconeogenesis disorders. Fasting hypoglycaemia in adulthood can also be a rare presenting sign of an IEM, especially in GSD type III, fatty acid oxidation [medium-chain acyl-CoA dehydrogenase (MCAD, ketogenesis disorders (3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA lyase deficiency, and gluconeogenesis disorders (fructose-1,6-biphosphatase deficiency].

  5. Dietary fatty acids in metabolic syndrome, diabetes and cardiovascular diseases.

    Science.gov (United States)

    Cascio, Giuseppe; Schiera, Gabriella; Di Liegro, Italia

    2012-01-01

    In the last few decades, the prevalence of overweight and essential obesity has been undergoing a fast and progressive worldwide increase. Obesity has been in turn linked to type II diabetes, with the total number of diabetic patients worryingly increasing, in the last fifteen years, suggesting a pandemic phenomenon. At the same time, an increase in the prevalence of cardiovascular diseases has been also recorded. Increasing evidence suggests that the diet is involved in such escalation. In particular, the progressive globalization of food industry allowed massive supply, at a relatively low price, of a great variety of pre-packed food and bakery products, with very high energy content. Most of this food contains high amounts of saturated fatty acids (SFA) and of hydrogenated or trans fatty acids (TFA), that probably represent the prominent risk factors in the diet. Herein we will report diffusion and possible impact on health of such molecules, with reference to coronary heart disease, insulin resistance, metabolic syndrome and diabetes. We will also discuss the cellular and molecular mechanisms of action of fatty acids and fatty acid-derivatives which have been involved either in promoting or in preventing human pathologies. Free fatty acids (FFA) are not indeed only essential fuels for the organism. They also act as ligands for both membrane and nuclear receptors involved in different signaling pathways. Notably, some of these pathways can induce cell stress and apoptosis. Most important, FFA can affect glucose-induced insulin secretion and activate β-cell death. These events can be at least in part counteracted by polyunsaturated fatty acids.

  6. Influence of diseases and metabolic disorders on cow weight changes

    Directory of Open Access Journals (Sweden)

    Šárka Podlahová

    2012-10-01

    Full Text Available Requirements on increasing economic efficiency of cattle breeding force farmers to use the latest up-to-datetechnology for monitoring and management of farming quality. Regular weighing and data processing can forinstance discover mistakes that can indicate defects, e.g. nutrition deficiencies, incorrect embryonic development,health problems, demanding nursing intervention. The aim of the research was to monitor manifestations of diseasesand metabolic disorders in the course of weight curve based on data from an automated system for weighing the liveweight of dairy cows. There was used in the weighing unit for milking robots Astronaut A3 (Lely company to obtainweight data of individual cows. There were selected dairy cows with the longest period of lactation or already dryingoff, and especially dairy cows with various health problems for study. Limiting values of weight changes wereestablished after assembling a general equation of mass curve. In the sphere of the diseases there was manifestedonly ketosis in the weight curves with a loss of 10.2 kg / day (38% weight loss. The results of the study will beapplied for compiling algorithm that will be implemented in the complete management system of cattle breeding,monitoring the dairy cows every day and highlight possible deviations exceeding of physiological changes in weight.

  7. Metabolic Predictors of Incident Coronary Heart Disease in Women.

    Science.gov (United States)

    Paynter, Nina P; Balasubramanian, Raji; Giulianini, Franco; Wang, Dong D; Tinker, Lesley F; Gopal, Shuba; Deik, Amy A; Bullock, Kevin; Pierce, Kerry A; Scott, Justin; Martínez-González, Miguel A; Estruch, Ramon; Manson, JoAnn E; Cook, Nancy R; Albert, Christine M; Clish, Clary B; Rexrode, Kathryn M

    2018-02-20

    Although metabolomic profiling offers promise for the prediction of coronary heart disease (CHD), and metabolic risk factors are more strongly associated with CHD in women than men, limited data are available for women. We applied a liquid chromatography-tandem mass spectrometry metabolomics platform to measure 371 metabolites in a discovery set of postmenopausal women (472 incident CHD cases, 472 controls) with validation in an independent set of postmenopausal women (312 incident CHD cases, 315 controls). Eight metabolites, primarily oxidized lipids, were significantly dysregulated in cases after the adjustment for matching and CHD risk factors in both the discovery and validation data sets. One oxidized phospholipid, C34:2 hydroxy-phosphatidylcholine, remained associated with CHD after further adjustment for other validated metabolites. Subjects with C34:2 hydroxy-phosphatidylcholine levels in the highest quartile had a 4.7-fold increase in CHD odds in comparison with the lowest quartile; C34:2 hydroxy-phosphatidylcholine also significantly improved the area under the curve ( P <0.01) for CHD. The C34:2 hydroxy-phosphatidylcholine findings were replicated in a third replication data set of 980 men and women (230 cardiovascular events) with a stronger association observed in women. These data replicate known metabolite predictors, identify novel markers, and support the relationship between lipid oxidation and subsequent CHD. © 2018 American Heart Association, Inc.

  8. Meal frequency and timing: impact on metabolic disease risk.

    Science.gov (United States)

    Varady, Krista A

    2016-10-01

    The purpose of this article is to provide an overview of the most recent human intervention trials that have examined the impact of meal frequency or meal timing on metabolic disease risk factors. Findings from intervention studies published over the past 12 months indicate that weight loss may be more pronounced with decreased meal frequency (two meals per day) versus increased meal frequency (six meals per day) under hypocaloric conditions. However, under isocaloric conditions, no effect on body weight was noted. Plasma lipid concentrations and glucoregulatory factors (fasting glucose, insulin, and insulin sensitivity) were not affected by alterations in meal frequency. As for meal timing, delaying the lunchtime meal by 3.5 h (from 1.30 p.m. to 4.30 p.m.) has no impact on body weight, but may impair glucose tolerance in young healthy adults. In sum, altering meal frequency has little impact on body weight, plasma lipids, or glucoregulatory factors, whereas eating the majority of calories later in the day may be detrimental for glycemic control. These preliminary findings, however, still require confirmation by longer term, larger scale controlled trials.

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

    DEFF Research Database (Denmark)

    Lundgren, J D; Battegay, M; Behrens, G

    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...... interactions and compromised adherence. Specialists in HIV and specialists in metabolic diseases should consult each other, in particular in difficult-to-treat cases. CONCLUSION: Multiple and relatively simple approaches exist to prevent metabolic diseases in HIV-infected persons; priority should be given...

  10. Bile Acid Signaling in Liver Metabolism and Diseases

    Directory of Open Access Journals (Sweden)

    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.

  11. Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease.

    Science.gov (United States)

    Harambat, Jérôme; Kunzmann, Kevin; Azukaitis, Karolis; Bayazit, Aysun K; Canpolat, Nur; Doyon, Anke; Duzova, Ali; Niemirska, Anna; Sözeri, Betul; Thurn-Valsassina, Daniela; Anarat, Ali; Bessenay, Lucie; Candan, Cengiz; Peco-Antic, Amira; Yilmaz, Alev; Tschumi, Sibylle; Testa, Sara; Jankauskiene, Augustina; Erdogan, Hakan; Rosales, Alejandra; Alpay, Harika; Lugani, Francesca; Arbeiter, Klaus; Mencarelli, Francesca; Kiyak, Aysel; Dönmez, Osman; Drozdz, Dorota; Melk, Anette; Querfeld, Uwe; Schaefer, Franz

    2017-12-01

    Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m 2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  12. Dysregulation of Iron Metabolism in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Satoru Oshiro

    2011-01-01

    Full Text Available Dysregulation of iron metabolism has been observed in patients with neurodegenerative diseases (NDs. Utilization of several importers and exporters for iron transport in brain cells helps maintain iron homeostasis. Dysregulation of iron homeostasis leads to the production of neurotoxic substances and reactive oxygen species, resulting in iron-induced oxidative stress. In Alzheimer's disease (AD and Parkinson's disease (PD, circumstantial evidence has shown that dysregulation of brain iron homeostasis leads to abnormal iron accumulation. Several genetic studies have revealed mutations in genes associated with increased iron uptake, increased oxidative stress, and an altered inflammatory response in amyotrophic lateral sclerosis (ALS. Here, we review the recent findings on brain iron metabolism in common NDs, such as AD, PD, and ALS. We also summarize the conventional and novel types of iron chelators, which can successfully decrease excess iron accumulation in brain lesions. For example, iron-chelating drugs have neuroprotective effects, preventing neural apoptosis, and activate cellular protective pathways against oxidative stress. Glial cells also protect neurons by secreting antioxidants and antiapoptotic substances. These new findings of experimental and clinical studies may provide a scientific foundation for advances in drug development for NDs.

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

    Science.gov (United States)

    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.

  14. Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network.

    Science.gov (United States)

    Galhardo, Mafalda; Sinkkonen, Lasse; Berninger, Philipp; Lin, Jake; Sauter, Thomas; Heinäniemi, Merja

    2014-02-01

    Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types impact tissue homeostasis. Here, the link between the metabolic and gene regulatory networks was studied through experimental and computational analysis. Integrating gene regulation data with a human metabolic network prompted the establishment of an open-sourced web portal, IDARE (Integrated Data Nodes of Regulation), for visualizing various gene-related data in context of metabolic pathways. Motivated by increasing availability of deep sequencing studies, we obtained ChIP-seq data from widely studied human umbilical vein endothelial cells. Interestingly, we found that association of metabolic genes with multiple transcription factors (TFs) enriched disease-associated genes. To demonstrate further extensions enabled by examining these networks together, constraint-based modeling was applied to data from human preadipocyte differentiation. In parallel, data on gene expression, genome-wide ChIP-seq profiles for peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (CEBP) α, liver X receptor (LXR) and H3K4me3 and microRNA target identification for miR-27a, miR-29a and miR-222 were collected. Disease-relevant key nodes, including mitochondrial glycerol-3-phosphate acyltransferase (GPAM), were exposed from metabolic pathways predicted to change activity by focusing on association with multiple regulators. In both cell types, our analysis reveals the convergence of microRNAs and TFs within the branched chain amino acid (BCAA) metabolic pathway, possibly providing an explanation for its downregulation in obese and diabetic conditions.

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

    Science.gov (United States)

    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.

  16. Redox metabolism abnormalities in autistic children associated with mitochondrial disease.

    Science.gov (United States)

    Frye, R E; Delatorre, R; Taylor, H; Slattery, J; Melnyk, S; Chowdhury, N; James, S J

    2013-06-18

    Research studies have uncovered several metabolic abnormalities associated with autism spectrum disorder (ASD), including mitochondrial disease (MD) and abnormal redox metabolism. Despite the close connection between mitochondrial dysfunction and oxidative stress, the relation between MD and oxidative stress in children with ASD has not been studied. Plasma markers of oxidative stress and measures of cognitive and language development and ASD behavior were obtained from 18 children diagnosed with ASD who met criteria for probable or definite MD per the Morava et al. criteria (ASD/MD) and 18 age and gender-matched ASD children without any biological markers or symptoms of MD (ASD/NoMD). Plasma measures of redox metabolism included reduced free glutathione (fGSH), oxidized glutathione (GSSG), the fGSH/GSSG ratio and 3-nitrotyrosine (3NT). In addition, a plasma measure of chronic immune activation, 3-chlorotyrosine (3CT), was also measured. Language was measured using the preschool language scale or the expressive one-word vocabulary test (depending on the age), adaptive behaviour was measured using the Vineland Adaptive Behavior Scale (VABS) and core autism symptoms were measured using the Autism Symptoms Questionnaire and the Social Responsiveness Scale. Children with ASD/MD were found to have lower scores on the communication and daily living skill subscales of the VABS despite having similar language and ASD symptoms. Children with ASD/MD demonstrated significantly higher levels of fGSH/GSSG and lower levels of GSSG as compared with children with ASD/NoMD, suggesting an overall more favourable glutathione redox status in the ASD/MD group. However, compare with controls, both ASD groups demonstrated lower fGSH and fGSH/GSSG, demonstrating that both groups suffer from redox abnormalities. Younger ASD/MD children had higher levels of 3CT than younger ASD/NoMD children because of an age-related effect in the ASD/MD group. Both ASD groups demonstrated significantly

  17. Marking of metabolites in the diagnostics of metabolic diseases and in the investigation of xenobiotics metabolism using NMR spectroscopy.

    Science.gov (United States)

    Krawczyk, Hanna

    2016-10-25

    There are currently no sound estimates of the number of children born with a serious congenital disorder attributable to genetic or environmental causes (World Health Organization) but there is a supposed number of babies born with birth defects per year: in the world approximately 7.9 million children (6% of births). There is conducted population-based screening by the individual countries. The specialised methods are used when it is not possible to diagnose disease in screening. In recent years in the diagnostics of these disorders the methods of Magnetic Resonance Spectroscopy of the brain (in vivo 1 H-MRS) and high resolution NMR spectroscopy gain in importance. The manuscript focused on developing the method of marking the metabolic diseases markers of various origins using NMR spectroscopy (including synthesis of markers). Considering the disorders occurring among children, according to Hoffman, Zschocke, Nyhan, there are three following groups of inherited metabolic diseases: disorders of intermediary metabolism, disorders of the biosynthesis and breakdown of complex molecules and neurotransmitter defects and related disorders. The presented investigation is focused on: a study of selected compounds that cause disorders of intermediary metabolism, a study of compounds that cause disorders of the biosynthesis and breakdown of complex molecules and a study of compounds that cause neurotransmitter defects and related disorders. In the subsequent chapter of manuscript there are presented the results of investigation concerning the metabolism of xenobiotics that could potentially be used in therapy of inherited metabolic diseases, basing on stilbene derivatives. In the last chapter there are presented the results of experiments with creatinine- the metabolite produced in muscles. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Effects of Soy on Metabolic Biomarkers of Cardiovascular Disease in Elderly Women with the Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Afsaneh Bakhtiary

    2010-09-01

    Full Text Available Objective: To ascertain the effects of soy [in the forms of Textured Soy Protein (TSP and soy-nut] onlipid profiles, apolipoproteins, inflammatory and prothrombotic markers and blood pressure in elderlywomen with the metabolic syndrome.Materials and methods: The study is a 12-week parallel randomized controlled trial that was conductedin rural health centres of Babol, Iran. The participants were 75 women 60-70 years old with the metabolicsyndrome who were randomized to one of the three groups of soy-nut (35g/d, TSP (35g/d and control.Blood pressure and blood biochemical markers were measured at baseline and at the end of the studyincluding, triglyceride, cholesterol, HDL-C, LDL-C, VLDL-C, ApoB100, ApoAI, CRP and fibrinogen.Results: The soy-nut improved significantly LDL-C, VLDL-C and Apo B100 (P<0.05 while fewer improvementsbut significant were observed in these variables in the TSP group only when compared with themean changes from the baseline (P<0.001. Similar result was found for Apo AI in the treatment groups(P<0.01. Serum total cholesterol decreased significantly in the treatment groups compared with controlgroup (P<0.005. The differences from control for triglyceride, HDL-C, fibrinogen, CRP and bloodpressure were not significant.Conclusion: Both forms of soy while improved lipids profiles the soy-nut contribution was more to thisimprovement than the TSP. Therefore, moderate daily intake of soy may be a safe, cheap and practicalmethod to improve cardiovascular disease risk and also reduce the need for medical treatment.

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

    Science.gov (United States)

    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. PMID:21318173

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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...... first as the metabolic syndrome (metabolically unhealthy: ≥3 metabolic abnormalities) and second as the number of metabolic abnormalities. We used Cox proportional hazards regression to assess associations between baseline characteristics and cardiovascular risk. Over 13 years of follow-up, 1101 women...

  2. [Clinical analysis of metabolic syndrome in vertiginous diseases].

    Science.gov (United States)

    Yamanaka, Toshiaki; Fukuda, Takehiko; Sawai, Yachiyo; Shirota, Shiho; Shimizu, Naoki; Murai, Takayuki; Okamoto, Hideyuki; Fujita, Nobuya; Hosoi, Hiroshi

    2011-01-01

    To explore the relationship between metabolic syndrome and vertigo, we measured waist circumference, plasma glucose, triglycerides and blood pressure in 333 subjects aged 20-79 years with vertigo. We found overall metabolic syndrome prevalence defined by Japanese diagnostic criteria to be 13.2%, similar to that in other national surveys by the Japanese Ministry of Health, Labour and Welfare. The 6-fold higher prevalence in men over women exceeded that of other reports, however. The highest frequency was in vertebrobasilar insufficiency (VBI) disorders, suggesting that conditions such as VBI in men with vertigo could involve metabolic syndrome as a risk factor for vertigo incidence.

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

    OpenAIRE

    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 stud...

  4. 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...

  5. 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...

  6. Molecular Connections Between Arousal and Metabolic Disease: Orexin and Modafinil

    National Research Council Canada - National Science Library

    Benoit, Stephen C

    2007-01-01

    .... Further, some anti-fatigue pharmacologies (e.g. modafinil) are already used in military settings, though their long-term effects on metabolism or central nervous system function are not well-understood...

  7. Molecular Connections between Arousal and Metabolic Disease: Orexin and Modafinil

    National Research Council Canada - National Science Library

    Benoit, Stephen C

    2008-01-01

    .... Further some anti-fatigue pharmacologies (e.g. modafinil) are already used in military settings though their long-term effects on metabolism or central nervous system function are not well-understood...

  8. The interaction of hepatic lipid and glucose metabolism in liver diseases

    NARCIS (Netherlands)

    Bechmann, Lars P.; Hannivoort, Rebekka A.; Gerken, Guido; Hotamisligil, Goekhan S.; Trauner, Michael; Canbay, Ali

    It is widely known that the liver is a central organ in lipogenesis, gluconeogenesis and cholesterol metabolism. However, over the last decades, a variety of pathological conditions highlighted the importance of metabolic functions within the diseased liver. As observed in Western societies, an

  9. Metabolic syndrome: is equine disease comparable to what we know in humans?

    Science.gov (United States)

    Ertelt, Antonia; Barton, Ann-Kristin; Schmitz, Robert R; Gehlen, Heidrun

    2014-01-01

    This review summarizes similarities and differences between the metabolic syndromes in humans and equines, concerning the anatomy, symptoms, and pathophysiological mechanisms. In particular, it discusses the structure and distribution of adipose tissue and its specific metabolic pathways. Furthermore, this article provides insights and focuses on issues concerning laminitis in horses and cardiovascular diseases in humans, as well as their overlap. PMID:24894908

  10. 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

  11. Hepcidin: an important iron metabolism regulator in chronic kidney disease.

    Science.gov (United States)

    Antunes, Sandra Azevedo; Canziani, Maria Eugênia Fernandes

    2016-01-01

    Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD) is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production. The elevation of hepcidin has been associated with infection, inflammation, atherosclerosis, insulin resistance and oxidative stress. Some strategies were tested to reduce the effects of hepcidin in patients with CKD, however more studies are necessary to assess the impact of its modulation in the management of anemia in this population. Resumo Anemia é uma complicação frequente e seu impacto na morbimortalidade é bem conhecido em pacientes com doença renal crônica (DRC). A descoberta da hepcidina e de suas funções contribuíram para melhor compreensão dos distúrbios do metabolismo de ferro na anemia da DRC. Hepcidina é um peptídeo produzido principalmente pelos hepatócitos, e através de sua ligação com a ferroportina, regula a absorção de ferro no duodeno e sua liberação das células de estoque. Altas concentrações de hepcidina descritas em pacientes com DRC, principalmente em estádios mais avançados, são atribuídas à diminuição da excreção renal e ao aumento de sua produção. Elevação de hepcidina tem sido associada à ocorrência de infecção, inflamação, aterosclerose, resistência à insulina e estresse oxidativo. Algumas estratégias foram testadas para diminuir os efeitos da hepcidina em pacientes com DRC, entretanto, serão necessários mais estudos para avaliar o impacto de sua modulação no manejo da anemia nessa população.

  12. Can we prevent obesity-related metabolic diseases by dietary modulation of the gut microbiota?

    DEFF Research Database (Denmark)

    Brahe, Lena Kirchner; Astrup, Arne; Larsen, Lesli Hingstrup

    2016-01-01

    Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut...... microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic...... diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity...

  13. 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

  14. 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.

  15. 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

    of atherothrombotic disease and metabolic syndrome, and to assess the importance of the kind of treatment received and of membership of a patients' association. METHODS: In total, 218 patients with psoriasis (mean age 45.5 years, range 18-83), who were being treated with methotrexate or biological drugs responded...... 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...

  16. 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

  17. Can We Prevent Obesity-Related Metabolic Diseases by Dietary Modulation of the Gut Microbiota?

    Science.gov (United States)

    Brahe, Lena K; Astrup, Arne; Larsen, Lesli H

    2016-01-01

    Obesity increases the risk of type 2 diabetes, cardiovascular diseases, and certain cancers, which are among the leading causes of death worldwide. Obesity and obesity-related metabolic diseases are characterized by specific alterations in the human gut microbiota. Experimental studies with gut microbiota transplantations in mice and in humans indicate that a specific gut microbiota composition can be the cause and not just the consequence of the obese state and metabolic disease, which suggests a potential for gut microbiota modulation in prevention and treatment of obesity-related metabolic diseases. In addition, dietary intervention studies have suggested that modulation of the gut microbiota can improve metabolic risk markers in humans, but a causal role of the gut microbiota in such studies has not yet been established. Here, we review and discuss the role of the gut microbiota in obesity-related metabolic diseases and the potential of dietary modulation of the gut microbiota in metabolic disease prevention and treatment. © 2016 American Society for Nutrition.

  18. Metabolic reprogramming in the pathogenesis of chronic lung diseases including BPD, COPD, and pulmonary fibrosis.

    Science.gov (United States)

    Zhao, Haifeng; Dennery, Phyllis A; Yao, Hongwei

    2018-01-04

    The metabolism of nutrient substrates including glucose, glutamine and fatty acids provides acetyl-CoA for the tricarboxylic acid cycle to generate energy, and metabolites for the biosynthesis of biomolecules including nucleotides, proteins, and lipids. It has been shown that metabolism of glucose, fatty acid, and glutamine plays important roles in modulating cellular proliferation, differentiation, apoptosis, autophagy, senescence, and inflammatory responses. All these cellular processes contribute to the pathogenesis of chronic lung diseases, including bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis. Recent studies demonstrate that metabolic reprogramming occurs in patients with and animal models of chronic lung diseases, suggesting that metabolic dysregulation may participate in the pathogenesis and progression of these diseases. In this review, we briefly discuss the catabolic pathways for glucose, glutamine and fatty acids, and focus on how metabolic reprogramming of these pathways impacts cellular functions and leads to the development of these chronic lung diseases. We also highlight how targeting metabolic pathways can be utilized in the prevention and treatment of these diseases.

  19. One-Carbon Metabolism in Health and Disease.

    Science.gov (United States)

    Ducker, Gregory S; Rabinowitz, Joshua D

    2017-01-10

    One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing. An emerging theme is the biological importance of mitochondrial 1C reactions, both for producing 1C units that are exported to the cytosol and for making additional products, including glycine and NADPH. Increased clarity regarding differential folate pathway usage in cancer, stem cells, development, and adult physiology is reviewed and highlights new opportunities for selective therapeutic intervention. Copyright © 2017. Published by Elsevier Inc.

  20. Metabolic control of von Gierke disease (glycogen storage disease type Ia) in pregnancy: maintenance of euglycemia with cornstarch.

    Science.gov (United States)

    Johnson, M P; Compton, A; Drugan, A; Evans, M I

    1990-03-01

    In patients with glycogen storage disease type Ia, glucose-6-phosphatase deficiency reduces the liver's ability to generate free glucose from glycogen. Without a continuous, exogenous source of glucose, severe hypoglycemia and subsequent metabolic perturbations occur. Our observations of a patient with glycogen storage disease type Ia, who also had a clomiphene-induced triplet gestation, suggest that cornstarch, which can be catabolized by debranching enzymes, may be used to maintain a constant state of maternal and fetal euglycemia and correct many metabolic abnormalities. Our data suggest that patients with glycogen storage disease type Ia can be safely managed in pregnancy under a tightly monitored and regulated protocol of raw cornstarch feedings.

  1. 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.

  2. Metabolic Engineering of Chemical Defence Pathways in Plant Disease Control

    DEFF Research Database (Denmark)

    Rook, Frederik

    2016-01-01

    with antimicrobial properties for use in crop protection. It presents an overview of the metabolic engineering efforts made in the area of plant chemical defence. For in-depth information on the characteristics of a specific class of chemical defence compounds, the reader is referred to the specialized reviews......Plants produce a wide variety of specialized (or secondary) metabolites that function as chemical defence compounds and provide protection against microbial pathogens or herbivores. This chapter focuses on the metabolic engineering of biosynthetic pathways for plant chemical defence compounds...

  3. Fat metabolism during exercise in patients with mitochondrial disease

    DEFF Research Database (Denmark)

    Jeppesen, Tina Dysgaard; Orngreen, Mette Cathrine; Van Hall, Gerrit

    2009-01-01

    of palmitate and total free fatty acids, glucose mobilization, and total carbohydrate oxidation. RESULTS: Fat turnover and plasma concentrations of palmitate and total free fatty acids were similar in patients and healthy subjects at rest and during exercise. In line with the higher relative workload......OBJECTIVE: To determine whether patients with defects of the respiratory chain have metabolic adaptations that promote a preferential use of fats or carbohydrates, similar to what is observed in metabolic myopathies affecting glycolysis or fat oxidation. DESIGN: Causation and case-control study...

  4. Gut Microbiota Dysbiosis Drives and Implies Novel Therapeutic Strategies for Diabetes Mellitus and Related Metabolic Diseases

    Directory of Open Access Journals (Sweden)

    Xuan Li

    2017-12-01

    Full Text Available Accumulating evidence over the past decade has linked the development of metabolic syndrome related to diabetes to variations in gut microbiota, an emerging, critical homeostatic regulator of host energy metabolism and immune responses. Mechanistic studies in rodent models have revealed an ever-increasing multitude of molecular mechanisms whereby the gut microbiota interacts with various host sensing and signaling pathways, leading to modulation of endocrine system, immune responses, nervous system activity, and hence, the predisposition to metabolic diseases. Remarkably, the microbiota-driven immune responses in metabolic tissues and the host nutrient-sensing mechanisms of gut microbial metabolites, in particular short-chain fatty acids, have been significantly associated with the proneness to diabetes and related disorders. This review will synthesize the recent efforts on unraveling the mediating role of gut microbiota in the pathogenesis of metabolic diseases, aiming to reveal new therapeutic opportunities.

  5. Generalized metabolic bone disease in Neurofibromatosis type I

    Science.gov (United States)

    Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1), but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical, and pathological level the bone involvement ...

  6. Under- and overnutrition and evidence of metabolic disease risk in ...

    African Journals Online (AJOL)

    Conclusion: Stunting levels were higher in the boys than in the girls in mid to late childhood in a rural setting in South Africa, while the girls had a higher prevalence of overweight and obesity than the boys. Pre-hypertension prevalence in the boys and girls was high. Other metabolic risk factors, i.e. impaired FG and lipids, ...

  7. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

    NARCIS (Netherlands)

    van Dijk, Gertjan; van Heijningen, Steffen; Reijne, Aaffien C.; Nyakas, Csaba; van der Zee, Eddy A.; Eisel, Ulrich L. M.

    2015-01-01

    Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Muscle glucose metabolism in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Sancho-Muñoz, Antonio; Trampal, Carlos; Pascual, Sergi; Martínez-Llorens, Juana; Chalela, Roberto; Gea, Joaquim; Orozco-Levi, Mauricio

    2014-06-01

    Muscle dysfunction is one of the most extensively studied manifestations of COPD. Metabolic changes in muscle are difficult to study in vivo, due to the lack of non-invasive techniques. Our aim was to evaluate metabolic activity simultaneously in various muscle groups in COPD patients. Thirty-nine COPD patients and 21 controls with normal lung function, due to undergo computed axial and positron emission tomography for staging of localized lung lesions were included. After administration of 18-fluordeoxyglucose, images of 2 respiratory muscles (costal and crural diaphragm, and rectus abdominus) and 2 peripheral muscles (brachial biceps and quadriceps) were obtained, using the standard uptake value as the glucose metabolism index. Standard uptake value was higher in both portions of the diaphragm than in the other muscles of all subjects. Moreover, the crural diaphragm and rectus abdominus showed greater activity in COPD patients than in the controls (1.8±0.7 vs 1.4±0.8; and 0.78±0.2 vs 0.58±0.1; respectively, P<.05). A similar trend was observed with the quadriceps. In COPD patients, uptake in the two respiratory muscles and the quadriceps correlated directly with air trapping (r=0.388, 0.427 and 0.361, respectively, P<.05). There is greater glucose uptake and metabolism in the human diaphragm compared to other muscles when the subject is at rest. Increased glucose metabolism in the respiratory muscles (with a similar trend in their quadriceps) of COPD patients is confirmed quantitatively, and is directly related to the mechanical loads confronted. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  11. The metabolic syndrome in thyroid disease: A report from Nigeria

    Directory of Open Access Journals (Sweden)

    Anthonia O Ogbera

    2012-01-01

    Full Text Available Background: The objective of this study was to determine the prevalence of the metabolic syndrome and its components in people with thyroid disorders. Materials and Methods: 112 subjects with a history of thyroid disorders were consecutively enrolled for the study. Clinical data were obtained by interviewing the patients and referring to their case folders and prescriptions. The subjects were categorized into three: thyrotoxic, those with hypothyroidism and those with nontoxic goiters, based on clinical parameters and or thyroid function tests. The study subjects were weighed and their anthropometric indices were documented. The laboratory parameters that were analyzed included total cholesterol, high-density and low-density cholesterol and triglyceride. Statistical analysis was performed using Student′s t test, one-way analysis of variance (ANOVA test and chi-square test. Results: The study subjects were aged between 14 and 76 years, with a mean age of 44.5 years, and the female:male ratio was 97:15. The mean age and anthropometric indices were comparable in subjects with thyrotoxicosis, hypothyroidism and euthyroidism. The overall prevalence of the metabolic syndrome was 28% and the frequency of occurrence of the metabolic syndrome in subjects with thyrotoxicosis, hypothyroidism and nontoxic goiter was 24%, 40% and 42%, respectively. The commonest occurring metabolic syndrome defining criterion was dysglycemia, while hypertension and elevated triglyceride were the least documented of the criteria. Conclusion: Metabolic syndrome occurs in 1 in every 4 persons with thyroid disorders, and as such, routine screening for this cardiovascular risk factor may be of benefit in this group of people, especially in those with hypothyroidism.

  12. Metabolic disorders and chronic viral disease: the case of HIV and HCV.

    Science.gov (United States)

    Slama, L; Le Camus, C; Serfaty, L; Pialoux, G; Capeau, J; Gharakhanian, S

    2009-02-01

    The importance of metabolic disorders in the pathophysiology of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections is becoming increasingly apparent. Metabolic anomalies, with their potential for multiple-organ involvement, are to be expected, given the chronic nature of these diseases, and the intracellular dysregulation associated with them. Not only have the endocrine and cytokine metabolic anomalies seen in HIV and HCV infections been linked with the metabolic syndrome, but they also appear to have some pathways in common. Studying the differences and similarities between these metabolic anomalies may add to our understanding of HIV and HCV infection, and provide guidance on how to treat these chronic diseases. This review highlights the principal underlying factors for metabolic disorders in these chronic viral diseases-namely insulin resistance and liver damage. Both the chronic viral state itself and the host immune response give rise to glucose and lipid metabolic disorders that, in turn, are risk factors for hepatic damage. The various interactions between HIV and/or HCV with insulin resistance, type 2 diabetes, steatosis and fibrogenesis should be considered when determining the treatment and long-term follow-up of patients. Recent data indicate that HCV clearance improves insulin resistance and hepatic function in HCV-infected patients treated with interferon with or without ribavirin.

  13. Relevance of the Human Genome Project to inherited metabolic disease.

    Science.gov (United States)

    Burn, J

    1994-01-01

    The Human Genome Project is an international effort to identify the complete structure of the human genome. HUGO, the Human Genome Organization, facilitates international cooperation and exchange of information while the Genome Data Base will act as the on-line information retrieval and storage system for the huge amount of information being accumulated. The clinical register MIM (Mendelian Inheritance in Man) established by Victor McKusick is now an on-line resource that will allow biochemists working with inborn errors of metabolism to access the rapidly expanding body of knowledge. Biochemical and molecular genetics are complementary and should draw together to find solutions to the academic and clinical problems posed by inborn errors of metabolism.

  14. [Association of metabolic syndrome and oxidative stress with ischemic heart disease in middle-aged persons].

    Science.gov (United States)

    Cerniauskiene, Liucija Rita; Luksiene, Dalia Ieva; Tamosiūnas, Abdonas; Reklaitiene, Regina; Margeviciene, Lilija

    2008-01-01

    The aim of this study was to evaluate the association of metabolic syndrome and oxidative stress with ischemic heart disease in middle-aged persons (men and women aged 45-64 years). In this study, we have used data of 533 persons (247 men and 286 women) aged 45-64 years from Kaunas population cohort investigated according to WHO MONICA study protocol during 2001-2002 in whom concentrations of malondialdehyde, a marker of lipid peroxidation, and antioxidant vitamin E in blood serum were determined. Metabolic syndrome was defined by the criteria of Adult Treatment Panel III. Oxidative stress was determined in the presence of increased level of malondialdehyde (> or =5 micromol/L) and decreased level of lipid-standardized vitamin E (Ischemic heart disease was diagnosed in 19.8% of men and 21.3% of women. The frequency of ischemic heart disease among persons (men and women) with metabolic syndrome was significantly higher than among persons without metabolic syndrome (27.4% vs. 17.8%, respectively; odds ratio, 1.63; P=0.032). The frequency of ischemic heart disease among persons with oxidative stress was significantly higher than among persons without oxidative stress (29.1% vs. 17.6%, respectively; odds ratio, 1.88; P=0.029). The highest prevalence of ischemic heart disease (30.0%) was among persons with metabolic syndrome and oxidative stress, and the lowest prevalence of this disease (13.8%) was among persons without metabolic syndrome and without oxidative stress (odds ratio, 2.54; P=0.017). These data were adjusted by sex and age. Metabolic syndrome and oxidative stress are significantly associated with ischemic heart disease among 45-64-year-old persons.

  15. 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)

  16. 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

  17. 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.

  18. 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.

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

    Science.gov (United States)

    Haregu, Tilahun Nigatu; Oti, Samuel; Ngomi, Nicholas; Khayeka-Wandabwa, Christopher; Egondi, Thaddaeus; Kyobutungi, Catherine

    2016-01-01

    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. The goal of the study was to describe the interlinkage among common cardio-metabolic disease markers in an African setting. 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. 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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Relationship between the oral cavity and cardiovascular diseases and metabolic syndrome.

    Science.gov (United States)

    Carramolino-Cuéllar, Esther; Tomás, Inmaculada; Jiménez-Soriano, Yolanda

    2014-05-01

    The components of the human body are closely interdependent; as a result, disease conditions in some organs or components can influence the development of disease in other body locations. The effect of oral health upon health in general has been investigated for decades by many epidemiological studies. In this context, there appears to be a clear relationship between deficient oral hygiene and different systemic disorders such as cardiovascular disease and metabolic syndrome. The precise relationship between them is the subject of ongoing research, and a variety of theories have been proposed, though most of them postulate the mediation of an inflammatory response. This association between the oral cavity and disease in general requires further study, and health professionals should be made aware of the importance of adopting measures destined to promote correct oral health. The present study conducts a Medline search with the purpose of offering an update on the relationship between oral diseases and cardiovascular diseases, together with an evaluation of the bidirectional relationship between metabolic syndrome and periodontal disease. Most authors effectively describe a moderate association between the oral cavity and cardiovascular diseases, though they also report a lack of scientific evidence that oral alterations constitute an independent cause of cardiovascular diseases, or that their adequate treatment can contribute to prevent such diseases. In the case of metabolic syndrome, obesity and particularly diabetes mellitus may be associated to an increased susceptibility to periodontitis. However, it is not clear whether periodontal treatment is able to improve the systemic conditions of these patients.

  2. 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...

  3. Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model.

    Science.gov (United States)

    Fong, Sheng; Teo, Emelyne; Ng, Li Fang; Chen, Ce-Belle; Lakshmanan, Lakshmi Narayanan; Tsoi, Sau Yee; Moore, Philip Keith; Inoue, Takao; Halliwell, Barry; Gruber, Jan

    2016-09-22

    Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ 1-42 form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ 1-42 expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease, and also confirm that Aβ-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism

    NARCIS (Netherlands)

    Peters, Heidi; Buck, Nicole; Wanders, Ronald; Ruiter, Jos; Waterham, Hans; Koster, Janet; Yaplito-Lee, Joy; Ferdinandusse, Sacha; Pitt, James

    2014-01-01

    Two siblings with fatal Leigh disease had increased excretion of S-(2-carboxypropyl)cysteine and several other metabolites that are features of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, a rare defect in the valine catabolic pathway associated with Leigh-like disease. However, this

  6. Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity.

    Science.gov (United States)

    McAlindon, T E; Gulin, J; Chen, T; Klug, T; Lahita, R; Nuite, M

    2001-01-01

    Estrogen metabolism in women with SLE is weighted towards 16alpha-hydroxyestrone, an estrogenic compound that might fuel disease activity. Indole-3-carbinol (I3C) is a nutritional compound that can shift estrogen metabolism towards less estrogenic metabolites. However, the effects of I3C in women with SLE have not been studied. Open-label 1-week metabolic study of 375 mg/day I3C was carried out in women with SLE, followed by a 3-month observational period for disease activity. The primary outcome measure was the change in ratio of urinary 2:16alpha hydroxyestrone levels. Secondary measures included the SLE Disease Activity Index. Seventeen clinically premenopausal women fulfilling ACR criteria for probable/definite SLE (mean age 37.9 y, range 20-49 y, mean disease duration 4.3 y, range 0.5-15) completed the 1-week metabolic study; 12 took I3C for 3 months. The mean 2:16alpha hydroxyestrone ratio increased by 1.84 to 3.15 (P = 0.0001). Mean SLEDAI scores were 10.0 (baseline); 6.25 (3 months); and 8.8 (3 months after withdrawal; P = NS). Women with SLE can manifest a metabolic response to I3C and might benefit from its antiestrogenic effects. We did not observe any striking effects on SLE disease activity during the 3-month observational period.

  7. CEREBROVASCULAR DISEASES: THE POSSIBILITIES AND EFFICIENCY OF METABOLIC THERAPY

    Directory of Open Access Journals (Sweden)

    Kh. Ya. Umarova

    2014-07-01

    Full Text Available Acute and chronic brain ischemia is accompanied by complex metabolic rearrangements in the neurons. The ability of the cells to survive is largely determined by the presence of energy substrates and oxygen, the synthesis of neurotransmitters, and some other factors. The increasedpersistence of nerve tissue in ischemia and chances of recovering the impaired function can be achieved by the use of neuroprotective and neurotrophic agents. The efficiency of neurometabolic therapy is considered using Ceraxon and Actovegin as an example. It is emphasized that theefficiency of their administration can be achieved by the mandatory concurrent use of a wide range of nondrug treatments.

  8. CEREBROVASCULAR DISEASES: THE POSSIBILITIES AND EFFICIENCY OF METABOLIC THERAPY

    Directory of Open Access Journals (Sweden)

    Kh. Ya. Umarova

    2013-01-01

    Full Text Available Acute and chronic brain ischemia is accompanied by complex metabolic rearrangements in the neurons. The ability of the cells to survive is largely determined by the presence of energy substrates and oxygen, the synthesis of neurotransmitters, and some other factors. The increasedpersistence of nerve tissue in ischemia and chances of recovering the impaired function can be achieved by the use of neuroprotective and neurotrophic agents. The efficiency of neurometabolic therapy is considered using Ceraxon and Actovegin as an example. It is emphasized that theefficiency of their administration can be achieved by the mandatory concurrent use of a wide range of nondrug treatments.

  9. 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 ...

  10. Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic.

    Science.gov (United States)

    Mendrick, Donna L; Diehl, Anna Mae; Topor, Lisa S; Dietert, Rodney R; Will, Yvonne; La Merrill, Michele A; Bouret, Sebastien; Varma, Vijayalaskshmi; Hastings, Kenneth L; Schug, Thaddeus T; Emeigh Hart, Susan G; Burleson, Florence G

    2017-11-02

    Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic, a Society of Toxicology Contemporary Concepts in Toxicology (CCT) workshop was held on March 11, 2017. The meeting was convened to raise awareness of metabolic syndrome and its associated diseases and serve as a melting pot with scientists of multiple disciplines (e.g., toxicologists, clinicians, regulators) so as to spur research and understanding of this condition. The criteria for metabolic syndrome include obesity, dyslipidemia (low HDL and/or elevated triglycerides), elevated blood pressure, and alterations in glucose metabolism. It can lead to a greater potential of type 2 diabetes, lipid disorders, cardiovascular disease, hepatic steatosis and other circulatory disorders. While there are no approved drugs specifically for this syndrome, many drugs target diseases associated with this syndrome thus potentially increasing the likelihood of drug-drug interactions. There is currently significant research focusing on understanding the key pathways that control metabolism, which would be likely targets of risk factors (e.g., exposure to xenobiotics, genetics) and lifestyle factors (e.g., microbiome, nutrition, and exercise) that contribute to metabolic syndrome. Understanding these pathways could also lead to the development of pharmaceutical interventions. As individuals with metabolic syndrome have signs similar to that of toxic responses (e.g., oxidative stress and inflammation) and organ dysfunction, these alterations should be taken into account in drug development. With the increasing frequency of metabolic syndrome in the general population, the idea of a "normal" individual may need to be redefined. This paper reports on the substance and outcomes of this workshop. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the public domain in the US.

  11. A key problem and challenge for hepatology: Obesity-related metabolic liver diseases.

    Science.gov (United States)

    Balaban, Yasemin Hatice

    2011-06-27

    With the arrival of the new millennium, gastroenterologists have been faced with the problem of metabolic liver diseases associated with obesity. The active role of the liver in metabolism and inflammation make it a key organ in the war against the rapidly-spreading world-wide epidemic of obesity. Many lives and much money could be saved if the work of hepatologists led to the development of effective diagnostic and therapeutic strategies against this growing leader of cirrhosis.

  12. [Application of iodine metabolism analysis methods in thyroid diseases].

    Science.gov (United States)

    Han, Jian-hua; Qiu, Ling

    2013-08-01

    The main physiological role of iodine in the body is to synthesize thyroid hormone. Both iodine deficiency and iodine excess can lead to severe thyroid diseases. While its role in thyroid diseases has increasingly been recognized, few relevant platforms and techniques for iodine detection have been available in China. This paper summarizes the advantages and disadvantages of currently iodine detection methods including direct titration, arsenic cerium catalytic spectrophotometry, chromatography with pulsed amperometry, colorimetry based on automatic biochemistry, inductively coupled plasma mass spectrometry, so as to optimize the iodine nutrition for patients with thyroid diseases.

  13. 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.

  14. Targeting of ECM molecules and their metabolizing enzymes and receptors for the treatment of CNS diseases

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Walmod, Peter Schledermann; Filippov, Mikhail

    2014-01-01

    Extracellular matrix (ECM) molecules, their receptors at the cell surface, and cell adhesion molecules (CAMs) involved in cell-cell or cell-ECM interactions are implicated in processes related to major diseases of the central nervous system including Alzheimer's disease (AD), epilepsy......, schizophrenia, addiction, multiple sclerosis, Parkinson's disease, and cancer. There are multiple strategies for targeting the ECM molecules and their metabolizing enzymes and receptors with antibodies, peptides, glycosaminoglycans, and other natural and synthetic compounds. ECM-targeting treatments include...

  15. Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder.

    Science.gov (United States)

    Xu, Jingshu; Begley, Paul; Church, Stephanie J; Patassini, Stefano; Hollywood, Katherine A; Jüllig, Mia; Curtis, Maurice A; Waldvogel, Henry J; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

    2016-06-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder that displays pathological characteristics including senile plaques and neurofibrillary tangles. Metabolic defects are also present in AD-brain: for example, signs of deficient cerebral glucose uptake may occur decades before onset of cognitive dysfunction and tissue damage. There have been few systematic studies of the metabolite content of AD human brain, possibly due to scarcity of high-quality brain tissue and/or lack of reliable experimental methodologies. Here we sought to: 1) elucidate the molecular basis of metabolic defects in human AD-brain; and 2) identify endogenous metabolites that might guide new approaches for therapeutic intervention, diagnosis or monitoring of AD. Brains were obtained from nine cases with confirmed clinical/neuropathological AD and nine controls matched for age, sex and post-mortem delay. Metabolite levels were measured in post-mortem tissue from seven regions: three that undergo severe neuronal damage (hippocampus, entorhinal cortex and middle-temporal gyrus); three less severely affected (cingulate gyrus, sensory cortex and motor cortex); and one (cerebellum) that is relatively spared. We report a total of 55 metabolites that were altered in at least one AD-brain region, with different regions showing alterations in between 16 and 33 metabolites. Overall, we detected prominent global alterations in metabolites from several pathways involved in glucose clearance/utilization, the urea cycle, and amino-acid metabolism. The finding that potentially toxigenic molecular perturbations are widespread throughout all brain regions including the cerebellum is consistent with a global brain disease process rather than a localized effect of AD on regional brain metabolism. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. 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...

  17. Metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Poulain, M; Doucet, M; Drapeau, V; Fournier, G; Tremblay, A; Poirier, P; Maltais, F

    2008-01-01

    Overweight and obesity have been associated with better survival in patients with chronic obstructive pulmonary disease (COPD). On the other hand, excess body weight is associated with abnormal metabolic and inflammatory profiles that define the metabolic syndrome and predispose to cardiovascular diseases. This study was undertaken to evaluate the impact of overweight and obesity on the prevalence of the metabolic syndrome and on the metabolic and inflammatory profiles in patients with COPD. Twenty-eight male patients with COPD were divided into an overweight/obese group [ n = 16, body mass index (BMI) = 33.5 +/- 4.2 kg/m(2)] and normal weight group (n = 12, BMI = 21.1 +/- 2.6 kg/m(2)). Anthropometry, pulmonary function and body composition were assessed. The metabolic syndrome was diagnosed according to waist circumference, circulating levels of triglyceride and high-density lipoprotein cholesterol levels, fasting glycemia and blood pressure. C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), leptin and adiponectin plasma levels were measured. Airflow obstruction was less severe in overweight/obese compared with normal weight patients (forced expiratory volume(1): 51 +/- 19% versus 31 +/- 12% predicted, respectively, P leptin were significantly higher in overweight/obese patients whereas the adiponectin levels were reduced in the presence of excess weight. The metabolic syndrome was frequent in overweight/obese patients with COPD. Obesity in COPD was associated with a spectrum of metabolic and inflammatory abnormalities.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Chagas disease, adipose tissue and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Fnu Nagajyothi

    2009-07-01

    Full Text Available Trypanosoma cruzi infection of the adipose tissue of mice triggers the local expression of inflammatory mediators and a reduction in the expression of the adipokine adiponectin. T. cruzi can be detected in adipose tissue by PCR 300 days post-infection. Infection of cultured adipocytes results in increased expression of cytokines and chemokines and a reduction in the expression of adiponectin and the peroxisome proliferator-activated receptor ³, both of which are negative regulators of inflammation. Infection also results in the upregulation of cyclin D1, the Notch pathway, and extracellular signal-regulated kinase and a reduction in the expression of caveolin-1. Thus, T. cruzi infection of cultured adipocytes leads to an upregulation of the inflammatory process. Since adiponectin null mice have a cardiomyopathic phenotype, it is possible that the reduction in adiponectin contributes to the pathogenesis of chagasic cardiomyopathy. Adipose tissue may serve as a reservoir for T. cruzi from which parasites can become reactivated during periods of immunosuppression. T. cruzi infection of mice often results in hypoglycemia. In contrast, hyperglycemia as observed in diabetes results in increased parasitemia and mortality. Adipose tissue is an important target tissue of T. cruzi and the infection of this tissue is associated with a profound impact on systemic metabolism, increasing the risk of metabolic syndrome.

  20. 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.

  1. The relationship between physical activity and metabolic syndrome in people with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Park, Soo Kyung; Larson, Janet L

    2014-01-01

    The prevalence of metabolic syndrome has been reported to be 20% to 50% in people with chronic obstructive pulmonary disease (COPD). Because such people are sedentary and physically inactive, they are at risk of metabolic syndrome. The extent of this problem, however, is not fully understood. This study examined the relationship of sedentary time and physical activity to metabolic syndrome and the components of metabolic syndrome in a population-based sample of people with COPD. This was a secondary analysis of existing cross-sectional data. Subjects with COPD (n = 223) were drawn from the National Health and Nutrition Examination Survey data set (2003-2006). Physical activity was measured by accelerometry. Waist circumference, triglyceride level, high-density lipoprotein cholesterol level, blood pressure, and fasting glucose level were used to describe metabolic syndrome. Descriptive and inferential statistics were used for analysis. Fifty-five percent of the sample had metabolic syndrome. No significant differences in sedentary time and level of physical activity were found in people with COPD and metabolic syndrome and people with COPD only. However, those with a mean activity count of greater than 240 counts per minute had a lower prevalence of metabolic syndrome. Waist circumference and glucose level were significantly associated with the time spent in sedentary, light, and moderate to vigorous physical activity. Metabolic syndrome is highly prevalent in people with COPD, and greater physical activity and less sedentary time are associated with lower rates of metabolic syndrome. This suggests that interventions to decrease the risk of metabolic syndrome in people with COPD should include both reducing sedentary time and increasing the time and intensity of physical activity.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  3. 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.)

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

    Science.gov (United States)

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

    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.

  5. Metabolism

    Science.gov (United States)

    ... functions: Anabolism (uh-NAB-uh-liz-um), or constructive metabolism, is all about building and storing. It ... in infants and young children. Hypothyroidism slows body processes and causes fatigue (tiredness), slow heart rate, excessive ...

  6. Metabolism

    Science.gov (United States)

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... acid phenylalanine, needed for normal growth and protein production). Inborn errors of metabolism can sometimes lead to ...

  7. Guiametabolica.org: empowerment through internet tools in inherited metabolic diseases

    Directory of Open Access Journals (Sweden)

    Armayones Manuel

    2012-08-01

    Full Text Available Abstract Web-based interventions are effective on the patient empowerment. Guiametabolica.org constitutes an interface for people involved in inherited metabolic diseases, trying to facilitate access to information and contact with professionals and other patients, offering a platform to develop support groups. Guiametabolica.org is widely considered for Spanish-speaking patients and caregivers with inherited metabolic diseases. Preliminary evaluations show changes in their habits, decrease in their senses of isolation and improvement regarding self-efficacy. Specific inherited metabolic diseases websites, especially participative websites, should be considered as a complement to more traditional clinical approaches. Their contribution lies in patient’s general well-being, without interfering with traditional care.

  8. Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease.

    Science.gov (United States)

    Jacobi, Johannes; Schnellhardt, Susanne; Opgenoorth, Mirian; Amann, Kerstin U; Küttner, Axel; Schmid, Axel; Eckardt, Kai-Uwe; Hilgers, Karl F

    2010-04-18

    Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease.

  9. 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.

  10. 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......, 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...... 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Emerging opportunities for the treatment of metabolic diseases

    DEFF Research Database (Denmark)

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

    2015-01-01

    with the heterologous pathophysiology of human obesity, renders effective medicinal intervention very difficult. Indeed, the search for the silver bullet in anti-obesity medicines has been laden with drugs of underwhelming efficacy and unacceptable side effects. This can partly be the consequence that many...... of these drug interventions have been historically directed at single molecular targets. New multi-molecular combination therapies have shown promising clinical outcomes in terms of weight loss, yet multi-functional single molecules may offer even more advantages than adjunctive co-treatments. Single molecules...... 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...

  13. Influence of obesity and metabolic disease on carotid atherosclerosis in patients with coronary artery disease (CordioPrev study)

    Science.gov (United States)

    Background: Recent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC...

  14. Testosterone effect on brain metabolism in elderly patients with Alzheimer's disease: comparing two cases at different disease stages.

    Science.gov (United States)

    Tan, R S

    2013-06-01

    To describe the effect of testosterone replacement therapy (TRT) on the brain activity of two demented, hypogonadal male patients with early and late-stage Alzheimer's disease (AD), respectively. We describe the clinical and positron emission tomography (PET) findings for two individuals, one with early stage and the other with late-stage Alzheimer's disease, before and after treatment with a topical testosterone gel. Both patients were hypogonadal at baseline. We assessed cerebral glucose metabolism (CGM) via (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). We investigated whether there are testosterone-susceptible areas within cerebral structures in patients with Alzheimer's disease. Under testosterone replacement therapy, changes in cerebral glucose metabolism were observed in both patients. Improvement in glucose uptake was observed most consistently in the parietal lobe and brainstem; decreased glucose metabolism was observed in the temporal lobe, the limbic system and the insula for these two subjects. These case reports demonstrate the potential for PET scanning to detect changes in cerebral glucose metabolism in hypogonadal men with Alzheimer's disease who are treated with testosterone. Further study will be needed to investigate the consistency and significance of these changes in terms of magnitude and brain region, and the correlation with functional changes.

  15. Metabolism of glucose in brain of patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Yokoi, Fuji; Ando, Kazuya; Iio, Masaaki.

    1984-01-01

    We examined 11 C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with 11 C-glucose (per os). 11 C-glucose was prepared from 11 CO 2 by photosynthesis. 1) No significant difference was observed in the 11 C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the 11 C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author)

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

    Science.gov (United States)

    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.

  17. Metabolic profiling of follistatin overexpression: a novel therapeutic strategy for metabolic diseases

    Directory of Open Access Journals (Sweden)

    Singh R

    2018-03-01

    Full Text Available Rajan Singh,1,2 Shehla Pervin,1,2 Se-Jin Lee,3,4 Alan Kuo,5 Victor Grijalva,6 John David,7 Laurent Vergnes,8 Srinivasa T Reddy1,6 1Department of Obstetrics and Gynecology, UCLA School of Medicine, Los Angeles, CA, USA; 2Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA; 3The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; 4Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, CT, USA; 5Department of Biology, California State University Dominguez Hills, CA, USA; 6Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA, USA; 7Department of Comparative Medicine, Pfizer Inc, San Diego, CA, USA; 8Department of Human Genetics, UCLA School of Medicine, Los Angeles, CA, USA Background: Follistatin (Fst promotes brown adipocyte characteristics in adipose tissues.Methods: Abdominal fat volume (CT scan, glucose clearance (GTT test, and metabolomics analysis (mass spectrometry of adipose tissues from Fst transgenic (Fst-Tg and wild type (WT control mice were analyzed. Oxygen consumption (Seahorse Analyzer and lipidomics (gas chromatography was analyzed in 3T3-L1 cells.Results: Fst-Tg mice show significant decrease in abdominal fat content, increased glucose clearance, improved plasma lipid profiles and significant changes in several conventional metabolites compared to the WT mice. Furthermore, overexpression of Fst in 3T3-L1 cells resulted in up regulation of key brown/beige markers and changes in lipidomics profiles. Conclusion: Fst modulates key factors involved in promoting metabolic syndrome and could be used for therapeutic intervention. Keywords: follistatin, transgenic, adipocyte, fibroblast growth factor 21, AdipoQ

  18. Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control.

    Science.gov (United States)

    Dambska, M; Labrador, E B; Kuo, C L; Weinstein, D A

    2017-08-01

    Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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

  20. 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.

  1. Metabolic network as a progression biomarker of premanifest Huntington's disease

    NARCIS (Netherlands)

    Tang, Chris C.; Feigin, Andrew; Ma, Yilong; Habeck, Christian; Paulsen, Jane S.; Leenders, Klaus L.; Teune, Laura K.; van Oostrom, Joost C. H.; Guttman, Mark; Dhawan, Vijay; Eidelberg, David

    Background. The evaluation of effective disease-modifying therapies for neurodegenerative disorders relies on objective and accurate measures of progression in at-risk individuals. Here we used a computational approach to identify a functional brain network associated with the progression of

  2. Huntington’s disease : hypothalamic, endocrine and metabolic aspects

    NARCIS (Netherlands)

    Aziz, Nasir Ahmad

    2010-01-01

    The nuclear symptoms and signs of Huntington’s disease (HD) consist of motor, cognitive and behavioural disturbances. Other less well-known, but prevalent and debilitating features of HD include unintended weight loss, sleep and circadian rhythm disturbances, as well as autonomic nervous system

  3. Insights into metabolic disease from studying genetics in isolated populations

    DEFF Research Database (Denmark)

    Zeggini, Ele; Gloyn, A L; Hansen, Torben

    2016-01-01

    variation on disease risk. Current efforts are now focused on extending this to genetic variants in the rare and low-frequency spectrum by capitalising on next-generation sequencing technologies. This review discusses the important contributions that studies in isolated populations are making to this effort...

  4. Turner′s syndrome presenting as metabolic bone disease

    Directory of Open Access Journals (Sweden)

    Sadishkumar Kamalanathan

    2012-01-01

    Full Text Available Turner′s syndrome is a genetic disorder with a complete or partial absence of one X chromosome with characteristic phenotypic features. The prevalence of renal anomalies in turner syndrome is 30-40%. However, the renal function is usually normal. We report a case of Turner′s syndrome presenting with chronic kidney disease and renal osteodystrophy.

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

    Science.gov (United States)

    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

  6. Cholesterol-lowering probiotics as potential biotherapeutics for metabolic diseases.

    Science.gov (United States)

    Kumar, Manoj; Nagpal, Ravinder; Kumar, Rajesh; Hemalatha, R; Verma, Vinod; Kumar, Ashok; Chakraborty, Chaitali; Singh, Birbal; Marotta, Francesco; Jain, Shalini; Yadav, Hariom

    2012-01-01

    Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface, incorporation of

  7. Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2012-01-01

    Full Text Available Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface

  8. Cerebral oxygen metabolism in patients with early Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, Per; Cumming, Paul; Østergaard, Karen

    2012-01-01

    AIM: Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO(2)). To test this hypothesis, we compared CMRO(2...... in spatially contiguous cortical regions in early PD, and support the hypothesis that ETC dysfunction could be a primary pathogenic mechanism in early PD....

  9. 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

  10. The study on risk factor of metabolic diseases in pancreatic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Docosahexaenoic Acid, Inflammation, and Bacterial Dysbiosis in Relation to Periodontal Disease, Inflammatory Bowel Disease, and the Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Michael F. Roizen

    2013-08-01

    Full Text Available Docosahexaenoic acid (DHA, a long-chain omega-3 polyunsaturated fatty acid, has been used to treat a range of different conditions, including periodontal disease (PD and inflammatory bowel disease (IBD. That DHA helps with these oral and gastrointestinal diseases in which inflammation and bacterial dysbiosis play key roles, raises the question of whether DHA may assist in the prevention or treatment of other inflammatory conditions, such as the metabolic syndrome, which have also been linked with inflammation and alterations in normal host microbial populations. Here we review established and investigated associations between DHA, PD, and IBD. We conclude that by beneficially altering cytokine production and macrophage recruitment, the composition of intestinal microbiota and intestinal integrity, lipopolysaccharide- and adipose-induced inflammation, and insulin signaling, DHA may be a key tool in the prevention of metabolic syndrome.

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

    Science.gov (United States)

    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.

  13. Is butyrate the link between diet, intestinal microbiota and obesity-related metabolic diseases?

    Science.gov (United States)

    Brahe, L K; Astrup, A; Larsen, L H

    2013-12-01

    It is increasingly recognized that there is a connection between diet, intestinal microbiota, intestinal barrier function and the low-grade inflammation that characterizes the progression from obesity to metabolic disturbances, making dietary strategies to modulate the intestinal environment relevant. In this context, the ability of some Gram-positive anaerobic bacteria to produce the short-chain fatty acid butyrate is interesting. A lower abundance of butyrate-producing bacteria has been associated with metabolic risk in humans, and recent studies suggest that butyrate might have an anti-inflammatory potential that can alleviate obesity-related metabolic complications, possibly due to its ability to enhance the intestinal barrier function. Here, we review and discuss the potential of butyrate as an anti-inflammatory mediator in metabolic diseases, and the potential for dietary interventions increasing the intestinal availability of butyrate. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

  14. 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

    , addition of metabolic syndrome to a multivariable model including BMI and other clinical characteristics improved the Harell C-statistic only slightly for risk of MI (comparison P = .03) but not for IHD (P = .41). CONCLUSIONS AND RELEVANCE: These findings suggest that overweight and obesity are risk......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...

  15. Metabolic Pathway Genes Associated with Susceptibility Genes to Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Heng Lu

    2018-01-01

    Full Text Available Coronary artery disease (CAD is one of the leading threats to global health. Previous research has proven that metabolic pathway disorders, such as high blood lipids and diabetes, are one of the risk factors that mostly cause CAD. However, the crosstalk between metabolic pathways and CAD was mostly studied on physiology processes by analyzing a single gene function. A canonical correlation analysis was used to identify the metabolic pathways, which were integrated as a unit to coexpress with CAD susceptibility genes, and to resolve additional metabolic factors that are related to CAD. Seven pathways, including citrate cycle, ubiquinone, terpenoid quinone biosynthesis, and N-glycan biosynthesis, were identified as an integrated unit coexpressed with CAD genes. These pathways could not be revealed as a coexpressed pathway through traditional methods as each single gene has weak correlation. Furthermore, sets of genes in these pathways were candidate markers for diagnosis and detection from patients’ serum.

  16. Aloe QDM complex enhances specific cytotoxic T lymphocyte killing in vivo in metabolic disease mice.

    Science.gov (United States)

    Lee, Youngjoo; Kim, Jiyeon; An, Jinho; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Kyungjae

    2017-03-01

    We developed spontaneous diet-induced metabolic disease in mice by feeding them a high-fat diet for 23 weeks and administered Aloe QDM complex for 16 weeks to examine its restorative effect on immune disorders and metabolic syndrome. A series of immune functional assays indicated Aloe QDM complex enhanced lymphocyte proliferation and antigen-specific immunity as determined by the restored functions of cytotoxic T lymphocytes (CTL) and IgG production. The elevated serum TNF-α level was also regulated by Aloe QDM complex treatment, which suggested its complex therapeutic potential. As for metabolic phenotypes, oral administration of Aloe QDM complex significantly improved diabetic symptoms, including high fasting glucose levels and glucose tolerance, and distinctly alleviated lipid accumulation in adipose and hepatic tissue. The simultaneous restoration of Aloe QDM complex on metabolic syndrome and host immune dysfunction, especially on the specific CTL killing was first elucidated in our study.

  17. Apolipoproteins E and CIII interact to regulate HDL metabolism and coronary heart disease risk

    DEFF Research Database (Denmark)

    Morton, Allyson M; Koch, Manja; Mendivil, Carlos O

    2018-01-01

    BACKGROUND: Subspecies of HDL contain apolipoprotein E (apoE) and/or apoCIII. Both proteins have properties that could affect HDL metabolism. The relation between HDL metabolism and risk of coronary heart disease (CHD) is not well understood. METHODS: Eighteen participants were given a bolus...... infusion of [D3]L-leucine to label endogenous proteins on HDL. HDL was separated into subspecies containing apoE and/or apoCIII and then into 4 sizes. Metabolic rates for apoA-I in HDL subspecies and sizes were determined by interactive modeling. The concentrations of apoE in HDL that contain or lack apo......CIII were measured in a prospective study in Denmark including 1,949 incident CHD cases during 9 years. RESULTS: HDL containing apoE but not apoCIII is disproportionately secreted into the circulation, actively expands while circulating, and is quickly cleared. These are key metabolic steps in reverse...

  18. 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.

  19. Combined Association of Serum Uric Acid and Metabolic Syndrome with Chronic Kidney Disease in Hypertensive Patients.

    Science.gov (United States)

    Dai, Haijiang; Lu, Shijuan; Tang, Xiaohong; Lu, Minggen; Chen, Ruifang; Chen, Zhiheng; Yang, Pingting; Liu, Chang; Zhou, Honghao; Lu, Yao; Yuan, Hong

    2016-01-01

    Chronic kidney disease (CKD) is one of the major complications of hypertension. It is not only associated with the future burden of end-stage renal disease but also affects mortality and cardiovascular outcomes caused by hypertension. To help understand the pathogenesis and early prevention of progressive CKD, this large-scale study is designed to determine the complex association between serum uric acid (SUA), metabolic syndrome and the prevalence of CKD in hypertensive patients. A total of 19,848 hypertensive subjects were enrolled in this cross-sectional study. Patients with proteinuria and/or an estimated glomerular filtration rate (eGFR) of metabolic syndrome, as well as higher levels of SUA, BMI, waist circumference (WC), SBP, DBP, TG, fasting blood glucose and lower levels of HDL-C. Compared to patients without CKD, the multivariate-adjusted odds ratios [ORs, 95% confidence interval (CI)] for CKD patients were 2.30 (2.02-2.63) for hyperuricemia, 1.21 (1.04-1.41) for abdominal obesity, 1.21 (1.06-1.38) for elevated TG, 1.29 (1.06-1.56) for low HDL-C, 1.54 (1.36-1.75) for elevated fasting glucose, and 1.49 (1.30-1.71) for metabolic syndrome. Increasing SUA levels and number of individual metabolic syndrome components were associated with an increased prevalence of CKD. Compared with patients classified in the lowest SUA categories and with ≤1 metabolic syndrome components, subjects with HUA and 4 metabolic syndrome components had a 5.77-fold increased OR for CKD based on the multivariate-adjusted analysis. Both elevated SUA and metabolic syndrome are associated with an increased prevalence of CKD in hypertensive subjects. Subjects with higher SUA and sum of individual metabolic syndrome components simultaneously have a higher prevalence of CKD. © 2016 The Author(s) Published by S. Karger AG, Basel.

  20. Roles of abnormal lipid metabolism in pathogenesis of non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    LU Ran

    2015-07-01

    Full Text Available The prevalence of non-alcoholic fatty liver disease (NAFLD keeps rising worldwide along with the increasing prevalence of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. Although most NAFLD patients present with simple steatosis of hepatocytes, some patients progress to non-alcoholic steatohepatitis, liver cirrhosis, and even cancer. In the Western world, NAFLD is the most common cause of elevated liver enzymes, and hence there has been a growing interest in this disease. Given that fat deposition in the liver is the hallmark of NAFLD, we review the roles and the underlying mechanism of disturbed lipid metabolism in the development of NAFLD and suggest that more insights into the pathogenesis of NAFLD will help develop targeted strategies for the prevention and treatment of this disease.

  1. Peroxisome Proliferator-Activated Receptor Modulation during Metabolic Diseases and Cancers: Master and Minions

    Science.gov (United States)

    Nigro, Angela; La Rosa, Valentina Lucia; Rossetti, Paola; Rapisarda, Agnese Maria Chiara; Condorelli, Rosita Angela; Corrado, Francesco; Buscema, Massimo

    2016-01-01

    The prevalence of obesity and metabolic diseases (such as type 2 diabetes mellitus, dyslipidaemia, and cardiovascular diseases) has increased in the last decade, in both industrialized and developing countries. This also coincided with our observation of a similar increase in the prevalence of cancers. The aetiology of these diseases is very complex and involves genetic, nutritional, and environmental factors. Much evidence indicates the central role undertaken by peroxisome proliferator-activated receptors (PPARs) in the development of these disorders. Due to the fact that their ligands could become crucial in future target-therapies, PPARs have therefore become the focal point of much research. Based on this evidence, this narrative review was written with the purpose of outlining the effects of PPARs, their actions, and their prospective uses in metabolic diseases and cancers. PMID:28115924

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Sozen, Erdi; Ozer, Nesrin Kartal

    2017-08-01

    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. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. 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

  5. Hot Air Treatment Induces Disease Resistance through Activating the Phenylpropanoid Metabolism in Cherry Tomato Fruit.

    Science.gov (United States)

    Wei, Yingying; Zhou, Dandan; Peng, Jing; Pan, Leiqing; Tu, Kang

    2017-09-13

    To explore the effects of hot air (HA, 38 °C for 12 h) treatment on the phenylpropanoid metabolism in cherry tomatoes, phenylpropanoid metabolite levels and the activities and expression of key enzymes were analyzed in HA-treated fruit. HA treatment enhanced phenylpropanoid metabolism, as evidenced by elevated levels of phenolics and flavonoids, higher activities of phenylalanine ammonia-lyase and cinnamate-4-hydroxylase, and upregulated expression of LeCHS, LeCHI, LeF3H, and LeFLS. Levels of several phenylpropanoid metabolites were higher after HA treatment, including p-coumaric acid, caffeic acid, chlorogenic acid, isoquercitrin, quercetin, and rutin. These metabolic changes may be related to the reduced disease incidence and smaller lesion diameters observed in HA-treated fruit inoculated with Alternaria alternata (black mold) or Botrytis cinerea (gray mold). The results suggest that HA treatment induces disease resistance by activating the phenylpropanoid pathway in cherry tomato fruit.

  6. PPARγ: A Molecular Link between systemic metabolic disease and benign prostate hyperplasia

    Science.gov (United States)

    Jiang, Ming; Strand, Douglas W.; Franco, Omar E.; Clark, Peter E.; Hayward, Simon W.

    2011-01-01

    The emergent epidemic of metabolic syndrome and its complex list of sequelae mandate a more thorough understanding of benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) in the context of systemic metabolic disease. Here we discuss the nature and origins of BPH, examine its role as a component of LUTS and review retrospective clinical studies that have drawn associations between BPH/LUTS and type II diabetes, inflammation and dyslipidemia. PPARγ signaling, which sits at the nexus of systemic metabolic disease and BPH/LUTS through its regulation of inflammation and insulin resistance is proposed as a candidate for molecular manipulation in regard to BPH/LUTS. Finally, we introduce new cell and animal models that are being used to study the consequences of obesity, diabetes and inflammation on benign prostatic growth. PMID:21645960

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Lysophosphatidic acid metabolism and elimination in cardiovascular disease

    Science.gov (United States)

    Salous, Abdelghaffar Kamal

    The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are present in human and mouse plasma at a concentration of ~0.1-1 microM and regulate physiological and pathophysiological processes in the cardiovascular system including atherothrombosis, intimal hyperplasia, and immune function, edema formation, and permeability. PPAP2B, the gene encoding LPP3, a broad activity integral membrane enzyme that terminates LPA actions in the vasculature, has a single nucleotide polymorphism that been recently associated with coronary artery disease risk. The synthesis and signaling of LPA and S1P in the cardiovascular system have been extensively studied but the mechanisms responsible for their elimination are less well understood. The broad goal of this research was to examine the role of LPP3 in the termination of LPA signaling in models of cardiovascular disease involving vascular wall cells, investigate the role of LPP3 in the elimination of plasma LPA, and further characterize the elimination of plasma LPA. The central hypothesis is that LPP3 plays an important role in attenuating the pathological responses to LPA signaling and that it mediates the elimination of exogenously applied bioactive lipids from the plasma. These hypotheses were tested using molecular biological approaches, in vitro studies, synthetic lysophospholipid mimetics, modified surgical procedures, and mass spectrometry assays. My results indicated that LPP3 played a critical role in attenuating LPA signaling mediating the pathological processes of intimal hyperplasia and vascular leak in mouse models of disease. Additionally, enzymatic inactivation of lysophospholipids by LPP and PLA enzymes in the plasma was not a primary mechanism for the rapid elimination of plasma LPA and S1P. Instead, evidence strongly suggested a transcellular uptake mechanism by hepatic non-parenchymal cells as the predominant mechanism for elimination of these molecules. These results support a model in

  9. Roles of abnormal lipid metabolism in pathogenesis of non-alcoholic fatty liver disease

    OpenAIRE

    LU Ran; HONG Tianpei

    2015-01-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) keeps rising worldwide along with the increasing prevalence of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. Although most NAFLD patients present with simple steatosis of hepatocytes, some patients progress to non-alcoholic steatohepatitis, liver cirrhosis, and even cancer. In the Western world, NAFLD is the most common cause of elevated liver enzymes, and hence there has been a growing interest in this disea...

  10. Neridronic acid for the treatment of bone metabolic diseases.

    Science.gov (United States)

    Gatti, Davide; Viapiana, Ombretta; Idolazzi, Luca; Fracassi, Elena; Adami, Silvano

    2009-10-01

    Neridronic acid (6-amino-1-idroxyesilidene-1,1-bisphosphonate) is a nitrogen-containing bisphosphonate licensed in Italy for the treatment of osteogenesis imperfecta and Paget's disease of bone. The pharmacodynamic profile is similar to that of other nitrogen-containing bisphosphonates and is characterized by its high affinity for bone tissue particularly at sites undergoing a process of remodeling. In growing children affected by osteogenesis imperfect, neridronic acid rapidly increases bone mineral density as measured by dual X-ray absortiometry and this is associated with a significant decrease in fracture cumulative number. Similar results have been obtained also in newborns ( 75% of bone turnover markers) in 95% of the patients. Neridronic acid treatment has been reported to be effective also in other skeletal diseases such as osteoporosis, algodystrophy, hypercalcemia of malignancy and bone metastasis. Neridronic acid has been developed only for parenteral use, and it is the only one used as intramuscular injection. This avoids all the limitations of oral bisphosphonates and may be offered for a home treatment with simple nursing assistance.

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

    Directory of Open Access Journals (Sweden)

    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

  12. Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen; Hansen, Tine W; Rasmussen, Susanne

    2007-01-01

    OBJECTIVES: The goal was to clarify if insulin resistance (IR) would predict cardiovascular disease (CVD) independent of the metabolic syndrome (MetSyn). BACKGROUND: Although the cause of MetSyn is not well defined, IR has been proposed to be an important cause. Only a small number of population...

  13. 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

  14. 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...

  15. 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 ...

  16. 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

  17. The future of metabolic syndrome and cardiovascular disease prevention: polyhype or polyhope?: tales from the polyera

    NARCIS (Netherlands)

    Franco, O.; Karnik, K.; Bonneux, L.G.A.

    2007-01-01

    Recently society has been witnessing the rise of a new era in the prevention and treatment of the metabolic syndrome and cardiovascular disease: the Polyera. This new era started when a promising concept – the Polypill – was introduced by Wald et al. in 2003. The Polypill is a theoretical

  18. Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn study

    NARCIS (Netherlands)

    Dekker, J.M.; Girman, C.J.; Rhodes, T.; Nijpels, M.G.A.A.M.; Stehouwer, C.D.A.; Bouter, L.M.; Heine, R.J.

    2005-01-01

    Background - Different definitions of the metabolic syndrome have been proposed. Their value in a clinical setting to assess cardiovascular disease (CVD) risk is still unclear. We compared the definitions proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP), World

  19. Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn study

    NARCIS (Netherlands)

    Dekker, J.M.; Girman, C.J.; Rhodes, T.; Nijpels, M.G.A.A.M.; Stehouwer, C.D.A.; Bouter, L.M.; Heine, R.J.

    2005-01-01

    BACKGROUND: Different definitions of the metabolic syndrome have been proposed. Their value in a clinical setting to assess cardiovascular disease (CVD) risk is still unclear. We compared the definitions proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP), World

  20. 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.

  1. 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

  2. Association between metabolic syndrome and 10-year risk of developing cardiovascular disease in a Nigerian population

    DEFF Research Database (Denmark)

    Oguoma, Victor M.; Nwose, Ezekiel U.; Skinner, Timothy C.

    2016-01-01

    Background: Prevalence of metabolic syndrome (MetS) and consequential cardiovascular disease (CVD) events are on the increase in Nigeria. The study aimed to identify the prevalence of 10-year CVD risk in a Nigerian population and assess its relationship with different indices of MetS. Method: A c...

  3. Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony

    Science.gov (United States)

    2012-01-01

    Chronic obstructive pulmonary disease, metabolic syndrome and diabetes mellitus are common and underdiagnosed medical conditions. It was predicted that chronic obstructive pulmonary disease will be the third leading cause of death worldwide by 2020. The healthcare burden of this disease is even greater if we consider the significant impact of chronic obstructive pulmonary disease on the cardiovascular morbidity and mortality. Chronic obstructive pulmonary disease may be considered as a novel risk factor for new onset type 2 diabetes mellitus via multiple pathophysiological alterations such as: inflammation and oxidative stress, insulin resistance, weight gain and alterations in metabolism of adipokines. On the other hand, diabetes may act as an independent factor, negatively affecting pulmonary structure and function. Diabetes is associated with an increased risk of pulmonary infections, disease exacerbations and worsened COPD outcomes. On the top of that, coexistent OSA may increase the risk for type 2 DM in some individuals. The current scientific data necessitate a greater outlook on chronic obstructive pulmonary disease and chronic obstructive pulmonary disease may be viewed as a risk factor for the new onset type 2 diabetes mellitus. Conversely, both types of diabetes mellitus should be viewed as strong contributing factors for the development of obstructive lung disease. Such approach can potentially improve the outcomes and medical control for both conditions, and, thus, decrease the healthcare burden of these major medical problems. PMID:23101436

  4. The Counterbalance of Skin Metabolism on Orbits and Diseases

    Directory of Open Access Journals (Sweden)

    Li-Fan Chuang

    2015-05-01

    Full Text Available Human organ functions are regulated by the nervous system. When human cells receive a message, this message is transmitted to the nervous system through a series of signal transmission processes. Skin conditions that occur after applying skin cream are closely related to signal transmission and nervous regulation. We determined the connection between signal regulation and natural rhythmic operations. The diurnal variations resulting from the earth’s rotation and indicate the relative relationships between the sympathetic nervous system and the parasympathetic nerve system. A spectrum was developed to assess neural transmission conditions by using skin signals which from Fourier transformation of the waves and established the association between the spectrum and diseases. The results could explain the relationships between the neurological illnesses and established spectrum. The objective was to promote the use of this spectrum as a new tool for conducting the nervous system tests in the future.

  5. 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.)

  6. Metabolic pathway of non-alcoholic fatty liver disease: Network properties and robustness

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2017-03-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a systematic and complex disease involving various cytokines/metabolites. In present article, we use methodology of network biology to analyze network properties of NAFLD metabolic pathway. It is found that the metabolic pathway of NAFLD is not a typical complex network with power-law degree distribution, p(x=x^(-4.4275, x>=5. There is only one connected component in the metabolic pathway. The calculated cut cytokines/metabolites of the metabolic pathway are SREBP-1c, ChREBP, ObR, AMPK, IRE1alpha, ROS, PERK, elF2alpha, ATF4, CHOP, Bim, CASP8, Bid, CxII, Lipogenic enzymes, XBP1, and FFAs. The most important cytokine/metabolite for possible network robustness is FFAs, seconded by TNF-alpha. It is concluded that FFAs is the most important cytokine/metabolite in the metabolic pathway, seconded by ROS. FFAs, LEP, ACDC, CYP2E1, and Glucose are the only cytokines/metabolites that affect others without influences from other cytokines/metabolites. Finally, the IDs matrix for identifying possible sub-networks/modules is given. However, jointly combining the results of connectedness analysis and sub-networks/modules identification, we hold that there are not significant sub-networks/modules in the pathway.

  7. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    Directory of Open Access Journals (Sweden)

    Stefano Gitto

    2016-04-01

    Full Text Available Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis.

  8. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.

    Science.gov (United States)

    Gitto, Stefano; Villa, Erica

    2016-04-02

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis.

  9. Recent Research Progress in Natural Bioactive Constituents against Lipid Metabolic Diseases.

    Science.gov (United States)

    Nie, Lirong; Song, Hang; He, Ai; Yao, Shun

    2016-01-01

    Lipid metabolic disorder refers to the dyslipidemia in the plasma. Abnormal working or lipid metabolism process leads to supernormal increase of one or multi kinds of lipids in plasma. It is a significant risk factor for many diseases and has become a serious danger to the mankind health. The clinical drugs adjusting lipid levels have a great variety in the market, side effects and adverse reactions. Meanwhile, many Chinese herbal medicines and natural medicines have the unnegligible role of regulating lipid metabolism, which become the research focus of medical workers in past decades. With advantages of fewer side effects, abundant resources and multi-target functions, terrestrial and marine bioactive constituents are proved as one of the important sources of the lead compounds in drug discovery and have been widely applied in the treatment and prevention of lipid metabolic diseases. In this paper, the recent advancements and current status of natural medicinal ingredients mainly based on lipid-lowering activities were reviewed in detail. Moreover, their bioactivity screening and important mechanisms in hyperlipemia progression were summarized and compared. It was also selectively introduced about related structural modification and new drug development on the basis of promising lead compounds. Finally, the current problems and possible prospects of natural constituents against lipid metabolism disorder in the future were discussed.

  10. Review of the pathophysiological aspects involved in urological disease associated with metabolic syndrome.

    Science.gov (United States)

    Sáenz Medina, J; Carballido Rodríguez, J

    2016-06-01

    Metabolic syndrome is a constellation of disorders that includes insulin resistance, central obesity, arterial hypertension and hyperlipidaemia. These disorders can have implications for the genitourinary apparatus. To conduct a review on the pathophysiological aspects that explain the relationship between metabolic syndrome and sexual dysfunction, lower urinary tract syndrome, prostate cancer and stone disease. We performed a qualitative, narrative literature review through a literature search on PubMed of articles published between 1997 and 2015, using the terms pathophysiology, metabolic syndrome, endothelial dysfunction, lipotoxicity, mitochondrial dysfunction, kidney stones, hypogonadism, erectile dysfunction, lower urinary tract syndrome and prostate cancer. Metabolic syndrome constitutes an established complex of symptoms, defined as the presence of insulin resistance, central obesity, hypertension and hyperlipidaemia. Endothelial dysfunction secondary to lipotoxicity generates an inflammatory state, which involves renal cell metabolism, vascularisation of the pelvis and androgen production. These facts explain the relationship between metabolic syndrome, nephrolithiasis, lower urinary tract syndrome, hypogonadism and erectile dysfunction in men. Strategies such as proper diet, regular exercise, insulin treatment, testosterone-replacement therapy, therapy with antioxidants and free-radical inhibitors and urological treatments classically used for lower urinary tract syndrome have shown promising results in this syndrome. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    Science.gov (United States)

    Moin, Shaheen; Gondal, Ghulam Murtaza; Bano, Uzma

    2008-08-01

    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. Diabetes Clinic, Fauji Foundation Hospital, Rawalpindi, from January to August 2006. 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' 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.

  12. Nutrient and immune sensing are obligate pathways in metabolism, immunity, and disease.

    Science.gov (United States)

    Iyer, Abishek; Brown, Lindsay; Whitehead, Jonathan P; Prins, Johannes B; Fairlie, David P

    2015-09-01

    The growth and survival of multicellular organisms depend upon their abilities to acquire and metabolize nutrients, efficiently store and harness energy, and sense and fight infection. Systems for sensing and using nutrients have consequently coevolved alongside systems for sensing and responding to danger signals, including pathogens, and share many of the same cell signaling proteins and networks. Diets rich in carbohydrates and fats can overload these systems, leading to obesity, metabolic dysfunction, impaired immunity, and cardiovascular disease. Excessive nutrient intake promotes adiposity, typically altering adipocyte function and immune cell distribution, both of which trigger metabolic dysfunction. Here, we discuss novel mechanistic links between metabolism and immunity that underlie metabolic dysfunction in obesity. We aim to stimulate debate about how the endocrine and immune systems are connected through autocrine, paracrine, and neuroendocrine signaling in sophisticated networks that are only now beginning to be resolved. Understanding the expression and action of signaling proteins, together with modulating their receptors or pattern recognition using agonists or antagonists, will enable rational intervention in immunometabolism that may lead to novel treatments for obesity and metabolic dysfunction. © FASEB.

  13. Histologic diagnosis of metabolic bone diseases: bone histomorphometry

    Directory of Open Access Journals (Sweden)

    L. Dalle Carbonare

    2011-09-01

    Full Text Available Histomorphometry or quantitative histology is the analysis on histologic sections of bone resorption parameters, formation and structure. It is the only technique that allows a dynamic evaluation of the activity of bone modelling after labelling with tetracycline. Moreover, the new measurement procedures through the use of the computer allow an assessment of bone microarchitecture too. Histomorphometric bone biopsy is a reliable and well-tolerated procedure. Complications are reported only in 1% of the subjects (hematoma, pain, transient neuralgia. Histomorphometry is used to exclude or confirm the diagnosis of osteomalacia. It is employed in the evaluation of bone damage associated with particular treatments (for example, anticonvulsants or in case of rare bone diseases (osteogenesis imperfecta, systemic mastocytosis. It is also an essential approach when clinical, biochemical and other diagnostic data are not consistent. Finally, it is a useful method to understand the pathophysiologic mechanisms of drugs. The bone sample is taken at the level of iliac crest under local anesthesia. It is then put into methyl-metacrilate resin where the sections are prepared for the microscopic analysis of the various histomorphometric parameters.

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

    Science.gov (United States)

    Glastras, Sarah Jean; Chen, Hui; Pollock, Carol A; Saad, Sonia

    2018-02-26

    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 and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all 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. ©2018 The Author(s).

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

    Science.gov (United States)

    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.

  16. Modes of metabolic compensation during mitochondrial disease using the Drosophila model of ATP6 dysfunction.

    Directory of Open Access Journals (Sweden)

    Alicia M Celotto

    Full Text Available Numerous mitochondrial DNA mutations cause mitochondrial encephalomyopathy: a collection of related diseases for which there exists no effective treatment. Mitochondrial encephalomyopathies are complex multisystem diseases that exhibit a relentless progression of severity, making them both difficult to treat and study. The pathogenic and compensatory metabolic changes that are associated with chronic mitochondrial dysfunction are not well understood. The Drosophila ATP6(1 mutant models human mitochondrial encephalomyopathy and allows the study of metabolic changes and compensation that occur throughout the lifetime of an affected animal. ATP6(1animals have a nearly complete loss of ATP synthase activity and an acute bioenergetic deficit when they are asymptomatic, but surprisingly we discovered no chronic bioenergetic deficit in these animals during their symptomatic period. Our data demonstrate dynamic metabolic compensatory mechanisms that sustain normal energy availability and activity despite chronic mitochondrial complex V dysfunction resulting from an endogenous mutation in the mitochondrial DNA. ATP6(1animals compensate for their loss of oxidative phosphorylation through increases in glycolytic flux, ketogenesis and Kreb's cycle activity early during pathogenesis. However, succinate dehydrogenase activity is reduced and mitochondrial supercomplex formation is severely disrupted contributing to the pathogenesis seen in ATP6(1 animals. These studies demonstrate the dynamic nature of metabolic compensatory mechanisms and emphasize the need for time course studies in tractable animal systems to elucidate disease pathogenesis and novel therapeutic avenues.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Metabolic syndrome in sub-Saharan Africa: "smaller twin" of a region's prostatic diseases?

    Science.gov (United States)

    Ejike, Chukwunonso E C C; Ezeanyika, Lawrence U S

    2008-01-01

    Prostate cancer (PC) and benign prostate hyperplasia (BPH) constitute many of the health concerns of males around the world. Prostate cancer is the major cause of death after lung cancer in men. Benign prostate hyperplasia affects most males above 40 years of age. A variety of factors, chiefly age, genetics and lifestyle, have been linked to the development of PC and BPH. The metabolic syndrome describes a chain of chronic disorders that are inter-related in aetiology, and result from unhealthy lifestyles, often due to an affluent economy. The eating of processed foods and a sedentary lifestyle apparently are status symbols among the middle and upper classes in sub-Saharan Africa. These have resulted in a surge in the disease burden of sub-Saharan Africa. This paper looks at the aetiology and prevalence of the metabolic syndrome and prostatic diseases, especially in sub-Saharan Africa. Evidence from the available literature shows that prostate disorders may be related to the metabolic syndrome. There is a likelihood that if sub-Saharan Africans keep copying the lifestyles of the developed world, especially in the direction of the nature of food items consumed, then the rising prevalence of diseases of the metabolic syndrome and the attendant prostate disorders may become very formidable healthcare "twin" problems for the region.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  2. Interventions for metabolic bone disease in children with chronic kidney disease.

    Science.gov (United States)

    Hahn, Deirdre; Hodson, Elisabeth M; Craig, Jonathan C

    2015-11-12

    Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates. This is an update of a review first published in 2010. This review aimed to examine the benefits (improved growth rates, reduced risk of bone fractures and deformities, reduction in PTH levels) and harms (hypercalcaemia, blood vessel calcification, deterioration in kidney function) of interventions (including vitamin D preparations and phosphate binders) for the prevention and treatment of metabolic bone disease in children with CKD. We searched the Cochrane Kidney and Transplant Specialised Register to 8 September 2015 through contact with the Trial's Search Co-ordinator using search terms relevant for this review. We included randomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2 to 5D. Data were assessed for study eligibility, risk of bias and extracted independently by two authors. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model. This review included 18 studies (576 children); three new studies were added for this update. Adequate sequence generation and allocation concealment were reported in 12 and 11 studies respectively. Only four studies reported blinding of children, investigators or outcome assessors. Nine studies were at low risk of attrition bias and 12 studies were at low risk of selective reporting bias.Eight different interventions were compared. Two studies compared intraperitoneal (IP) with oral calcitriol. PTH levels were significantly lower with IP compared with oral calcitriol (1 study: MD -501.00 pg/mL, 95% CI -721.54 to

  3. Considerations on pig models for appetite, metabolic syndrome and obese type 2 diabetes: From food intake to metabolic disease.

    Science.gov (United States)

    Koopmans, Sietse Jan; Schuurman, Teun

    2015-07-15

    (Mini)pigs have proven to be a valuable animal model in nutritional, metabolic and cardiovascular research and in some other biomedical research areas (toxicology, neurobiology). The large resemblance of (neuro)anatomy, the gastro-intestinal tract, body size, body composition, and the omnivorous food choice and appetite of the pig are additional reasons to select this large animal species for (preclinical) nutritional and pharmacological studies. Both humans and pigs are prone to the development of obesity and related cardiovascular diseases such as hypertension and atherosclerosis. Bad cholesterol (LDL) is high and good cholesterol (HDL) is low in pigs, like in humans. Disease-relevant pig models fill the gap between rodent models and primate species including humans. Diet-induced obese pigs show a phenotype related to the metabolic syndrome including high amounts of visceral fat, fatty organs, insulin resistance and high blood pressure. However, overt hyperglycaemia does not develop within 6 months after initiation of high sugar-fat feeding. Therefore, to accelerate the induction of obese type 2 diabetes, obese pigs can be titrated with streptozotocin, a chemical agent which selectively damages the insulin-producing pancreatic beta-cells. However, insulin is required to maintain obesity. With proper titration of streptozotocin, insulin secretion can be restrained at such a level that hyperglycaemia will be induced but lipolysis is still inhibited due to the fact that inhibition of lipolysis is more sensitive to insulin compared to stimulation of glucose uptake. This strategy may lead to a stable hyperglycaemic, non-ketotic obese pig model which remains anabolic with time without the necessity of exogenous insulin treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Brain metabolic dysfunction at the core of Alzheimer’s disease

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    de la Monte, Suzanne M.; Tong, Ming

    2015-01-01

    Growing evidence supports the concept that Alzheimer’s disease (AD) is fundamentally a metabolic disease with molecular and biochemical features that correspond with diabetes mellitus and other peripheral insulin resistance disorders. Brain insulin/IGF resistance and its consequences can readily account for most of the structural and functional abnormalities in AD. However, disease pathogenesis is complicated by the fact that AD can occur as a separate disease process, or arise in association with systemic insulin resistance diseases, including diabetes, obesity, and non-alcoholic fatty liver disease. Whether primary or secondary in origin, brain insulin/IGF resistance initiates a cascade of neurodegeneration that is propagated by metabolic dysfunction, increased oxidative and ER stress, neuro-inflammation, impaired cell survival, and dysregulated lipid metabolism. These injurious processes compromise neuronal and glial functions, reduce neurotransmitter homeostasis, and cause toxic oligomeric pTau and (amyloid beta peptide of amyloid beta precursor protein) AβPP-Aβ fibrils and insoluble aggregates (neurofibrillary tangles and plaques) to accumulate in brain. AD progresses due to: (1) activation of a harmful positive feedback loop that progressively worsens the effects of insulin resistance; and (2) the formation of ROS- and RNS-related lipid, protein, and DNA adducts that permanently damage basic cellular and molecular functions. Epidemiologic data suggest that insulin resistance diseases, including AD, are exposure-related in etiology. Furthermore, experimental and lifestyle trend data suggest chronic low-level nitrosamine exposures are responsible. These concepts offer opportunities to discover and implement new treatments and devise preventive measures to conquer the AD and other insulin resistance disease epidemics. PMID:24380887

  5. Hypogonadism as a possible link between metabolic diseases and erectile dysfunction in aging men.

    Science.gov (United States)

    Corona, Giovanni; Bianchini, Silvia; Sforza, Alessandra; Vignozzi, Linda; Maggi, Mario

    2015-01-01

    There is evidence demonstrating that sexual complaints represent the most specific symptoms associated with late onset hypogonadism, while central obesity is the most specific sign. In obese men, hypogonadism can further worsen the metabolic profile and increase abdominal fat. In addition, although hypogonadism can exacerbate obesity-associated erectile dysfunction (ED), recent data suggest that a direct contribution of fat-derived factors could be hypothesized. In particular, an animal model recently documented that fat accumulation induces several hepatic pro-inflammatory genes closely linked to corpora cavernosa endothelial dysfunction. Lifestyle modifications and weight loss are the first steps in the treatment of ED patients with obesity or metabolic diseases. In symptomatic hypogonadal men with metabolic impairment and obesity, combining the effect of testosterone substitution with lifestyle modifications could result in better outcomes.

  6. Unraveling the role of ER stress inhibitors in the context of metabolic diseases.

    Science.gov (United States)

    Sarvani, Chodisetty; Sireesh, Dornadula; Ramkumar, Kunka Mohanram

    2017-05-01

    ER stress is provoked by the accumulation of unfolded and misfolded proteins in the ER lumen leading to perturbations in ER homeostasis. ER stress activates a signaling cascade called the Unfolded Protein Response (UPR) which triggers a set of transcriptional and translational events that restore ER homeostasis, promoting cell survival and adaptation. If this adaptive response fails, a terminal UPR program commits such cells to apoptosis. Existing preclinical and clinical evidence testify that prolonged ER stress escalates the risk of several metabolic disorders including diabetes, obesity and dyslipidemia. There have been considerable efforts to develop small molecules that are capable of ameliorating ER stress. Few naturally occurring and synthetic molecules have already been demonstrated for their efficacy in abrogating ER stress in both in vitro and in vivo models of metabolic disorders. This review provides a broad overview of the molecular mechanisms of inhibition of ER stress and its association with various metabolic diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The Benefits of Exercise and Metabolic Interventions for the Prevention and Early Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Maliszewska-Cyna, Ewelina; Lynch, Madelaine; Oore, Jonathan Jordan; Nagy, Paul Michael; Aubert, Isabelle

    2017-01-01

    Alzheimer's disease (AD) is characterized by neuronal degeneration, vascular pathology and cognitive decline. Furthermore, deficits in cerebral glucose metabolism and insulin resistance are being increasingly recognized in AD. Many lifestyle-modifying approaches, including diet and exercise, have yielded promising results in modulating brain morphology and function for the prevention and early treatment of AD. This review focuses on the effects of physical exercise on rescuing cognition and limiting the progression of AD pathology. Specifically, the impact of exercise, in human and animal models of AD, on the stimulation and preservation of cognition, neurotransmission, neurogenesis, vasculature, glucose metabolism and insulin signaling is discussed. Studies have highlighted the potential of physical activity to improve overall brain health, which could delay or lessen AD-related cognitive deficits and pathology. Physical activity influences cognitive function, vascular health and brain metabolism, which taken together offers benefits for the aging population, including AD patients.

  8. Mitochondrial resetting and metabolic reprogramming in induced pluripotent stem cells and mitochondrial disease modeling.

    Science.gov (United States)

    Hsu, Yi-Chao; Chen, Chien-Tsun; Wei, Yau-Huei

    2016-04-01

    Nuclear reprogramming with pluripotency factors enables somatic cells to gain the properties of embryonic stem cells. Mitochondrial resetting and metabolic reprogramming are suggested to be key early events in the induction of human skin fibroblasts to induced pluripotent stem cells (iPSCs). We review recent advances in the study of the molecular basis for mitochondrial resetting and metabolic reprogramming in the regulation of the formation of iPSCs. In particular, the recent progress in using iPSCs for mitochondrial disease modeling was discussed. iPSCs rely on glycolysis rather than oxidative phosphorylation as a major supply of energy. Mitochondrial resetting and metabolic reprogramming thus play crucial roles in the process of generation of iPSCs from somatic cells. Neurons, myocytes, and cardiomyocytes are cells containing abundant mitochondria in the human body, which can be differentiated from iPSCs or trans-differentiated from fibroblasts. Generating these cells from iPSCs derived from skin fibroblasts of patients with mitochondrial diseases or by trans-differentiation with cell-specific transcription factors will provide valuable insights into the role of mitochondrial DNA heteroplasmy in mitochondrial disease modeling and serves as a novel platform for screening of drugs to treat patients with mitochondrial diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  10. [[GUIDELINES FOR THE PREVENTION, MONITORING AND THERAPY OF CHRONIC KIDNEY DISEASE-METABOLIC BONE DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE].

    Science.gov (United States)

    Bašić-Jukić, Nikolina; Pavlović, Draško; Šmalcelj, Ružica; Tomić-Brzac, Hrvojka; Orlic, Lidija; Radić, Josipa; Vujičić, Božidar; Lovčić, Vesna; Pavić, Eva; Klarić, Dragan; Gulin, Marijana; Spasovski, Goce; Ljutić, Dragan; Danic, Davorin; Prgomet, Drago; Resić, Halima; Ratković, Marina; Kes, Petar; Raćki, Sanjin

    2016-05-01

    Chronic kidney disease (CKD) is a systemic disease with numerous complications associated with increased morbidity and mortality. Chronic kidney disease-metabolic bone disease (CKD-MBD) starts at early stages of CKD with phosphorus accumulation and consequent initiation of numerous events that result with the development of secondary hyperparathyroidism with changes on bones and extraskeletal tissues. The most important and clinically most relevant consequences of CKD-MBD are vascular calcifications which contribute to cardiovascular mortality. Patients with the increased risk for the development of CKD-MBD should be recognized and treated. Prevention is the most important therapeutic option. The first step should be nutritional counseling with vitamin supplementation if necessary and correction of mineral status. Progression of CKD requires more intensive medicamentous treatment with the additional correction of metabolic acidosis and anemia. Renal replacement therapy should be timely initiated, with the adequate dose of dislaysis. Ideally, preemptive renal transplantion should be offered in individuals without contraindication for immunosuppressive therapy.

  11. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

    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)

  13. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Science.gov (United States)

    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

  16. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases

    Science.gov (United States)

    Ruchat, Stephanie-May; Houde, Andrée-Anne; Voisin, Grégory; St-Pierre, Julie; Perron, Patrice; Baillargeon, Jean-Patrice; Gaudet, Daniel; Hivert, Marie-France; Brisson, Diane; Bouchard, Luigi

    2013-01-01

    Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk for chronic diseases, and one promising mechanism for fetal metabolic programming is epigenetics. Therefore, we postulated that GDM exposure impacts the offspring’s methylome and used an epigenomic approach to explore this hypothesis. Placenta and cord blood samples were obtained from 44 newborns, including 30 exposed to GDM. Women were recruited at first trimester of pregnancy and followed until delivery. GDM was assessed after a 75-g oral glucose tolerance test at 24–28 weeks of pregnancy. DNA methylation was measured at > 485,000 CpG sites (Infinium HumanMethylation450 BeadChips). Ingenuity Pathway Analysis was conducted to identify metabolic pathways epigenetically affected by GDM. Our results showed that 3,271 and 3,758 genes in placenta and cord blood, respectively, were potentially differentially methylated between samples exposed or not to GDM (p-values down to 1 × 10−06; none reached the genome-wide significance levels), with more than 25% (n = 1,029) being common to both tissues. Mean DNA methylation differences between groups were 5.7 ± 3.2% and 3.4 ± 1.9% for placenta and cord blood, respectively. These genes were likely involved in the metabolic diseases pathway (up to 115 genes (11%), p-values for pathways = 1.9 × 10−13 < p < 4.0 × 10−03; including diabetes mellitus p = 4.3 × 10−11). Among the differentially methylated genes, 326 in placenta and 117 in cord blood were also associated with newborn weight. Our results therefore suggest that GDM has epigenetic effects on genes preferentially involved in the metabolic diseases pathway, with consequences on fetal growth and development, and provide supportive evidence that DNA methylation is involved in fetal metabolic programming. PMID:23975224

  17. Biconnectivity of the cellular metabolism: A cross-species study and its implication for human diseases

    Science.gov (United States)

    Kim, P.; Lee, D.-S.; Kahng, B.

    2015-01-01

    The maintenance of stability during perturbations is essential for living organisms, and cellular networks organize multiple pathways to enable elements to remain connected and communicate, even when some pathways are broken. Here, we evaluated the biconnectivity of the metabolic networks of 506 species in terms of the clustering coefficients and the largest biconnected components (LBCs), wherein a biconnected component (BC) indicates a set of nodes in which every pair is connected by more than one path. Via comparison with the rewired networks, we illustrated how biconnectivity in cellular metabolism is achieved on small and large scales. Defining the biconnectivity of individual metabolic compounds by counting the number of species in which the compound belonged to the LBC, we demonstrated that biconnectivity is significantly correlated with the evolutionary age and functional importance of a compound. The prevalence of diseases associated with each metabolic compound quantifies the compounds vulnerability, i.e., the likelihood that it will cause a metabolic disorder. Moreover, the vulnerability depends on both the biconnectivity and the lethality of the compound. This fact can be used in drug discovery and medical treatments. PMID:26490723

  18. Evaluation of the metabolism of high energy phosphates in patients with Chagas' disease.

    Science.gov (United States)

    Leme, Ana Maria Betim Paes; Salemi, Vera Maria Cury; Parga, José Rodrigues; Ianni, Bárbara Maria; Mady, Charles; Weiss, Robert G; Kalil-Filho, Roberto

    2010-08-01

    Abnormalities in myocardial metabolism have been observed in patients with heart failure of different etiologies. Magnetic resonance spectroscopy (MRS) with phosphorus-31 is a noninvasive technique that allows detection of myocardial metabolic changes. To determine the resting metabolism of high-energy phosphates in patients with Chagas' disease (CD) by MRS with phosphorus-31. We studied 39 patients with CD, 23 with preserved ventricular function (PF Group) and 16 with ventricular dysfunction (VD Group), assessed by Doppler echocardiography. MRS of the anterosseptal region was performed in 39 patients and 8 normal subjects (C Group) through a Phillips 1.5 Tesla device, obtaining the phosphocreatine/beta-adenosine triphosphate myocardial ratio (PCr/β-ATP). The levels of cardiac PCr/β-ATP were reduced in VD Group in relation to PF Group, and the latter presented reduced levels compared to C Group (VD Group: 0.89 ± 0.31 vs PF Group: 1.47 ± 0.34 vs C Group: 1.88 ± 0.08, p energy metabolism of patients with Chagas' disease, with and without systolic dysfunction. These changes were related to the severity of heart impairment.

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

    Science.gov (United States)

    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.

  20. Maternal Macronutrient Consumption and the Developmental Origins of Metabolic Disease in the Offspring

    Directory of Open Access Journals (Sweden)

    Stephanie M. Kereliuk

    2017-07-01

    Full Text Available Recent research aimed at understanding the rise in obesity and cardiometabolic disease in children suggests that suboptimal maternal nutrition conditions organ systems and physiological responses in the offspring contributing to disease development. Understanding the mechanisms by which the macronutrient composition of the maternal diet during pregnancy or lactation affects health outcomes in the offspring may lead to new maternal nutrition recommendations, disease prevention strategies and therapies that reduce the increasing incidence of cardiometabolic disease in children. Recent mechanistic animal model research has identified how excess fats and sugars in the maternal diet alter offspring glucose tolerance, insulin signaling and metabolism. Maternal nutrition appears to influence epigenetic alterations in the offspring and the programming of gene expression in key metabolic pathways. This review is focused on experimental studies in animal models that have investigated mechanisms of how maternal consumption of macronutrients affects cardiometabolic disease development in the offspring. Future research using “-omic” technologies is essential to elucidate the mechanisms of how altered maternal macronutrient consumption influences the development of disease in the offspring.

  1. 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.)

  2. 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

    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...... the technique into clinical practice. Hyperpolarized MR has the prospect of transforming diagnostic cardiology by offering new insights into cardiac disease and potentially even to contribute to personalized therapy based on a thorough understanding of the individual intracellular metabolism....

  3. The Role of Seafood Nutrients and Persistent Organic Pollutants in the Development of Metabolic Diseases

    DEFF Research Database (Denmark)

    Bernhard, Annette

    cardiometabolic risk factors. However, consumption of fish and other seafood represent a major route for exposure to persistent organic pollutants (POPs), which have been implicated as a contributing risk factor to the development of metabolic diseases. Previous risk assessments addressing POP exposure through......Metabolic diseases are on the rise and pose a major threat to global public health. Consumption of fish and other seafood and associated long-chain omega-3 poly-unsaturated fatty acids (LC n3 PUFAs) are considered an integral part of a healthy diet, with documented beneficial effects on several......HBCD exposure. Fish and fish oil as part of a high fat diet reduced hepatic lipid accumulation and improved insulin sensitivity. Furthermore, dietary fish oil reduced tissue accumulation of αHBCD in liver and adipose tissue, likely due to a combination of reducing levels of liver lipids and increasing...

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

    Science.gov (United States)

    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.

  5. Metabolic endotoxemia directly increases the proliferation of adipocyte precursors at the onset of metabolic diseases through a CD14-dependent mechanism★

    OpenAIRE

    Luche, Elodie; Cousin, Béatrice; Garidou, Lucile; Serino, Matteo; Waget, Aurélie; Barreau, Corinne; André, Mireille; Valet, Philippe; Courtney, Michael; Casteilla, Louis; Burcelin, Rémy

    2013-01-01

    International audience; Metabolic endotoxemia triggers inflammation, targets cells from the stroma-vascular fraction of adipose depots, and metabolic disease. To identify these cells we here infused mice with lipopolysaccharides and showed by FACS analyses and BrdU staining that the number of small subcutaneous adipocytes, preadipocytes and macrophages increased in wild type but not in CD14-knockout (KO) mice. This mechanism was direct since in CD14KO mice grafted subcutaneously and simultane...

  6. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    OpenAIRE

    Gitto, Stefano; Villa, Erica

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent signifi...

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

    Science.gov (United States)

    2017-09-01

    individual cell types within human adipose tissue interact to regulate adipose tissue physiology . Specifically, we have developed the molecular and...AWARD NUMBER: W81XWH-15-1-0251 TITLE: “Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA...TYPE Annual 3. DATES COVERED 1 AUG 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluation of Human Adipose Tissue Stromal

  8. Disorders of Lipid Metabolism and its Correction in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    O.O. Melnyk

    2016-04-01

    Full Text Available Chronic kidney disease — a proven risk factor of the development and progression of lipid metabolism disorders. The basis of these disorders — an increase in blood plasma cholesterol, triglycerides, low density lipoproteins and decreased levels of high density lipoproteins, apo AI and apo AII. There has been a decrease in the activity of enzymes: lipoprotein lipase, hepatic triglyceride lipase, lecithin-cholesterol acyltransferase. The use of lipid-modifying drugs — statins, fibrates, nicotinic acid was proposed.

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

    Directory of Open Access Journals (Sweden)

    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

  10. Metabolic endotoxemia directly increases the proliferation of adipocyte precursors at the onset of metabolic diseases through a CD14-dependent mechanism★

    Science.gov (United States)

    Luche, Elodie; Cousin, Béatrice; Garidou, Lucile; Serino, Matteo; Waget, Aurélie; Barreau, Corinne; André, Mireille; Valet, Philippe; Courtney, Michael; Casteilla, Louis; Burcelin, Rémy

    2013-01-01

    Metabolic endotoxemia triggers inflammation, targets cells from the stroma-vascular fraction of adipose depots, and metabolic disease. To identify these cells we here infused mice with lipopolysaccharides and showed by FACS analyses and BrdU staining that the number of small subcutaneous adipocytes, preadipocytes and macrophages increased in wild type but not in CD14-knockout (KO) mice. This mechanism was direct since in CD14KO mice grafted subcutaneously and simultaneously with fat pads from CD14KO and wild-type mice the concentration of cytokine mRNA was increased in the wild-type fat pad only. Conversely, the mRNA concentration of genes involved in glucose and lipid metabolism and the number of large adipocytes was reduced. Eventually, a pretreatment with LPS enhanced HFD-induced metabolic diseases. Altogether, these results show that metabolic endotoxemia increases the proliferation of preadipocytes through a CD14-dependent mechanism directly, without recruiting CD14-positive cells from non-adipose depot origin. This mechanism could precede the onset of metabolic diseases. PMID:24049740

  11. Metabolic endotoxemia directly increases the proliferation of adipocyte precursors at the onset of metabolic diseases through a CD14-dependent mechanism.

    Science.gov (United States)

    Luche, Elodie; Cousin, Béatrice; Garidou, Lucile; Serino, Matteo; Waget, Aurélie; Barreau, Corinne; André, Mireille; Valet, Philippe; Courtney, Michael; Casteilla, Louis; Burcelin, Rémy

    2013-01-01

    Metabolic endotoxemia triggers inflammation, targets cells from the stroma-vascular fraction of adipose depots, and metabolic disease. To identify these cells we here infused mice with lipopolysaccharides and showed by FACS analyses and BrdU staining that the number of small subcutaneous adipocytes, preadipocytes and macrophages increased in wild type but not in CD14-knockout (KO) mice. This mechanism was direct since in CD14KO mice grafted subcutaneously and simultaneously with fat pads from CD14KO and wild-type mice the concentration of cytokine mRNA was increased in the wild-type fat pad only. Conversely, the mRNA concentration of genes involved in glucose and lipid metabolism and the number of large adipocytes was reduced. Eventually, a pretreatment with LPS enhanced HFD-induced metabolic diseases. Altogether, these results show that metabolic endotoxemia increases the proliferation of preadipocytes through a CD14-dependent mechanism directly, without recruiting CD14-positive cells from non-adipose depot origin. This mechanism could precede the onset of metabolic diseases.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  13. Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease

    Directory of Open Access Journals (Sweden)

    Schmid Axel

    2010-04-01

    Full Text Available Abstract Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. Conclusions This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease.

  14. Functions of Arginase Isoforms in Macrophage Inflammatory Responses: Impact on Cardiovascular Diseases and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Zhihong eYang

    2014-10-01

    Full Text Available Macrophages play a paramount role in immunity and inflammation-associated diseases, including infections, cardiovascular diseases, obesity‐associated metabolic imbalances and cancer. Compelling evidence from studies of recent years demonstrates that macrophages are heterogeneous and undergo heterogeneous phenotypic changes in response to microenvironmental stimuli. The M1 Killer type response and the M2 Repair type response are best known, and are two extreme examples. Among other markers, inducible nitric oxide synthase (iNOS and type-I arginase (Arg-I, the enzymes that are involved in L-arginine/nitric oxide (NO metabolism, are associated with the M1 and M2 phenotype, respectively, and therefore widely used as the markers for characterization of the two macrophage phenotypes. There is also a type-II arginase (Arg-II which is expressed in macrophages and prevalently viewed as having the same function as Arg-I in the cells. In contrast to Arg-I, little information on the role of Arg‐II in macrophage inflammatory responses is available. Emerging evidence, however, suggests differential roles of Arg-I and Arg-II in regulating macrophage functions. In this article, we will review recent developments on the functional roles of the two arginase isoforms in regulation of macrophage inflammatory responses by focusing on their impact on the pathogenesis of cardiovascular diseases and metabolic disorders.

  15. Hormonal Regulation of Nitric Oxide (NO) in Cardio-metabolic Diseases.

    Science.gov (United States)

    Sudar-Milovanovic, Emina; Zafirovic, Sonja; Jovanovic, Aleksandra; Trebaljevac, Jovana; Obradovic, Milan; Cenic-Milosevic, Desanka; Isenovic, Esma R

    2017-01-01

    Nitric oxide (NO) is a potential biochemical, cardio-metabolic risk marker. The production of NO is catalyzed by different isoforms of enzymes, NO synthases (NOS). An altered NO level is associated with obesity, insulin resistance (IR), diabetes and cardiovascular diseases (CVD). Activity of NOS and NO production are regulated by various hormones under physiological and pathophysiological condition. Data used for this review were obtained by searching the electronic database [PUBMED/MEDLINE 1984 - May 2016]. Additionally, abstracts from national and international diabetes and cardiovascular related meetings were searched. The main data search terms were: nitric oxide, nitric oxide synthase, cardio-metabolic risk, obesity, diabetes, cardiovascular disease, estradiol and insulin-like growth factor-1. In this review, we summarize the recent literature data related to the regulation of endothelial NOS (eNOS), inducible (iNOS) activity/expression, and thereby NO production by the hormones: estradiol (E2), and insulin-like growth factor-1 (IGF-1). Understanding the regulation of NO production by different hormones such as E2, and IGF-1 may provide novel and useful knowledge regarding how endothelial dysfunction (ED) is linked with cardio-metabolic alterations and diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

    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.

  17. 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.

  18. Metabolic profiles of exercise in patients with McArdle disease or mitochondrial myopathy.

    Science.gov (United States)

    Delaney, Nigel F; Sharma, Rohit; Tadvalkar, Laura; Clish, Clary B; Haller, Ronald G; Mootha, Vamsi K

    2017-08-01

    McArdle disease and mitochondrial myopathy impair muscle oxidative phosphorylation (OXPHOS) by distinct mechanisms: the former by restricting oxidative substrate availability caused by blocked glycogen breakdown, the latter because of intrinsic respiratory chain defects. We applied metabolic profiling to systematically interrogate these disorders at rest, when muscle symptoms are typically minimal, and with exercise, when symptoms of premature fatigue and potential muscle injury are unmasked. At rest, patients with mitochondrial disease exhibit elevated lactate and reduced uridine; in McArdle disease purine nucleotide metabolites, including xanthine, hypoxanthine, and inosine are elevated. During exercise, glycolytic intermediates, TCA cycle intermediates, and pantothenate expand dramatically in both mitochondrial disease and control subjects. In contrast, in McArdle disease, these metabolites remain unchanged from rest; but urea cycle intermediates are increased, likely attributable to increased ammonia production as a result of exaggerated purine degradation. Our results establish skeletal muscle glycogen as the source of TCA cycle expansion that normally accompanies exercise and imply that impaired TCA cycle flux is a central mechanism of restricted oxidative capacity in this disorder. Finally, we report that resting levels of long-chain triacylglycerols in mitochondrial myopathy correlate with the severity of OXPHOS dysfunction, as indicated by the level of impaired O 2 extraction from arterial blood during peak exercise. Our integrated analysis of exercise and metabolism provides unique insights into the biochemical basis of these muscle oxidative defects, with potential implications for their clinical management.

  19. [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.

  20. Alkaline Diet and Metabolic Acidosis: Practical Approaches to the Nutritional Management of Chronic Kidney Disease.

    Science.gov (United States)

    Rodrigues Neto Angéloco, Larissa; Arces de Souza, Gabriela Cristina; Almeida Romão, Elen; Garcia Chiarello, Paula

    2017-12-05

    The kidneys play an extremely important role in maintaining the body acid-base balance by excreting nonvolatile acids and regenerating and reabsorbing bicarbonate in the kidney tubules. As the individual loses their kidney function, renal excretion of nonvolatile acid produced by metabolism of the diet is impaired, resulting in low-grade metabolic acidosis. With this in mind, it is relevant to better understand the dietary aspects related to the acid-base balance in chronic kidney disease metabolic acidosis and try to provide possible strategies for the nutritional management of these cases. The type of diet can deeply affect the body by providing acid or base precursors. Generally speaking, foods such as meat, eggs, cheese, and grains increase the production of acid in the organism, whereas fruit and vegetables are alkalizing. On the other hand, milk is considered neutral as well as fats and sugars, which have a small effect on acid-base balance. The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products. Thus metabolic acidosis may be exacerbated by a contemporary Western diet, which delivers a high nonvolatile acid load. The remaining acid is neutralized or stored within the body. Bone and muscle are lost to neutralize the acid and serum bicarbonate falls. Early studies suggest that lowering the dietary acid load with a reduced protein content and vegetable proteins replacements, associated with an increase in fruits and vegetables intake can improve the metabolic parameters of acidosis, preserve bone and muscle, and slow the glomerular filtration rate decline. More studies focusing on the effects of controlled dietary interventions among chronic kidney disease patients are needed to determining the optimal target for nutritional therapy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    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

  2. Association between the metabolic syndrome and chronic kidney disease in Chinese adults.

    Science.gov (United States)

    Chen, Jing; Gu, Dongfeng; Chen, Chung-Shiuan; Wu, Xigui; Hamm, L Lee; Muntner, Paul; Batuman, Vecihi; Lee, Chien-Hung; Whelton, Paul K; He, Jiang

    2007-04-01

    The metabolic syndrome is a common risk factor for cardiovascular and chronic kidney disease (CKD) in Western populations. We examined the relationship between the metabolic syndrome and risk of CKD in Chinese adults. A cross-sectional survey was conducted in a nationally representative sample of 15 160 Chinese adults aged 35-74 years. The metabolic syndrome was defined as the presence of three or more of the following risk factors: elevated blood pressure, low high density lipoprotein (HDL)-cholesterol, high triglycerides, elevated plasma glucose and abdominal obesity. CKD was defined as an estimated glomerular filtration ratecreatinine was defined as >or=1.14 mg/dl in men and >or=0.97 mg/dl in women (>or=95th percentile of serum creatinine in Chinese men and women aged 35-44 years without hypertension or diabetes, respectively). The multivariate-adjusted odds ratios [95% confidence interval (CI)] of CKD and elevated serum creatinine in participants with compared to those without the metabolic syndrome were 1.64 (1.16, 2.32) and 1.36 (1.07, 1.73), respectively. Compared to participants without any components of the metabolic syndrome, the multivariate-adjusted odds ratios (95% CI) of CKD were 1.51 (1.02, 2.23), 1.50 (0.97, 2.32), 2.13 (1.30, 3.50) and 2.72 (1.50, 4.93) for those with 1, 2, 3, and 4 or 5 components, respectively. The corresponding multivariate-adjusted odds ratios (95% CI) of elevated serum creatinine were 1.11 (0.88, 1.40), 1.39 (1.07, 2.04), 1.47 (1.06, 2.04) and 2.00 (1.32, 3.03), respectively. These findings suggest that the metabolic syndrome might be an important risk factor for CKD in Chinese adults.

  3. Profile of Cardiovascular Risk Factors in Patients with Coronary Heart Disease, Normal and Impaired Carbohydrate Metabolism

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    І.V. Cherniavska

    2015-11-01

    Full Text Available The aim of research was to conduct the comparative analysis of the profile of cardiovascular risk factors in patients with coronary heart disease (CHD and normal either impaired carbohydrate metabolism. Materials and methods. One hundred and forty two patients were observed. In order to estimate the rate of different forms of CHD depending on the state of carbohydrate metabolism such groups were formed: the first group consisted of 83 patients with type 2 diabetes mellitus (DM, the second group involved 34 patients with impaired glucose tolerance (IGT, the third group consisted of 25 patients with normal carbohydrate metabolism. The ischemic changes of myocardium were detected by ambulatory ECG monitoring with the obligatory achievement of submaximal heart rate during the research. Results. Silent myocardial ischemia was educed in 19 (22.9 % patients with type 2 DM, in 3 (8.8 % persons with IGT and in 2 (8.0 % patients with normal carbohydrate metabolism. Smoking, burdened heredity, violation in the haemostatic system more often occurred in the group of patients with type 2 DM and silent myocardial ischemia in comparison with the patients with type 2 DM without CHD. The profile of general population cardiovascular risk factors in patients with CHD and type 2 DM belongs to the most unfavorable. At the same time for patients with early violations of carbohydrate metabolism and normal carbohydrate metabolism such profile statistically does not differentiate meaningfully. Conclusions. Patients with type 2 DM and silent myocardial ischemia as compared to patients with type 2 DM without CHD have more expressed violations of indexes of general population cardiovascular risk factors for certain.

  4. Wilson′s disease - A rare cause of renal tubular acidosis with metabolic bone disease

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    D. K. S. Subrahmanyam

    2014-01-01

    Full Text Available We report a 16-year-old boy who presented with weakness of lower limbs. He was diagnosed to have Wilson′s disease, renal tubular acidosis and osteoporosis. Screening of siblings showed that his younger sister was also affected by the disease.

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

    Science.gov (United States)

    Kimani-Murage, Elizabeth W; Kahn, Kathleen; Pettifor, John M; Tollman, Stephen M; Dunger, David B; Gómez-Olivé, Xavier F; Norris, Shane A

    2010-03-25

    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. 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 or = 25 and > or = 30 kg/m2 for overweight and obesity respectively were used for those > or = 18 years. Waist circumference cut-offs of > or = 94 cm for males and > or = 80 cm for females and waist-to-height ratio of 0.5 for both sexes were used to determine metabolic disease risk in adolescents. 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. 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 relates to changes in nutrition

  6. 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

  7. Relations between subclinical disease markers and type 2 diabetes, metabolic syndrome, and incident cardiovascular disease: the Jackson Heart Study.

    Science.gov (United States)

    Xanthakis, Vanessa; Sung, Jung Hye; Samdarshi, Tandaw E; Hill, Alethea N; Musani, Solomon K; Sims, Mario; Ghraibeh, Kamel A; Liebson, Philip R; Taylor, Herman A; Vasan, Ramachandran S; Fox, Ervin R

    2015-06-01

    The presence of subclinical disease measures has been directly associated with the development of cardiovascular disease (CVD) in whites. African Americans (AAs) in the U.S. are at higher risk of CVD compared with non-Hispanic whites; however, data on the prevalence of subclinical disease measures in AAs and their association to CVD remain unclear and may explain the higher CVD risk in this group. We evaluated 4,416 participants attending the first examination of the Jackson Heart Study (mean age 54 years; 64% women) with available subclinical disease measures. There were 1,155 participants (26%) with subclinical disease, defined as the presence of one or more of the following: peripheral arterial disease, left ventricular hypertrophy, microalbuminuria, high coronary artery calcium (CAC) score, and low left ventricular ejection fraction. In cross-sectional analyses using multivariable-adjusted logistic regression, participants with metabolic syndrome (MetS) or diabetes (DM) had higher odds of subclinical disease compared with those without MetS and DM (odds ratios 1.55 [95% CI 1.30-1.85] and 2.86 [95% CI 2.32-3.53], respectively). Furthermore, the presence of a high CAC score and left ventricular hypertrophy were directly associated with the incidence of CVD (265 events) in multivariable-adjusted Cox proportional hazards regression models (P disease (P disease, which in turn translated into a greater risk of CVD, especially in people with MetS and DM. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Mitochondrial function and autophagy: integrating proteotoxic, redox, and metabolic stress in Parkinson's disease.

    Science.gov (United States)

    Zhang, Jianhua; Culp, Matilda Lillian; Craver, Jason G; Darley-Usmar, Victor

    2018-01-17

    Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and needs to be further examined to help develop biomarkers for PD severity and prognosis. It is now becoming clear that multiple hits on metabolic and signaling pathways are likely to exacerbate PD pathogenesis. Indeed, data obtained from genetic and genome association studies have implicated interactive contributions of genes controlling protein quality control and metabolism. For example, loss of key proteins that are responsible for clearance of dysfunctional mitochondria through a process called mitophagy has been found to cause PD, and a significant proportion of genes associated with PD encode proteins involved in the autophagy-lysosomal pathway. In this review, we highlight the evidence for the targeting of mitochondria by proteotoxic, redox and metabolic stress, and the role autophagic surveillance in maintenance of mitochondrial quality. Furthermore, we summarize the role of α-synuclein, leucine-rich repeat kinase 2, and tau in modulating mitochondrial function and autophagy. Among the stressors that can overwhelm the mitochondrial quality control mechanisms, we will discuss 4-hydroxynonenal and nitric oxide. The impact of autophagy is context depend and as such can have both beneficial and detrimental effects. Furthermore, we highlight the potential of targeting mitochondria and autophagic function as an integrated therapeutic strategy and the emerging contribution of the microbiome to PD susceptibility. © 2018 International Society for Neurochemistry.

  11. 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.)

  12. 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

  13. 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.).

  14. Developmental programming of metabolic diseases – a review of studies on experimental animal models

    Directory of Open Access Journals (Sweden)

    Iwona Piotrowska

    2014-06-01

    Full Text Available Growth and development in utero is a complex and dynamic process that requires interaction between the mother organism and the fetus. The delivery of macro – and micronutrients, oxygen and endocrine signals has crucial importance for providing a high level of proliferation, growth and differentiation of cells, and a disruption in food intake not only has an influence on the growth of the fetus, but also has negative consequences for the offspring’s health in the future. Diseases that traditionally are linked to inappropriate life style of adults, such as type 2 diabetes, obesity, and arterial hypertension, can be “programmed” in the early stage of life and the disturbed growth of the fetus leads to the symptoms of the metabolic syndrome. The structural changes of some organs, such as the brain, pancreas and kidney, modifications of the signaling and metabolic pathways in skeletal muscles and in fatty tissue, epigenetic mechanisms and mitochondrial dysfunction are the basis of the metabolic disruptions. The programming of the metabolic disturbances is connected with the disruption in the intrauterine environment experienced in the early and late gestation period. It causes the changes in deposition of triglycerides, activation of the hormonal “stress axis” and disturbances in the offspring’s glucose tolerance. The present review summarizes experimental results that led to the identification of the above-mentioned links and it underlines the role of animal models in the studies of this important concept.

  15. Predictors of ischaemic heart disease in a Malaysian population with the metabolic syndrome.

    Science.gov (United States)

    Yeow, T P; Khir, A S; Ismail, A A-S; Ismail, I S; Kamarul Imran, M; Khalid, B A K; Kamaruddin, N A; Azwany, Y N; Mustafa, N; Osman, A; Md Isa, S H; Bebakar, W M W; Nazaimoon, W M W

    2012-11-01

    Cardiovascular disease is the foremost cause of mortality in Malaysia but little is known about the prevalence of the metabolic syndrome and its associations with other known cardiovascular risk markers. We undertook a population-based study to examine these. For the study, 4341 subjects were selected using a multistage stratified sampling method. Subjects were interviewed for personal and past medical history. Biomedical markers and anthropometric indices were measured. The metabolic syndrome was defined using the harmonized criteria. The associations between the metabolic syndrome and cardiovascular risk markers, including high-sensitivity C-reactive protein, microalbuminuria and HbA(1c) were examined. The prevalence of the metabolic syndrome was 42.5%. Subjects with the metabolic syndrome are significantly more likely to have higher BMI (> 25 kg/m(2)), HbA(1c) [≥ 42 mmol/mol (6.0%)], LDL (≥ 2.6 mmol/l), elevated albumin:creatinine ratio (> 2.5 μg/mmol creatinine for men, 3.5 μg/mmol creatinine for women) and high-sensitivity C-reactive protein (> 3 mg/l); odds ratio 5.48, 6.14, 1.44, 3.68 and 1.84, respectively, P creatinine ratio and high-sensitivity C-reactive protein are strong predictors for the presence of a higher number of positive criteria of the metabolic syndrome. HbA(1c) > 48 mmol/mol (6.5%) is associated with increased relative risk of elevated albumin:creatinine ratio, high-sensitivity C-reactive protein and LDL (relative risk 3.10, 2.46 and 1.65 respectively, P metabolic syndrome in Malaysia. Our study revealed a strong relationship between risk markers of elevated BMI, HbA(1c), LDL, albumin:creatinine ratio and high-sensitivity C-reactive protein with the presence of the metabolic syndrome, putting them at a statistically high risk for cardiovascular mortality. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  16. 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.

  17. Clinical significance of metabolic syndrome and carotid intima-media thickness in Behҫet’s disease patients: Relation to disease activity

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    Iman El-Gazzar

    2017-07-01

    Conclusion: Metabolic syndrome is an important co-morbidity in BD patients and measuring the IMT is essential to avoid an increase in flares or the consequent development of cardiovascular diseases or renal impairment.

  18. 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)

  19. Mechanisms of metabolic memory and renal hypoxia as a therapeutic target in diabetic kidney disease.

    Science.gov (United States)

    Hirakawa, Yosuke; Tanaka, Tetsuhiro; Nangaku, Masaomi

    2017-05-01

    Diabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is under discussion. Although the term DKD was originally defined as 'kidney disease specific to diabetes,' DKD frequently means chronic kidney disease with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction as a result of nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end-products, deoxyribonucleic acid methylation, histone modifications and non-coding ribonucleic acid including micro ribonucleic acid. Regardless of the presence of diabetes mellitus, the final common pathway in chronic kidney disease is chronic kidney hypoxia, which influences epigenetic processes, including deoxyribonucleic acid methylation, histone modification, and conformational changes in micro ribonucleic acid and chromatin. Therefore, hypoxia and oxidative stress are appropriate targets of therapies against DKD. Prolyl hydroxylase domain inhibitor enhances the defensive mechanisms against hypoxia. Bardoxolone methyl protects against oxidative stress, and can even reverse impaired renal function; a phase 2 trial with considerable attention to heart complications is currently ongoing in Japan. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  20. The gut-blood barrier permeability - A new marker in cardiovascular and metabolic diseases?

    Science.gov (United States)

    Ufnal, Marcin; Pham, Kinga

    2017-01-01

    Recent studies suggest that blood-borne metabolites of gut microbiota, such as trimethylamine N-oxide (TMAO) are involved in the aetiology of cardiovascular diseases and may serve as markers of cardiovascular risk. To enter the bloodstream the microbiota-derived molecules need to pass the gut-blood barrier (GBB). The GBB plays an important role in maintaining organism homeostasis. It is a complex multi-layer system which determines the absorption of nutrients, water and many other substances. The integrity and permeability of the GBB may be impaired in numerous diseases including gastrointestinal, metabolic and cardiovascular diseases. Here, we propose that the evaluation of the GBB permeability may have a significant diagnostic potential in cardiovascular and metabolic diseases. Second, we suggest that the GBB permeability is a variable that confounds diagnostic value of new gut microbiota-derived biomarkers such as TMAO. Therefore, cardiovascular risk assessment requires the evaluation of both TMAO and the GBB permeability. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  2. Functional and metabolic disorders in celiac disease: new implications for nutritional treatment.

    Science.gov (United States)

    Farnetti, Sara; Zocco, Maria Assunta; Garcovich, Matteo; Gasbarrini, Antonio; Capristo, Esmeralda

    2014-11-01

    Celiac disease (CD) is a chronic disease causing the inflammation of the proximal small intestine, in genetically predisposed individuals. This is triggered by the consumption of the gluten protein and the side effects of the disease are mitigated by a lifelong gluten-free diet (GFD) treatment. The predominant consequence of CD is malnutrition due to malabsorption (with diarrhea, weight loss, nutritional deficiencies, and altered blood parameters), especially in patients who do not show strict adherence to GFD treatment. Recent evidence shows that, despite a lifelong GFD, some functional disorders persist, such as compromised gallbladder function and motility, exocrine pancreatic insufficiency, increased gut permeability, small-intestinal bowel overgrowth, nonalcoholic fatty liver disease (NAFLD), lactose intolerance, and milk allergy. These abnormalities may predispose to the occurrence of overweight and obesity even in CD patients. This review focuses on the principal functional and metabolic disorders in both treated and untreated CD, ranging from alterations of the gastrointestinal system to impaired glucose and lipid metabolism and insulin secretion with the aim of providing new implications beyond a GFD, for an ad hoc nutrition treatment in these patients.

  3. Alzheimer's disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration.

    Science.gov (United States)

    Rojas-Gutierrez, Eduardo; Muñoz-Arenas, Guadalupe; Treviño, Samuel; Espinosa, Blanca; Chavez, Raúl; Rojas, Karla; Flores, Gonzalo; Díaz, Alfonso; Guevara, Jorge

    2017-06-26

    Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles. Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome, and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage. Accumulating evidence suggests that AD is closely related to a dysfunction of both insulin signaling and glucose metabolism in the brain, leading to an insulin-resistant brain state. Four drugs are currently used for this pathology: Three FDA-approved cholinesterase inhibitors and one NMDA receptor antagonist. However, wide varieties of antioxidants are promissory to delay or prevent the symptoms of AD and may help in treating the disease. Therefore, therapeutic efforts to achieve attenuation of oxidative stress could be beneficial in AD treatment, attenuating Aβ-induced neurotoxicity and improve neurological outcomes in AD. The term inflammaging characterizes a widely accepted paradigm that aging is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses in the absence of overt infection, and is a highly significant risk factor for both morbidity and mortality in the elderly. © 2017 Wiley Periodicals, Inc.

  4. Association of sleep quality components and wake time with metabolic syndrome: The Qazvin Metabolic Diseases Study (QMDS), Iran.

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    Zohal, Mohammadali; Ghorbani, Azam; Esmailzadehha, Neda; Ziaee, Amir; Mohammadi, Zahrasadat

    2017-11-01

    The aim of this study was to determine the association of sleep quality and sleep quantity with metabolic syndrome in Qazvin, Iran. this cross sectional study was conducted in 1079 residents of Qazvin selected by multistage cluster random sampling method in 2011. Metabolic syndrome was defined according to the criteria proposed by the national cholesterol education program third Adult treatment panel. Sleep was assessed using the Pittsburgh sleep quality index (PSQI). A logistic regression analysis was used to examine the association of sleep status and metabolic syndrome. Mean age was 40.08±10.33years. Of 1079, 578 (52.2%) were female, and 30.6% had metabolic syndrome. The total global PSQI score in the subjects with metabolic syndrome was significantly higher than subjects without metabolic syndrome (6.30±3.20 vs. 5.83±2.76, P=0.013). In logistic regression analysis, sleep disturbances was associated with 1.388 fold increased risk of metabolic syndrome after adjustment for age, gender, and body mass index. Sleep disturbances component was a predictor of metabolic syndrome in the present study. More longitudinal studies are necessary to understand the association of sleep quality and its components with metabolic syndrome. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  5. Is age a risk factor for liver disease and metabolic alterations in ataxia Telangiectasia patients?

    Science.gov (United States)

    Paulino, Talita Lemos; Rafael, Marina Neto; Hix, Sonia; Shigueoka, David Carlos; Ajzen, Sergio Aron; Kochi, Cristiane; Suano-Souza, Fabíola Isabel; da Silva, Rosangela; Costa-Carvalho, Beatriz T; Sarni, Roseli O S

    2017-08-04

    Ataxia telangiectasia (A-T) is a neurodegenerative disease that leads to mitochondrial dysfunction and oxidative stress. Insulin resistance (IR), type 2 diabetes and the risk for development of cardiovascular disease was recently associated as an extended phenotype of the disease. We aimed to assess IR; liver involvement; carotid intima-media thickness (cIMT) and metabolic alterations associated to cardiovascular risk in A-T patients, and relate them with age. Glucose metabolism alterations were found in 54.6% of the patients. Hepatic steatosis was diagnosed in 11/17 (64.7%) A-T patients. AST/ALT ratio > 1 was observed in 10/17 (58.8%). A strong positive correlation was observed between insulin sum concentrations with ALT (r = 0.782, p < 0.004) and age (r = 0.818, p = 0.002). Dyslipidemia was observed in 55.5% of the patients. The apolipoprotein (Apo-B)/ApoA-I ratio (r = 0.619; p < 0.01), LDL/HDL-c (r = 0.490; p < 0.05) and the Apo-B levels (r = 0.545; p < 0.05) were positively correlated to cIMT. Metabolic disorders implicated in cardiovascular and liver diseases are frequently observed in adolescent A-T patients and those tend to get worse as they become older. Therefore, nutritional intervention and the use of drugs may be necessary.

  6. Dietary Regulation of Histone Acetylases and Deacetylases for the Prevention of Metabolic Diseases

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    Jiyoung Lee

    2012-11-01

    Full Text Available Age-related diseases such as type 2 diabetes, cardiovascular disease, and cancer involve epigenetic modifications, where accumulation of minute changes in the epigenome over time leads to disease manifestation. Epigenetic changes are influenced by life style and diets. This represents an avenue whereby dietary components could accelerate or prevent age-related diseases through their effects on epigenetic modifications. Histone acetylation is an epigenetic modification that is regulated through the opposing action of histone acetylases (HATs and deacetylases (HDACs. These two families of enzymes play critical roles in metabolic processes and their dysregulation is associated with pathogenesis of several diseases. Dietary components, such as butyrate, sulforaphane, and curcumin, have been shown to affect HAT and HDAC activity, and their health benefits are attributed, at least in part, to epigenetic modifications. Given the decades that it takes to accumulate epigenetic changes, it is unlikely that pharmaceuticals could undo epigenetic changes without side effects. Therefore, long term consumption of dietary components that can alter the epigenome could be an attractive means of disease prevention. The goal of this review is to highlight the roles of diets and food components in epigenetic modifications through the regulation of HATs and HDACs for disease prevention.

  7. Trust Your Gut: Galvanizing Nutritional Interest in Intestinal Cholesterol Metabolism for Protection Against Cardiovascular Diseases

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    Jiyoung Lee

    2013-01-01

    Full Text Available Recent studies have demonstrated that the intestine is a key target organ for overall health and longevity. Complementing these studies is the discovery of the trans-intestinal cholesterol efflux pathway and the emerging role of the intestine in reverse cholesterol transport. The surfacing dynamics of the regulation of cholesterol metabolism in the intestine provides an attractive platform for intestine-specific nutritional intervention strategies to lower blood cholesterol levels for protection against cardiovascular diseases. Notably, there is mounting evidence that stimulation of pathways associated with calorie restriction may have a large effect on the regulation of cholesterol removal by the intestine. However, intestinal energy metabolism, specifically the idiosyncrasies surrounding intestinal responses to energy deprivation, is poorly understood. The goal of this paper is to review recent insights into cholesterol regulation by the intestine and to discuss the potential for positive regulation of intestine-driven cholesterol removal through the nutritional induction of pathways associated with calorie restriction.

  8. Studies on prevention of obesity, metabolic syndrome, diabetes, cardiovascular diseases and cancer by tea

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    Chung Shu Yang

    2018-01-01

    Full Text Available Tea, a popular beverage made from leaves of the plant Camellia sinensis, has been studied extensively in recent decades for its beneficial health effects in the prevention of obesity, metabolic syndrome, diabetes, cancer, and other diseases. Whereas these beneficial effects have been convincingly demonstrated in most laboratory studies, results from human studies have not been consistent. Some studies demonstrated that weight reduction, alleviation of metabolic syndrome and risk reduction in diabetes were only observed in individuals who consume 3–4 cups of tea (600–900 mg tea catechins or more daily. This chapter reviews some of these studies, the possible mechanisms of actions of tea constituents, and the challenges in extrapolating laboratory studies to human situations.

  9. [GENETIC AND METABOLIC URGENCIES IN THE NEONATAL INTENSIVE CARE UNIT: MAPLE SYRUP URINE DISEASE].

    Science.gov (United States)

    Páez Rojas, Paola Liliana; Suarez Obando, Fernando

    2015-07-01

    Maple syrup urine disease (MSUD) is a hereditary disorder of branched chain amino/keto acid metabolism, caused by a decreased activity of the branched-chain alpha- ketoacid dehydrogenase complex (BCKAD), which leads to abnormal elevated plasma concentrations of branched-chain amino acids (BCAAs) clinically manifested as a heavy burden for Central Nervous system. The toxic accumulation of substrates promotes the development of a severe and rapidly progressive neonatal encephalopathy if treatment is not immediately given. This disorder has a specific medical management in acute phase in order to minimize mortality and morbidity. For all those reasons, it is important to include the MSUD as a possible diagnosis in a encephalopathic newborn. We present a colombian newborn with classical MSUD with fatal outcome as an example of metabolic emergency and a differential diagnosis in the encephalopathic newborn. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  10. Brain energy metabolism and dopaminergic function in Huntington's disease measured in vivo using positron emission tomography

    International Nuclear Information System (INIS)

    Leenders, K.L.; Frackowiak, R.S.; Quinn, N.; Marsden, C.D.

    1986-01-01

    A 48-year-old man with typical Huntington's disease was investigated with computed tomography (CT) and positron emission tomography. Regional cerebral blood flow, oxygen extraction, oxygen and glucose utilization, L-Dopa uptake, and dopamine (D2) receptor binding were measured using several positron-labelled tracers. CT showed slight atrophy of the head of caudate but no cortical atrophy, although distinct frontal lobe dysfunction was present on psychometric testing. Oxygen and glucose metabolism and cerebral blood flow were decreased in the striata and to a lesser extent in frontal cortex. Cerebral blood flow was in the low normal range throughout the remainder of the brain. A normal metabolic ratio was found in all regions, since the changes in glucose utilization paralleled those in oxygen consumption. The capacity of the striatum to store dopamine as assessed by L-[ 18 F]-fluorodopa uptake was normal, but dopamine (D2) receptor binding was decreased when compared to normal subjects

  11. Metabolic therapy of multimorbid patients with arterial hypertension and inflammatory diseases of a parodentium

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    Yu. A. Sycheva

    2015-01-01

    Full Text Available AH is accompanied by deep metabolic and functional violations in organism tissue, including also the parodentium. The special attention is drawn by efficiency of the metabolic preparations possessing multimodal actions and allowing carrying out therapy of a number of states. The preparation of L-carnitine which is a perspective remedy for patients with AH associated with Inflammatory Deseased of Parodentium belongs to such means. In work studying of clinical efficiency and mechanisms action of L-carnitine in patients with AH and inflammatory diseases of parodentium was carried out. 70 patients with AH associated with IPD were divided into groups by way of simple randomization: a group with inclusion of a L-carnitine into the treatment and a control group, receiving only standard therapy. In the conducted research high antioxidant activity of the preparation is confirmed and the effect of L-carnitine normalizing tissue microcirculation is noted.

  12. 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

  13. The state of blood lymphocyte metabolism in Graves' disease patients in the treatment course

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    S G Shagarova

    2010-09-01

    Full Text Available This article is about the research of the blood lymphocyte metabolism in 35 women with Graves' disease (GD. The definition of thyroid (fO4, O3, thyro1tropic hormones, antibodies against thyroid peroxidase and blood lymphocyte NAD(P1dependent dehydrogenases was spent before the beginning of treatment and later 1 and 3 months receip1 tion of thiamazolc. The thyroid hormones concen1tration in GD patients is come to normal after 3 months of treat1 ment. The lympho1cyte metabolism is characterized by the increase level of macromolecular synthesis and antiox1 idant ability in cells, high efficiency malate1aspartate shuttle, and the increase level amino1acid exchange in GD patients throughout all period of re1search. Also in GD patients it is broken endocrine regulation of lymphocyte me1 tabolism, one point the correlation reduction between thyroid hormones concentra1tion and enzyme indicators.

  14. Potential role of uric acid in metabolic syndrome, hypertension, kidney injury, and cardiovascular diseases: is it time for reappraisal?

    Science.gov (United States)

    Soltani, Zohreh; Rasheed, Kashaf; Kapusta, Daniel R; Reisin, Efrain

    2013-06-01

    Elevated serum uric acid concentration is a common laboratory finding in subjects with metabolic syndrome/obesity, hypertension, kidney disease and cardiovascular events. Hyperuricemia has been attributed to hyperinsulinemia in metabolic syndrome and to decreased uric acid excretion in kidney dysfunction, and is not acknowledged as a main mediator of metabolic syndrome, renal disease, and cardiovascular disorder development. However, more recent investigations have altered this traditional view and shown, by providing compelling evidence, to support an independent link between hyperuricemia and increased risk of metabolic syndrome, diabetes, hypertension, kidney disease and cardiovascular disorders. However, despite these new findings, controversy regarding the exact role of uric acid in inducing these diseases remains to be unfolded. Furthermore, recent data suggest that the high-fructose diet in the United State, as a major cause of hyperuricemia, may be contributing to the metabolic syndrome/obesity epidemic, diabetes, hypertension, kidney disease and cardiovascular disorder. Our focus in this review is to discuss the available evidence supporting a role for uric acid in the development of metabolic syndrome, hypertension, renal disease, and cardiovascular disorder; and the potential pathophysiology mechanisms involved.

  15. 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.

  16. The metabolic profile of a rat model of chronic kidney disease

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    Yohei Tanada

    2017-05-01

    Full Text Available Background The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD with cardiorenal syndrome (CRS induced by prolonged hypertension. Methods We used inbred male Dahl salt-sensitive (DS rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group or a 0.3% NaCl diet as controls (low-salt; LS group. We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney. Results DS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA cycle, decreased. Conclusions DS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.

  17. 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

  18. A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease.

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    Adeeba Ahmed

    Full Text Available Non alcoholic fatty liver disease (NAFLD is the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH and cirrhosis. The potential role of glucocorticoids (GC in the pathogenesis of NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol (F from inactive cortisone (E (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1, or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR.In vitro studies defined 11β-HSD1 expression in normal and NASH liver samples. We then characterised hepatic cortisol metabolism in 16 patients with histologically proven NAFLD compared to 32 obese controls using gas chromatographic analysis of 24 hour urine collection and plasma cortisol generation profile following oral cortisone.In patients with steatosis 5αR activity was increased, with a decrease in hepatic 11β-HSD1 activity. Total cortisol metabolites were increased in this group consistent with increased GC production rate. In contrast, in patients with NASH, 11β-HSD1 activity was increased both in comparison to patients with steatosis, and controls. Endorsing these findings, 11β-HSD1 mRNA and immunostaining was markedly increased in NASH patients in peri septal hepatocytes and within CD68 positive macrophages within inflamed cirrhotic septa.Patients with hepatic steatosis have increased clearance and decreased hepatic regeneration of cortisol and we propose that this may represent a protective mechanism to decrease local GC availability to preserve hepatic metabolic phenotype. With progression to NASH, increased 11β-HSD1 activity and consequent cortisol regeneration may

  19. A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease.

    Science.gov (United States)

    Ahmed, Adeeba; Rabbitt, Elizabeth; Brady, Theresa; Brown, Claire; Guest, Peter; Bujalska, Iwona J; Doig, Craig; Newsome, Philip N; Hubscher, Stefan; Elias, Elwyn; Adams, David H; Tomlinson, Jeremy W; Stewart, Paul M

    2012-01-01

    Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH) and cirrhosis. The potential role of glucocorticoids (GC) in the pathogenesis of NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol (F) from inactive cortisone (E) (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1), or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR). In vitro studies defined 11β-HSD1 expression in normal and NASH liver samples. We then characterised hepatic cortisol metabolism in 16 patients with histologically proven NAFLD compared to 32 obese controls using gas chromatographic analysis of 24 hour urine collection and plasma cortisol generation profile following oral cortisone. In patients with steatosis 5αR activity was increased, with a decrease in hepatic 11β-HSD1 activity. Total cortisol metabolites were increased in this group consistent with increased GC production rate. In contrast, in patients with NASH, 11β-HSD1 activity was increased both in comparison to patients with steatosis, and controls. Endorsing these findings, 11β-HSD1 mRNA and immunostaining was markedly increased in NASH patients in peri septal hepatocytes and within CD68 positive macrophages within inflamed cirrhotic septa. Patients with hepatic steatosis have increased clearance and decreased hepatic regeneration of cortisol and we propose that this may represent a protective mechanism to decrease local GC availability to preserve hepatic metabolic phenotype. With progression to NASH, increased 11β-HSD1 activity and consequent cortisol regeneration may serve to

  20. 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

  1. 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.

  2. Metabolic Abnormalities of Erythrocytes as a Risk Factor for Alzheimer's Disease

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    Elena A. Kosenko

    2018-01-01

    Full Text Available Alzheimer's disease (AD is a slowly progressive, neurodegenerative disorder of uncertain etiology. According to the amyloid cascade hypothesis, accumulation of non-soluble amyloid β peptides (Aβ in the Central Nervous System (CNS is the primary cause initiating a pathogenic cascade leading to the complex multilayered pathology and clinical manifestation of the disease. It is, therefore, not surprising that the search for mechanisms underlying cognitive changes observed in AD has focused exclusively on the brain and Aβ-inducing synaptic and dendritic loss, oxidative stress, and neuronal death. However, since Aβ depositions were found in normal non-demented elderly people and in many other pathological conditions, the amyloid cascade hypothesis was modified to claim that intraneuronal accumulation of soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, is the first step of a fatal cascade in AD. Since a characteristic reduction of cerebral perfusion and energy metabolism occurs in patients with AD it is suggested that capillary distortions commonly found in AD brain elicit hemodynamic changes that alter the delivery and transport of essential nutrients, particularly glucose and oxygen to neuronal and glial cells. Another important factor in tissue oxygenation is the ability of erythrocytes (red blood cells, RBC to transport and deliver oxygen to tissues, which are first of all dependent on the RBC antioxidant and energy metabolism, which finally regulates the oxygen affinity of hemoglobin. In the present review, we consider the possibility that metabolic and antioxidant defense alterations in the circulating erythrocyte population can influence oxygen delivery to the brain, and that these changes might be a primary mechanism triggering the glucose metabolism disturbance resulting in neurobiological changes observed in the AD brain, possibly related to impaired cognitive function. We also discuss the possibility of using

  3. Selective processing and metabolism of disease-causing mutant prion proteins.

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    Aarthi Ashok

    2009-06-01

    Full Text Available Prion diseases are fatal neurodegenerative disorders caused by aberrant metabolism of the cellular prion protein (PrP(C. In genetic forms of these diseases, mutations in the globular C-terminal domain are hypothesized to favor the spontaneous generation of misfolded PrP conformers (including the transmissible PrP(Sc form that trigger downstream pathways leading to neuronal death. A mechanistic understanding of these diseases therefore requires knowledge of the quality control pathways that recognize and degrade aberrant PrPs. Here, we present comparative analyses of the biosynthesis, trafficking, and metabolism of a panel of genetic disease-causing prion protein mutants in the C-terminal domain. Using quantitative imaging and biochemistry, we identify a misfolded subpopulation of each mutant PrP characterized by relative detergent insolubility, inaccessibility to the cell surface, and incomplete glycan modifications. The misfolded populations of mutant PrPs were neither recognized by ER quality control pathways nor routed to ER-associated degradation despite demonstrable misfolding in the ER. Instead, mutant PrPs trafficked to the Golgi, from where the misfolded subpopulation was selectively trafficked for degradation in acidic compartments. Surprisingly, selective re-routing was dependent not only on a mutant globular domain, but on an additional lysine-based motif in the highly conserved unstructured N-terminus. These results define a specific trafficking and degradation pathway shared by many disease-causing PrP mutants. As the acidic lysosomal environment has been implicated in facilitating the conversion of PrP(C to PrP(Sc, our identification of a mutant-selective trafficking pathway to this compartment may provide a cell biological basis for spontaneous generation of PrP(Sc in familial prion disease.

  4. Educational inequalities in the metabolic syndrome and coronary heart disease among middle-aged men and women.

    Science.gov (United States)

    Silventoinen, Karri; Pankow, James; Jousilahti, Pekka; Hu, Gang; Tuomilehto, Jaakko

    2005-04-01

    Previous studies have shown socioeconomic inequalities in the metabolic syndrome and coronary heart disease (CHD), but it is not known whether educational disparities in the metabolic syndrome explain educational inequalities in CHD. We investigated this question in a prospective study of middle-aged men and women. Baseline data were collected in 1992 in Finland from 864 men and 1045 women aged 45-64 years without history of CHD. A total of 113 new CHD cases were identified by the end of 2001. Logistic and Cox regression models were used in data analysis. The metabolic syndrome defined by NCEP criteria was less prevalent in subjects with university education (21% in men and 14% in women) compared with basic level education (41% and 27%, respectively). Adjusting for health behavioural factors had only a slight effect on the educational gradient in the metabolic syndrome. An educational gradient in CHD incidence was clear [hazard ratio (HR) = 0.67 95% confidence interval (CI) 0.48-0.94, men and women combined]. Adjustment for the metabolic syndrome attenuated this gradient only slightly, but when individual components of the metabolic syndrome were included as covariates the attenuation was more substantial (HR = 0.73 95% CI 0.52-1.04). Educational differences in the metabolic syndrome and CHD incidence are clear. Metabolic risk factors explain the gradient in CHD incidence partly, but only when they are treated as independent risk factors. Screening for the metabolic syndrome alone is not sufficient to account for socioeconomic inequalities in cardiovascular disease.

  5. 8-year retrospective analysis of intravenous arginine therapy for acute metabolic strokes in pediatric mitochondrial disease.

    Science.gov (United States)

    Ganetzky, Rebecca D; Falk, Marni J

    2018-03-01

    Intravenous (IV) arginine has been reported to ameliorate acute metabolic stroke symptoms in adult patients with Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like Episodes (MELAS) syndrome, where its therapeutic benefit is postulated to result from arginine acting as a nitric oxide donor to reverse vasospasm. Further, reduced plasma arginine may occur in mitochondrial disease since the biosynthesis of arginine's precursor, citrulline, requires ATP. Metabolic strokes occur across a wide array of primary mitochondrial diseases having diverse molecular etiologies that are likely to share similar pathophysiologic mechanisms. Therefore, IV arginine has been increasingly used for the acute clinical treatment of metabolic stroke across a broad mitochondrial disease population. We performed retrospective analysis of a large cohort of subjects who were under 18 years of age at IRB #08-6177 study enrollment and had molecularly-confirmed primary mitochondrial disease (n = 71, excluding the common MELAS m.3243A>G mutation). 9 unrelated subjects in this cohort received acute arginine IV treatment for one or more stroke-like episodes (n = 17 total episodes) between 2009 and 2016 at the Children's Hospital of Philadelphia. Retrospectively reviewed data included subject genotype, clinical symptoms, age, arginine dosing, neuroimaging (if performed), prophylactic therapies, and adverse events. Genetic etiologies of subjects who presented with acute metabolic strokes included 4 mitochondrial DNA (mtDNA) pathogenic point mutations, 1 mtDNA deletion, and 4 nuclear gene disorders. Subject age ranged from 19 months to 23 years at the time of any metabolic stroke episode (median, 8 years). 3 subjects had recurrent stroke episodes. 70% of subjects were on prophylactic arginine or citrulline therapy at the time of a stroke-like episode. IV arginine was initiated on initial presentation in 65% of cases. IV arginine was given for 1-7 days (median, 1 day). A

  6. The effect of insulin resistance on amygdale glucose metabolism alterations in experimental Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ya. V. Gorina

    2017-01-01

    Full Text Available Purpose. Glucose metabolism is tightly regulated in the brain. Aberrant glucose metabolism is an important feature of neurodegenerative diseases, as inAlzheimer’s disease. The transport of glucose to the cell membrane is realized through the activity of insulin-regulated aminopeptidase (IRAP which controls transfer of glucose transporter to the plasma membrane. IRAP is considered as one of the key markers of insulin resistance in Alzheimer’s disease. However, the question of the mechanism of the action of the IRAP remains open. The aim of the study was to study the effect of IRAP expression on cells of the neuronal and glial lineage, glucose transporter (GLUT4 expression in the brain amygdala on emotional memory in animals with experimental Alzheimer’s disease.Materials and methods. The study was performed with two experimental models of Alzheimer’s disease in mice. The experimental group was mice of the CD1 line, males aged 4 months (Alzheimer’s disease model with the intra-hippocampal administration of beta-amyloid 1-42 (1 µl bilaterally in the CA1 area. The control group was mice of the CD1 line, males aged 4 months (sham-operated animals with the intrahippocampal administration of Phosphate buffered salin (1 µl bilaterally in the CA1. The genetic model of Alzheimer’s disease is the B6SLJ-Tg line mice (APPSwFlLon, PSEN1*M146L*L286V 6799Vas, males aged 4 months. The control group consisted of C57BL/6xSJL mice, males aged 4 months. Evaluation of emotional memory was carried out using “Fear conditioning” protocol. Expression of molecule-markers of insulin-resistance in the amygdala was studied by immunohistochemistry followed by confocal microscopy.Results. Aberrant associative learning and emotional memory was revealed in animals with an experimental model of Alzheimer’s disease. A decrease (p ≤ 0,05 of IRAP expression on cells of neuronal and glial nature, associated with GLUT4 down-regulation was detected in amygdala of

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Clinical significance of markers of collagen metabolism in rheumatic mitral valve disease.

    Science.gov (United States)

    Banerjee, Tanima; Mukherjee, Somaditya; Ghosh, Sudip; Biswas, Monodeep; Dutta, Santanu; Pattari, Sanjib; Chatterjee, Shelly; Bandyopadhyay, Arun

    2014-01-01

    Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. It is a major public health concern in developing countries. In RHD, mostly the valves get affected. The present study investigated whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression. This is a case control study comprising 118 subjects. It included 77 cases and 41 healthy controls. Cases were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), total Matrix Metalloproteinase-1(MMP-1) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) were assessed. Histopathology studies were performed on excised mitral valve leaflets. A p value 459 ng/mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Histopathology analysis revealed inflammation, scarring, neovascularisation and extensive leaflet fibrosis in diseased mitral valve. Levels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis.

  9. Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases

    International Nuclear Information System (INIS)

    Androutsopoulos, Vasilis P.; Kanavouras, Konstantinos; Tsatsakis, Aristidis M.

    2011-01-01

    Organophosphate pesticides are a class of compounds that are widely used in agricultural and rural areas. Paraoxonase 1 (PON1) is a phase-I enzyme that is involved in the hydrolysis of organophosphate esters. Environmental poisoning by organophosphate compounds has been the main driving force of previous research on PON1 enzymes. Recent discoveries in animal models have revealed the important role of the enzyme in lipid metabolism. However although PON1 function is well established in experimental models, the contribution of PON1 in neurodegenerative diseases remains unclear. In this minireview we summarize the involvement of PON1 genotypes in the occurrence of Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. A brief overview of latest epidemiological studies, regarding the two most important PON1 coding region polymorphisms PON1-L55M and PON1-Q192R is presented. Positive and negative associations of PON1 with disease occurrence are reported. Notably the MM and RR alleles contribute a risk enhancing effect for the development of some neurodegenerative diseases, which may be explained by the reduced lipoprotein free radical scavenging activity that may give rise to neuronal damage, through distinct mechanism. Conflicting findings that fail to support this postulate may represent the human population ethnic heterogeneity, different sample size and environmental parameters affecting PON1 status. We conclude that further epidemiological studies are required in order to address the exact contribution of PON1 genome in combination with organophosphate exposure in populations with neurodegenerative diseases.

  10. Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Androutsopoulos, Vasilis P. [Center of Toxicology Science and Research, University of Crete, Heraklion, Crete (Greece); Kanavouras, Konstantinos [Laboratory of Neurological Sciences, University of Crete, Heraklion, Crete (Greece); Tsatsakis, Aristidis M., E-mail: aris@med.uoc.gr [Center of Toxicology Science and Research, University of Crete, Heraklion, Crete (Greece)

    2011-11-15

    Organophosphate pesticides are a class of compounds that are widely used in agricultural and rural areas. Paraoxonase 1 (PON1) is a phase-I enzyme that is involved in the hydrolysis of organophosphate esters. Environmental poisoning by organophosphate compounds has been the main driving force of previous research on PON1 enzymes. Recent discoveries in animal models have revealed the important role of the enzyme in lipid metabolism. However although PON1 function is well established in experimental models, the contribution of PON1 in neurodegenerative diseases remains unclear. In this minireview we summarize the involvement of PON1 genotypes in the occurrence of Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. A brief overview of latest epidemiological studies, regarding the two most important PON1 coding region polymorphisms PON1-L55M and PON1-Q192R is presented. Positive and negative associations of PON1 with disease occurrence are reported. Notably the MM and RR alleles contribute a risk enhancing effect for the development of some neurodegenerative diseases, which may be explained by the reduced lipoprotein free radical scavenging activity that may give rise to neuronal damage, through distinct mechanism. Conflicting findings that fail to support this postulate may represent the human population ethnic heterogeneity, different sample size and environmental parameters affecting PON1 status. We conclude that further epidemiological studies are required in order to address the exact contribution of PON1 genome in combination with organophosphate exposure in populations with neurodegenerative diseases.

  11. Control of metabolism and signaling of simple bioactive sphingolipids: Implications in disease.

    Science.gov (United States)

    Gangoiti, Patricia; Camacho, Luz; Arana, Lide; Ouro, Alberto; Granado, Maria H; Brizuela, Leyre; Casas, Josefina; Fabriás, Gemma; Abad, José Luis; Delgado, Antonio; Gómez-Muñoz, Antonio

    2010-10-01

    Simple bioactive sphingolipids include ceramide, sphingosine and their phosphorylated forms sphingosine 1-phosphate and ceramide 1-phosphate. These molecules are crucial regulators of cell functions. In particular, they play important roles in the regulation of angiogenesis, apoptosis, cell proliferation, differentiation, migration, and inflammation. Decoding the mechanisms by which these cellular functions are regulated requires detailed understanding of the signaling pathways that are implicated in these processes. Most importantly, the development of inhibitors of the enzymes involved in their metabolism may be crucial for establishing new therapeutic strategies for treatment of disease. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Stevia rebaudiana Bertoni: A Natural Alternative for Treating Diseases Associated with Metabolic Syndrome.

    Science.gov (United States)

    Carrera-Lanestosa, Areli; Moguel-Ordóñez, Yolanda; Segura-Campos, Maira

    2017-10-01

    Stevia rebaudiana (SR) is often used by the food industry due to its steviol glycoside content, which is a suitable calorie-free sweetener. Further, both in vitro and in vivo studies indicate that these glycosides and the extracts from SR have pharmacological and therapeutic properties, including antioxidant, antimicrobial, antihypertensive, antidiabetic, and anticancer. This work reviews the antiobesity, antihyperglycemic, antihypertensive, and antihyperlipidemic effects of the majority of glycosides and aqueous/alcoholic extracts from the leaves, flowers, and roots of the SR. These compounds can serve as a natural and alternative treatment for diseases that are associated with metabolic syndrome, thus contributing to health promotion.

  13. 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

    of highly organised, hierarchical systems within the body. Elucidating their genetic basis is difficult when they are considered in isolation but even more difficult if their interrelationships with each other are brought into play. Not least of the problems is the lack of adequate and consistent...... 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...

  14. Unusual case of metabolic bone disease in a common marmoset (Callithrix jacchus)

    International Nuclear Information System (INIS)

    Hatt, J.M.; Sainsbury, A.W.

    1998-01-01

    Metabolic bone disease was diagnosed in an 11-month-old female common marmoset (Callithrix jacchus). It was depressed, reluctant to move, and was cachectic and small for its age. Laboratory findings included anaemia, azotaemia and an inverse calcium to phosphorus ratio. The radiological findings showed simultaneous signs of osteomalacia and soft-tissue calcification. There was decreased bone density with lytic areas in the pelvis and femur, and severe bilateral nephrocalcinosis. Postmortem examination revealed marked focal dystrophic calcification of the epi- and myocardium. Calcium and vitamin D3 deficiency (nutritional secondary hyperparathyroidism) was the most likely cause of the osteomalacia

  15. Dysregulation of multiple facets of glycogen metabolism in a murine model of Pompe disease.

    Directory of Open Access Journals (Sweden)

    Kristin M Taylor

    Full Text Available Pompe disease, also known as glycogen storage disease (GSD type II, is caused by deficiency of lysosomal acid α-glucosidase (GAA. The resulting glycogen accumulation causes a spectrum of disease severity ranging from a rapidly progressive course that is typically fatal by 1 to 2 years of age to a slower progressive course that causes significant morbidity and early mortality in children and adults. The aim of this study is to better understand the biochemical consequences of glycogen accumulation in the Pompe mouse. We evaluated glycogen metabolism in heart, triceps, quadriceps, and liver from wild type and several strains of GAA(-/- mice. Unexpectedly, we observed that lysosomal glycogen storage correlated with a robust increase in factors that normally promote glycogen biosynthesis. The GAA(-/- mouse strains were found to have elevated glycogen synthase (GS, glycogenin, hexokinase, and glucose-6-phosphate (G-6-P, the allosteric activator of GS. Treating GAA(-/- mice with recombinant human GAA (rhGAA led to a dramatic reduction in the levels of glycogen, GS, glycogenin, and G-6-P. Lysosomal glycogen storage also correlated with a dysregulation of phosphorylase, which normally breaks down cytoplasmic glycogen. Analysis of phosphorylase activity confirmed a previous report that, although phosphorylase protein levels are identical in muscle lysates from wild type and GAA(-/- mice, phosphorylase activity is suppressed in the GAA(-/- mice in the absence of AMP. This reduction in phosphorylase activity likely exacerbates lysosomal glycogen accumulation. If the dysregulation in glycogen metabolism observed in the mouse model of Pompe disease also occurs in Pompe patients, it may contribute to the observed broad spectrum of disease severity.

  16. NAFLD in the absence of metabolic syndrome: different epidemiology, pathogenetic mechanisms, risk factors for disease progression?

    Science.gov (United States)

    Yilmaz, Yusuf

    2012-02-01

    Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that have been associated with an increased risk of developing nonalcoholic fatty liver disease (NAFLD). Insulin resistance and central obesity are the key components of MetS, ultimately leading to liver fat accumulation and the subsequent development of necroinflammatory liver injury. However, the origin and nature of the metabolic stressors responsible for stimulating the progression of simple steatosis to nonalcoholic steatohepatitis (NASH) remain to be clearly identified. In addition, epidemiologic research on the association between MetS and NAFLD has provided only limited information to guide the development of targeted interventions, in particular, nutrition and pharmacologic prevention programs. This review summarizes the evidence supporting the proposal that NAFLD is not invariably associated with the presence of MetS, and mechanisms other than insulin resistance may contribute to the chronic inflammatory processes that underpin the development of liver fat accumulation and the subsequent architectural distortion of the liver. A special focus is given to increased hemoglobin as a risk factor for the development of NAFLD in the absence of MetS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Acetazolamide therapy for hypochloremic metabolic alkalosis in pediatric patients with heart disease.

    Science.gov (United States)

    Moffett, Brady S; Moffett, Tiffany I; Dickerson, Heather A

    2007-01-01

    Pediatric patients with heart disease are often treated with high doses of diuretics, which can lead to hypochloremic metabolic alkalosis. There are no data in children regarding the efficacy and safety of acetazolamide to treat hypochloremic metabolic alkalosis. Patients from January 2004 to June 2005 who received acetazolamide were identified. Inclusion criteria were: age less than 18 years, being a cardiology patient, diuretics use, and had received a 3-day course of acetazolamide. Demographic information was collected along with serum electrolytes, serum creatinine/blood urea nitrogen, urine output, pH, acid-base excess, concurrent medications, cardiac lesion/surgery, and incidence of adverse effects. Efficacy of acetazolamide was determined by comparing variables before and after the 3-day course. Statistical comparisons were made using Student's t-test. A total of 28 patients were identified, 7 of whom received oral acetazolamide, 21 intravenous acetazolamide. Patients were a median of 2.5 (range, 0.3-20) months of age, and 57% (17/28) were female. Seventy-one percent of the cohort received acetazolamide after cardiac surgery. There was no significant difference in any electrolyte, blood urea nitrogen, or serum creatinine from baseline, except for serum bicarbonate, which decreased (36.2 +/- 4.6 vs. 30.9 +/- 4.5 mmol/L, P metabolic alkalosis.

  18. Metabolic and Kidney Diseases in the Setting of Climate Change, Water Shortage, and Survival Factors.

    Science.gov (United States)

    Johnson, Richard J; Stenvinkel, Peter; Jensen, Thomas; Lanaspa, Miguel A; Roncal, Carlos; Song, Zhilin; Bankir, Lise; Sánchez-Lozada, Laura G

    2016-08-01

    Climate change (global warming) is leading to an increase in heat extremes and coupled with increasing water shortage, provides a perfect storm for a new era of environmental crises and potentially, new diseases. We use a comparative physiologic approach to show that one of the primary mechanisms by which animals protect themselves against water shortage is to increase fat mass as a means for providing metabolic water. Strong evidence suggests that certain hormones (vasopressin), foods (fructose), and metabolic products (uric acid) function as survival signals to help reduce water loss and store fat (which also provides a source of metabolic water). These mechanisms are intricately linked with each other and stimulated by dehydration and hyperosmolarity. Although these mechanisms were protective in the setting of low sugar and low salt intake in our past, today, the combination of diets high in fructose and salty foods, increasing temperatures, and decreasing available water places these survival signals in overdrive and may be accelerating the obesity and diabetes epidemics. The recent discovery of multiple epidemics of CKD occurring in agricultural workers in hot and humid environments may represent harbingers of the detrimental consequences of the combination of climate change and overactivation of survival pathways. Copyright © 2016 by the American Society of Nephrology.

  19. 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.

  20. Transcriptomic effects of depleted uranium on acetylcholine and cholesterol metabolisms in Alzheimer's disease model

    International Nuclear Information System (INIS)

    Lestaevel, Ph.; Bensoussan, H.; Racine, R.; Airault, F.; Gourmelon, P.; Souidi, M.

    2011-01-01

    Some heavy metals, or aluminium, could participate in the development of Alzheimer disease (AD). Depleted uranium (DU), another heavy metal, modulates the cholinergic system and the cholesterol metabolism in the brain of rats, but without neurological disorders. The aim of this study was to determine what happens in organisms exposed to DU that will/are developing the AD. This study was thus performed on a transgenic mouse model for human amyloid precursor protein (APP), the Tg2576 strain. The possible effects of DU through drinking water (20 mg/L) over an 8-month period were analyzed on acetylcholine and cholesterol metabolisms at gene level in the cerebral cortex. The mRNA levels of choline acetyl transferase (ChAT) vesicular acetylcholine transporter (VAChT) and ATP-binding cassette transporter A1 (ABC A1) decreased in control Tg2576 mice in comparison with wild-type mice (respectively -89%, -86% and -44%, p < 0.05). Chronic exposure of Tg2576 mice to DU increased mRNA levels of ChAT (+189%, p < 0.05), VAChT (+120%, p < 0.05) and ABC A1 (+52%, p < 0.05) compared to control Tg2576 mice. Overall, these modifications of acetylcholine and cholesterol metabolisms did not lead to increased disturbances that are specific of AD, suggesting that chronic DU exposure did not worsen the pathology in this experimental model. (authors)

  1. Voxel-based comparison of brain glucose metabolism between patients with Cushing's disease and healthy subjects

    Directory of Open Access Journals (Sweden)

    Shuai Liu

    2018-01-01

    Full Text Available Cognitive impairment and psychiatric symptoms are common in patients with Cushing's disease (CD owing to elevated levels of glucocorticoids. Molecular neuroimaging methods may help to detect changes in the brain of patients with CD. The aim of this study was to investigate the characteristics of brain metabolism and its association with serum cortisol level in CD. We compared brain metabolism, as measured using [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, between 92 patients with CD and 118 normal subjects on a voxel-wise basis. Pearson correlation was performed to evaluate the association between cerebral FDG uptake and serum cortisol level in patients with CD. We demonstrated that certain brain regions in patients with CD showed significantly increased FDG uptake, including the basal ganglia, anteromedial temporal lobe, thalamus, precentral cortex, and cerebellum. The clusters that demonstrated significantly decreased uptake were mainly located in the medial and lateral frontal cortex, superior and inferior parietal lobule, medial occipital cortex, and insular cortex. The metabolic rate of the majority of these regions was found to be significantly correlated with the serum cortisol level. Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up.

  2. The Severity of Fatty Liver Disease Relating to Metabolic Abnormalities Independently Predicts Coronary Calcification

    International Nuclear Information System (INIS)

    Lee, Ying-Hsiang; Wu, Yih-Jer; Liu, Chuan-Chuan; Hou, Charles Jia-Yin; Yeh, Hung-I.; Tsai, Cheng-Ho; Shih, Shou-Chuan; Hung, Chung-Lieh

    2011-01-01

    Background. Nonalcoholic fatty liver disease (NAFLD) is one of the metabolic disorders presented in liver. The relationship between severity of NAFLD and coronary atherosclerotic burden remains largely unknown. Methods and Materials. We analyzed subjects undergoing coronary calcium score evaluation by computed tomography (MDCT) and fatty liver assessment using abdominal ultrasonography. Framingham risk score (FRS) and metabolic risk score (MRS) were obtained in all subjects. A graded, semiquantitative score was established to quantify the severity of NAFLD. Multivariate logistic regression analysis was used to depict the association between NAFLD and calcium score. Results. Of all, 342 participants (female: 22.5%, mean age: 48.7 ± 7.0 years) met the sufficient information rendering detailed analysis. The severity of NAFLD was positively associated with MRS (X 2 = 6.12, trend P < 0.001) and FRS (X 2 = 5.88, trend P < 0.001). After multivariable adjustment for clinical variables and life styles, the existence of moderate to severe NAFLD was independently associated with abnormal calcium score (P < 0.05). Conclusion. The severity of NAFLD correlated well with metabolic abnormality and was independently predict coronary calcification beyond clinical factors. Our data suggests that NAFLD based on ultrasonogram could positively reflect the burden of coronary calcification

  3. 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

  4. Cerebral metabolic correlates of attention networks in Alzheimer's Disease: A study of the Stroop.

    Science.gov (United States)

    Melrose, Rebecca J; Young, Stephanie; Weissberger, Gali H; Natta, Laura; Harwood, Dylan; Mandelkern, Mark; Sultzer, David L

    2017-11-01

    Patients with Alzheimer's Disease (AD) show difficulties with attention. Cognitive neuroscience models posit that attention can be broken down into alerting, orienting, and executive networks. We used the Stroop Color-Word test to interrogate the neural correlates of attention deficits in AD. We hypothesized that the Word, Color, and Color-Word conditions of the Stroop would all tap into the alerting and orienting networks. The Color-Word condition would additionally tap into the executive network. A ratio of Color-Word to Color naming performance would isolate the executive network from the others. To identify the neural underpinnings of attention in AD we correlated performance on the Stroop with brain metabolic activity. Sixty-six patients with probable AD completed [ 18 F] fluorodeoxyglucose PET scanning and neuropsychological testing. Analysis was conducted with SPM12 (p<0.001 uncorrected, extent threshold 50 voxels). Performance on the Word, Color, and Color-Word conditions directly correlated with metabolic rate in right inferior parietal lobules/intraparietal sulci. The Color-Word/Color ratio revealed associations with metabolic rate in right medial prefrontal cortex and insula/operculum. Overall findings were largely consistent with the hypothesized neuroanatomical substrates of the alerting, orienting, and executive networks. As such, attention deficits in AD reflect compromise to multiple large-scale networks. Published by Elsevier Ltd.

  5. Dealing with Stress: Defective Metabolic Adaptation in Chronic Obstructive Pulmonary Disease Pathogenesis.

    Science.gov (United States)

    Michaeloudes, Charalambos; Bhavsar, Pankaj K; Mumby, Sharon; Chung, Kian Fan; Adcock, Ian M

    2017-11-01

    The mitochondrion is the main site of energy production and a hub of key signaling pathways. It is also central in stress-adaptive response due to its dynamic morphology and ability to interact with other organelles. In response to stress, mitochondria fuse into networks to increase bioenergetic efficiency and protect against oxidative damage. Mitochondrial damage triggers segregation of damaged mitochondria from the mitochondrial network through fission and their proteolytic degradation by mitophagy. Post-translational modifications of the mitochondrial proteome and nuclear cross-talk lead to reprogramming of metabolic gene expression to maintain energy production and redox balance. Chronic obstructive pulmonary disease (COPD) is caused by chronic exposure to oxidative stress arising from inhaled irritants, such as cigarette smoke. Impaired mitochondrial structure and function, due to oxidative stress-induced damage, may play a key role in causing COPD. Deregulated metabolic adaptation may contribute to the development and persistence of mitochondrial dysfunction in COPD. We discuss the evidence for deregulated metabolic adaptation and highlight important areas for investigation that will allow the identification of molecular targets for protecting the COPD lung from the effects of dysfunctional mitochondria.

  6. Alzheimer's disease and natural cognitive aging may represent adaptive metabolism reduction programs

    Directory of Open Access Journals (Sweden)

    Reser Jared

    2009-02-01

    Full Text Available Abstract The present article examines several lines of converging evidence suggesting that the slow and insidious brain changes that accumulate over the lifespan, resulting in both natural cognitive aging and Alzheimer's disease (AD, represent a metabolism reduction program. A number of such adaptive programs are known to accompany aging and are thought to have decreased energy requirements for ancestral hunter-gatherers in their 30s, 40s and 50s. Foraging ability in modern hunter-gatherers declines rapidly, more than a decade before the average terminal age of 55 years. Given this, the human brain would have been a tremendous metabolic liability that must have been advantageously tempered by the early cellular and molecular changes of AD which begin to accumulate in all humans during early adulthood. Before the recent lengthening of life span, individuals in the ancestral environment died well before this metabolism reduction program resulted in clinical AD, thus there was never any selective pressure to keep adaptive changes from progressing to a maladaptive extent. Aging foragers may not have needed the same cognitive capacities as their younger counterparts because of the benefits of accumulated learning and life experience. It is known that during both childhood and adulthood metabolic rate in the brain decreases linearly with age. This trend is thought to reflect the fact that children have more to learn. AD "pathology" may be a natural continuation of this trend. It is characterized by decreasing cerebral metabolism, selective elimination of synapses and reliance on accumulating knowledge (especially implicit and procedural over raw brain power (working memory. Over decades of subsistence, the behaviors of aging foragers became routinized, their motor movements automated and their expertise ingrained to a point where they no longer necessitated the first-rate working memory they possessed when younger and learning actively. Alzheimer

  7. 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

  8. Metabolic-dopaminergic mapping of the 6-hydroxydopamine rat model for Parkinson's disease

    International Nuclear Information System (INIS)

    Casteels, Cindy; Lauwers, Erwin; Baekelandt, Veerle; Bormans, Guy; Laere, Koen van

    2008-01-01

    The unilateral 6-hydroxydopamine (6-OHDA) lesion rat model is a well-known acute model for Parkinson's disease (PD). Its validity has been supported by invasive histology, behavioral studies and electrophysiology. Here, we have characterized this model in vivo by multitracer imaging [glucose metabolism and dopamine transporter (DAT)] in relation to behavioral and histological parameters. Eighteen female adult Wistar rats (eight 6-OHDA-lesioned, ten controls) were investigated using multitracer [ 18 F]-fluoro-2-deoxy-D-glucose (FDG) and [ 18 F]-FECT 2'-[ 18 F]-fluoroethyl-(1R-2-exo-3-exe)-8-methyl-3-(4-chlorophenyl)- 8-azabicyclo (3.2.1)-octane-2-carboxylate small animal positron emission tomography (PET). Relative glucose metabolism and parametric DAT binding images were anatomically standardized to Paxinos space and analyzed on a voxel-basis using SPM2, supplemented by a template-based predefined volumes-of-interest approach. Behavior was characterized by the limb-use asymmetry test; dopaminergic innervation was validated by in vitro tyrosine hydroxylase staining. In the 6-OHDA model, significant glucose hypometabolism is present in the ipsilateral sensory-motor cortex (-6.3%; p = 4 x 10 -6 ). DAT binding was severely decreased in the ipsilateral caudate-putamen, nucleus accumbens and substantia nigra (all p -9 ), as confirmed by the behavioral and histological outcomes. Correlation analysis revealed a positive relationship between the degree of DAT impairment and the change in glucose metabolism in the ipsilateral hippocampus (p = 3 x 10 -5 ), while cerebellar glucose metabolism was inversely correlated to the level of DAT impairment (p -4 ). In vivo cerebral mapping of 6-OHDA-lesioned rats using [ 18 F ]-FDG and [ 18 F ]-FECT small animal PET shows molecular-functional correspondence to the cortico-subcortical network impairments observed in PD patients. This provides a further molecular validation supporting the validity of the 6-OHDA lesion model to mimic

  9. Cost-effectiveness analysis of ultrasonography screening for nonalcoholic fatty liver disease in metabolic syndrome patients.

    Science.gov (United States)

    Phisalprapa, Pochamana; Supakankunti, Siripen; Charatcharoenwitthaya, Phunchai; Apisarnthanarak, Piyaporn; Charoensak, Aphinya; Washirasaksiri, Chaiwat; Srivanichakorn, Weerachai; Chaiyakunapruk, Nathorn

    2017-04-01

    Nonalcoholic fatty liver disease (NAFLD) can be diagnosed early by noninvasive ultrasonography; however, the cost-effectiveness of ultrasonography screening with intensive weight reduction program in metabolic syndrome patients is not clear. This study aims to estimate economic and clinical outcomes of ultrasonography in Thailand. Cost-effectiveness analysis used decision tree and Markov models to estimate lifetime costs and health benefits from societal perspective, based on a cohort of 509 metabolic syndrome patients in Thailand. Data were obtained from published literatures and Thai database. Results were reported as incremental cost-effectiveness ratios (ICERs) in 2014 US dollars (USD) per quality-adjusted life year (QALY) gained with discount rate of 3%. Sensitivity analyses were performed to assess the influence of parameter uncertainty on the results. The ICER of ultrasonography screening of 50-year-old metabolic syndrome patients with intensive weight reduction program was 958 USD/QALY gained when compared with no screening. The probability of being cost-effective was 67% using willingness-to-pay threshold in Thailand (4848 USD/QALY gained). Screening before 45 years was cost saving while screening at 45 to 64 years was cost-effective. For patients with metabolic syndromes, ultrasonography screening for NAFLD with intensive weight reduction program is a cost-effective program in Thailand. Study can be used as part of evidence-informed decision making. Findings could contribute to changes of NAFLD diagnosis practice in settings where economic evidence is used as part of decision-making process. Furthermore, study design, model structure, and input parameters could also be used for future research addressing similar questions.

  10. 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)

  11. Differences in gluten metabolism among healthy volunteers, coeliac disease patients and first-degree relatives.

    Science.gov (United States)

    Caminero, Alberto; Nistal, Esther; Herrán, Alexandra R; Pérez-Andrés, Jénifer; Ferrero, Miguel A; Vaquero Ayala, Luis; Vivas, Santiago; Ruiz de Morales, José M G; Albillos, Silvia M; Casqueiro, Francisco Javier

    2015-10-28

    Coeliac disease (CD) is an immune-mediated enteropathy resulting from exposure to gluten in genetically predisposed individuals. Gluten proteins are partially digested by human proteases generating immunogenic peptides that cause inflammation in patients carrying HLA-DQ2 and DQ8 genes. Although intestinal dysbiosis has been associated with patients with CD, bacterial metabolism of gluten has not been studied in depth thus far. The aim of this study was to analyse the metabolic activity of intestinal bacteria associated with gluten intake in healthy individuals, CD patients and first-degree relatives of CD patients. Faecal samples belonging to twenty-two untreated CD patients, twenty treated CD patients, sixteen healthy volunteers on normal diet, eleven healthy volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on normal diet and sixty-nine relatives on GFD were tested for several proteolytic activities, cultivable bacteria involved in gluten metabolism, SCFA and the amount of gluten in faeces. We detected faecal peptidasic activity against the gluten-derived peptide 33-mer. CD patients showed differences in faecal glutenasic activity (FGA), faecal tryptic activity (FTA), SCFA and faecal gluten content with respect to healthy volunteers. Alterations in specific bacterial groups metabolising gluten such as Clostridium or Lactobacillus were reported in CD patients. Relatives showed similar parameters to CD patients (SCFA) and healthy volunteers (FTA and FGA). Our data support the fact that commensal microbial activity is an important factor in the metabolism of gluten proteins and that this activity is altered in CD patients.

  12. Effect of Underlying Renal Disease on Nutritional and Metabolic Profile of Older Adults with Reduced Renal Function.

    Science.gov (United States)

    Lai, Silvia; Amabile, Maria Ida; Altieri, Silvia; Mastroluca, Daniela; Lai, Carlo; Aceto, Paola; Crudo, Massimiliano; D'Angelo, Anna Rita; Muscaritoli, Maurizio; Molfino, Alessio

    2017-01-01

    Chronic kidney disease is a common condition in the general population, particularly among older adults. Renal impairment is in turn associated with metabolic and nutritional derangements and with increased risk of cardiovascular disease. To compare the metabolic, nutritional, and cardiovascular impact of reduced kidney function between patients with and without known renal disease. We enrolled consecutive outpatients (age ≥65 years) with reduced renal function who were divided into two groups: Group A with history of renal disease and Group B with unknown renal disease. Metabolic and nutritional parameters, including involuntary body weight loss (BWL) in the previous 6 months, mineral metabolism, inflammatory indices, and left ventricular mass index (LVMI), were evaluated. A total of 76 patients were enrolled. Group A ( n  = 39, M: 24, F: 15) showed greater BWL with a significant reduction of 25-hydroxyvitamin D, transferrin, cholinesterase, albumin, and LVMI with respect to Group B ( p  < 0.01). Conversely, Group B ( n  = 37, M: 23, F: 14) showed significantly increased intact parathyroid hormone, total cholesterol, low-density lipoprotein, triglycerides, and C-reactive protein when compared to Group A ( p  < 0.05). The positive history of renal disease may negatively impact on several metabolic and nutritional parameters related to increased cardiovascular risk among older adults.

  13. Adipose Tissue, Metabolic Syndrome, and Non-Alcoholic Fatty Liver Disease – A Short Review

    Directory of Open Access Journals (Sweden)

    Panayiotis Kouis

    2014-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease globally, and it is expected to rise even further as a result of the increase in obesity and related risk factors. This short review summarises current evidence on the role of adipose tissue and insulin resistance in NAFLD and the interrelationship between NAFLD and the metabolic syndrome (MetS, considering central adiposity is a major feature of both the MetS and NAFLD, and that NAFLD has been previously described as the hepatic manifestation of the MetS. In addition, genetic studies of NAFLD with relation to adiposity and insulin resistance are reviewed, and up-to-date diagnostic and therapeutic tools are also discussed.

  14. 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.)

  15. 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.

  16. Glycogen Storage Disease Type Ia: Linkage of Glucose, Glycogen, Lactic Acid, Triglyceride, and Uric Acid Metabolism

    Science.gov (United States)

    Sever, Sakine; Weinstein, David A.; Wolfsdorf, Joseph I.; Gedik, Reyhan; Schaefer, Ernst J.

    2013-01-01

    Case Summary A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides > 5,000 mg/dl. The diagnosis of type 1A glycogen storage disease (GSD) was made by liver biopsy that showed increased glycogen and absent glucose-6-phosphatase enzyme activity. She was treated with dextrose feeding, which was replaced by frequent cornstarch feeding, with improvement of her metabolic parameters. At age 18 years she had marked hypertriglyceridemia (3,860 mg/dl) and eruptive xanthomas, and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels > 75 mg/dl and lactate levels 75 mg/dl is critical in the management of this disease. PMID:23312056

  17. Sphingosine-1-Phosphate Metabolism and Its Role in the Development of Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Tomasz Wollny

    2017-03-01

    Full Text Available Beyond their role as structural molecules, sphingolipids are involved in many important cellular processes including cell proliferation, apoptosis, inflammation, and migration. Altered sphingolipid metabolism is observed in many pathological conditions including gastrointestinal diseases. Inflammatory bowel disease (IBD represents a state of complex, unpredictable, and destructive inflammation of unknown origin within the gastrointestinal tract. The mechanisms explaining the pathophysiology of IBD involve signal transduction pathways regulating gastro-intestinal system’s immunity. Progressive intestinal tissue destruction observed in chronic inflammation may be associated with an increased risk of colon cancer. Sphingosine-1-phosphate (S1P, a sphingolipid metabolite, functions as a cofactor in inflammatory signaling and becomes a target in the treatment of IBD, which might prevent its conversion to cancer. This paper summarizes new findings indicating the impact of (S1P on IBD development and IBD-associated carcinogenesis.

  18. Cognitive impairment in Alzheimer's disease correlates with ventricular width and atrophy-corrected cortical glucose metabolism

    International Nuclear Information System (INIS)

    Slansky, I.; Herholz, K.; Pietrzyk, U.; Kessler, J.; Grond, M.; Mielke, R.; Heiss, W.D.

    1995-01-01

    We compared the correlation of PET and MRI with neuropsychological tests in 26 patients with probable Alzheimer's disease (AD). The width of the temporal horns and the third ventricle, regional metabolic rates of glucose (rCMRGlu) and the proportion of cerebrospinal fluid space in mesial temporal and temporoparietal cortical regions were measured with three-dimensionally coregistered PET and MRI in two planes perpendicular to the Sylvian fissure. Highly significant correlations between rCMRGlu and neuropsychological tests were found mainly in the temporoparietal cortex, with and without correction for atrophy. Correlations of similar magnitude were seen also between most tests and the width of the temporal horns and third ventricle. Changes in the third ventricle and mesial temporal lobe were best seen with MRI, whereas PET most clearly depicted alterations in neocortical association areas. These two aspects of the disease correlated with the severity of dementia to a similar degree. (orig.)

  19. A validated disease specific prediction equation for resting metabolic rate in underweight patients with COPD

    Directory of Open Access Journals (Sweden)

    Anita Nordenson

    2010-09-01

    Full Text Available Anita Nordenson2, Anne Marie Grönberg1,2, Lena Hulthén1, Sven Larsson2, Frode Slinde11Department of Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden; 2Department of Internal Medicine/Respiratory Medicine and Allergology, Sahlgrenska Academy at University of Gothenburg, SwedenAbstract: Malnutrition is a serious condition in chronic obstructive pulmonary disease (COPD. Successful dietary intervention calls for calculations of resting metabolic rate (RMR. One disease-specific prediction equation for RMR exists based on mainly male patients. To construct a disease-specific equation for RMR based on measurements in underweight or weight-losing women and men with COPD, RMR was measured by indirect calorimetry in 30 women and 11 men with a diagnosis of COPD and body mass index <21 kg/m2. The following variables, possibly influencing RMR were measured: length, weight, middle upper arm circumference, triceps skinfold, body composition by dual energy x-ray absorptiometry and bioelectrical impedance, lung function, and markers of inflammation. Relations between RMR and measured variables were studied using univariate analysis according to Pearson. Gender and variables that were associated with RMR with a P value <0.15 were included in a forward multiple regression analysis. The best-fit multiple regression equation included only fat-free mass (FFM: RMR (kJ/day = 1856 + 76.0 FFM (kg. To conclude, FFM is the dominating factor influencing RMR. The developed equation can be used for prediction of RMR in underweight COPD patients.Keywords: pulmonary disease, chronic obstructive, basal metabolic rate, malnutrition, body composition

  20. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations.

    Science.gov (United States)

    Milić, Sandra; Lulić, Davorka; Štimac, Davor

    2014-07-28

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m(2). However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m(2)) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.

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

    Science.gov (United States)

    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

  2. Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

    Directory of Open Access Journals (Sweden)

    Rico Rueedi

    2014-02-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome.

    Science.gov (United States)

    Dietrich, Peter; Hellerbrand, Claus

    2014-08-01

    Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of chronic liver disease worldwide. Its prevalence has increased to more than 30% of adults in developed countries and its incidence is still rising. The majority of patients with NAFLD have simple steatosis but in up to one third of patients, NAFLD progresses to its more severe form nonalcoholic steatohepatitis (NASH). NASH is characterized by liver inflammation and injury thereby determining the risk to develop liver fibrosis and cancer. NAFLD is considered the hepatic manifestation of the metabolic syndrome. However, the liver is not only a passive target but affects the pathogenesis of the metabolic syndrome and its complications. Conversely, pathophysiological changes in other organs such as in the adipose tissue, the intestinal barrier or the immune system have been identified as triggers and promoters of NAFLD progression. This article details the pathogenesis of NAFLD along with the current state of its diagnosis and treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  6. Prevalence of Vitamin D Deficiency and Its Association With Metabolic Disease in Korean Orthopedic Patients.

    Science.gov (United States)

    Kim, Ki-Tack; Kang, Kyung-Chung; Shin, Dong-Eun; Lee, Sang-Hoon; Lee, Jung-Hee; Kwon, Tae-Yoon

    2015-10-01

    Vitamin D is considered essential for bone and muscle health, and some studies have demonstrated the positive effects of vitamin D on metabolic diseases and cancer. Nevertheless, a high prevalence of vitamin D deficiency has been reported in various populations, regardless of country or race. However, no studies regarding the prevalence of vitamin D deficiency in Korean orthopedic patients currently exist. This cross-sectional study included 272 male and 937 female patients aged 50 years and older who were consecutively admitted to the authors' orthopedic department. Vitamin D (25-hydroxy vitamin D), bone turnover markers (osteocalcin, c-telopeptide), and bone mineral density were measured. The prevalence of vitamin D deficiency and its association with other factors were evaluated. Mean patient age was 67.2 ± 8.9 years, and mean level of vitamin D was 16.1 ± 9.1 ng/mL. Overall, 91.2% of patients had deficient (orthopedic patients of this region was extremely low, regardless of sex and age. Although vitamin D was not directly associated with bone mineral density, there were significant associations between vitamin D and other factors related to bone health and metabolic diseases. Copyright 2015, SLACK Incorporated.

  7. Basal metabolic rate in children with chronic kidney disease and healthy control children.

    Science.gov (United States)

    Anderson, Caroline E; Gilbert, Rodney D; Elia, Marinos

    2015-11-01

    Meeting energy requirements of children with chronic kidney disease (CKD) is paramount to optimising growth and clinical outcome, but little information on this subject has been published. In this study, we examined basal metabolic rate (BMR; a component of energy expenditure) with the aim to determine whether it is related to kidney function independently of weight, height and lean body mass (LBM). Twenty children with CKD and 20 healthy age- and gender-matched control children were studied on one occasion. BMR was measured by indirect open circuit calorimetry and predicted by the Schofield equation. Estimated glomerular filtration rate (eGFR) was related to BMR and adjusted for weight, height, age and LBM measured by skinfold thickness. The adjusted BMR of children with CKD did not differ significantly from that of healthy subjects (1296 ± 318 vs.1325 ± 178 kcal/day; p = 0.720). Percentage of predicted BMR also did not differ between the two groups (102 ± 12% vs. 99 ± 14%; p = 0.570). Within the CKD group, eGFR (mean 33.7 ± 20.5 mL/min/m(2)) was significantly related to BMR (β 0.3, r = 0.517, p = 0.019) independently of nutritional status and LBM. It seems reasonable to use estimated average requirement as the basis of energy prescriptions for children with CKD (mean CKD stage 3 disease). However, those who were sicker had significantly lower metabolic rates.

  8. 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

  9. Association of erythrocyte deformability with red blood cell distribution width in metabolic diseases and thalassemia trait.

    Science.gov (United States)

    Vayá, Amparo; Alis, Rafael; Suescún, Marta; Rivera, Leonor; Murado, Julian; Romagnoli, Marco; Solá, Eva; Hernandez-Mijares, Antonio

    2015-01-01

    Increased red blood distribution width (RDW) in anemia is related to disturbances in the cellular surface/volume ratio, usually accompanied by morphological alterations, while it has been shown in inflammatory diseases that the activity of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently it has been reported that higher RDW is related with decreased erythrocyte deformability, and that it could be related with the association of RDW and increased risk of cardiovascular diseases. In order to analyze the influence of morphological alterations and proinflammatory status on the relationship between RDW and erythrocyte deformability, we analyzed erythrocyte deformability along with RDW and other hematological and biochemical parameters in 36 α-thalassemia, 20 β-thalassemia, 20 δβ-thalassemia trait carriers, 61 metabolic syndrome patients and 76 morbidly obese patients. RDW correlated inversely with erythrocyte deformability in minor β-thalassemia (r =-0.530, p thalassemia is often accompanied by more marked cell-shaped perturbations than other thalassemia traits. This could be the reason for this negative association only in this setting. Higher anisocytosis seems to be associated with greater morphologic alterations (shape/volume), which reduce erythrocyte deformability. The proinflammatory profile in metabolic patients can be related to the positive association of RDW with erythrocyte deformability found in these patients. However, further research is needed to explain the mechanisms underlying this association.

  10. Benign Prostatic Hyperplasia, Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: Is Metaflammation the Link?

    Science.gov (United States)

    Russo, Giorgio Ivan; Cimino, Sebastiano; Castelli, Tommaso; Favilla, Vincenzo; Gacci, Mauro; Carini, Marco; Condorelli, Rosita A; La Vignera, Sandro; Calogero, Aldo E; Motta, Fabio; Puzzo, Lidia; Caltabiano, Rosario; Morgia, Giuseppe

    2016-12-01

    The prevalence of prostatic inflammation (PI) is very frequent in patients affected by benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). To investigate the relationship between prostatic inflammation (PI) and the presence of MetS and non-alcoholic fatty liver disease (NAFLD) in a cohort of patients affected by BPH/LUTS. We conducted a prospective study from January 2012 to June 2014 on 264 consecutive patients, who underwent transurethral resection of the prostate for bladder outlet obstruction. Metabolic syndrome (MetS) has been defined according to the International Diabetes Federation (IDF). Prior to surgery, each patient has been evaluated for the presence of MetS and NAFLD. All surgical specimens were investigated for the presence of an inflammatory infiltrate, according to the Irani score. The prevalence of patients affected by MetS alone was 13.8% (32/232), 13.8% (32/232) by NAFLD alone, and 42.7% (99/232) by both diseases. The rate of subjects affected by MetS + NAFLD and severe PI was significantly greater than those with only one metabolic alteration (75.8% vs. 24.2%, P prostate gland by increasing severity of inflammation. Prostate 76:1528-1535, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Modulation of hepatic lipid metabolism by olive oil and its phenols in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Priore, Paola; Cavallo, Alessandro; Gnoni, Antonio; Damiano, Fabrizio; Gnoni, Gabriele V; Siculella, Luisa

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in western countries, being considered the hepatic manifestation of metabolic syndrome. Cumulative lines of evidence suggest that olive oil, used as primary source of fat by Mediterranean populations, may play a key role in the observed health benefits on NAFLD. In this review, we summarize the state of the art of the knowledge on the protective role of both major and minor components of olive oil on lipid metabolism during NAFLD. In particular, the biochemical mechanisms responsible for the increase or decrease in hepatic lipid content are critically analyzed, taking into account that several studies have often provided different and/or conflicting results in animal models fed on olive oil-enriched diet. In addition, new findings that highlight the hypolipidemic and the antisteatotic actions of olive oil phenols are presented. As mitochondrial dysfunction plays a key role in the pathogenesis of NAFLD, the targeting of these organelles with olive oil phenols as a powerful therapeutic approach is also discussed. © 2015 International Union of Biochemistry and Molecular Biology.

  12. A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

    Directory of Open Access Journals (Sweden)

    Min Yi

    2017-12-01

    Full Text Available Human neuropeptide Y (hNPY is one of the most widely expressed neurotransmitters in the human central and peripheral nervous systems. It consists of 36 highly conserved amino acid residues, and was first isolated from the porcine hypothalamus in 1982. While it is the most recently discovered member of the pancreatic polypeptide family (which includes neuropeptide Y, gut-derived hormone peptide YY, and pancreatic polypeptide, NPY is the most abundant peptide found in the mammalian brain. In order to exert particular functions, NPY needs to bind to the NPY receptor to activate specific signaling pathways. NPY receptors belong to the class A or rhodopsin-like G-protein coupled receptor (GPCR family and signal via cell-surface receptors. By binding to GPCRs, NPY plays a crucial role in various biological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. Abnormal regulation of NPY is involved in the development of a wide range of diseases, including obesity, hypertension, atherosclerosis, epilepsy, metabolic disorders, and many cancers. Thus far, five receptors have been cloned from mammals (Y1, Y2, Y4, Y5, and y6, but only four of these (hY1, hY2, hY4, and hY5 are functional in humans. In this review, we summarize the structural characteristics of human NPY receptors and their role in metabolic diseases.

  13. 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.

  14. Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

    Science.gov (United States)

    Sever, Sakine; Weinstein, David A; Wolfsdorf, Joseph I; Gedik, Reyhan; Schaefer, Ernst J

    2012-01-01

    A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m(2). Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease. Copyright © 2012. Published by Elsevier Inc.

  15. Serum uric acid, the metabolic syndrome, and the risk of chronic kidney disease in patients with type 2 diabetes.

    Science.gov (United States)

    Sheikhbahaei, Sara; Fotouhi, Akbar; Hafezi-Nejad, Nima; Nakhjavani, Manouchehr; Esteghamati, Alireza

    2014-03-01

    Serum uric acid (SUA) has been suggested as a potentially modifiable mediator associated with the metabolic syndrome. Hyperuricemia and metabolic syndrome were both associated with adverse renal outcome. However, epidemiologic data are limited regarding this relationship in patients with type 2 diabetes mellitus (T2DM). This study aims to determine whether elevated SUA is associated with an increased prevalence of metabolic risk factors, albuminuria, and chronic kidney disease (CKD) in a large sample of patients with T2DM. It also examines the combined effect of SUA and metabolic syndrome components on the odds of CKD. A total of 1463 patients with T2DM were recruited. Blood samples were obtained to measure metabolic parameters. Patients with macroalbuminuria or an estimated glomerular filtration rate of metabolic syndrome, central obesity, hypertension, high triglycerides (TGs), CKD, and macroalbuminuria was significantly higher in patients with hyperuricemia than those in the lowest tertile of SUA (T1). One standard deviation (SD) increment of SUA was significantly associated with metabolic syndrome, central obesity, and high TGs after adjustment for age, sex, estimated glomerular filtration rate (eGFR), and albuminuria. The odds of CKD went up to 1.37-fold with every 1 SD increment of SUA, independent of age, sex, and components of metabolic syndrome. There was a significant, graded increase in odds of CKD by increasing SUA levels and the number of metabolic syndrome risk factors (Pmetabolic syndrome components on the odds of CKD.

  16. Metabolic Syndrome

    Science.gov (United States)

    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 ...

  17. Tay-Sachs disease screening and counseling families at risk for metabolic disease.

    Science.gov (United States)

    Sutton, V Reid

    2002-06-01

    Carrier testing for Tay-Sachs disease should be offered to couples when at least one individual is of Ashkenazi Jewish (carrier frequency 1/30), Pennsylvania Dutch, Southern Louisiana Cajun, or Eastern Quebec French Canadian descent. Ideally, testing is done prior to conception. For Ashkenazi Jews, in whom DNA testing identifies 99.9% of carriers, DNA testing is the preferred method to ascertain carriers [14]. For non-Jewish individuals seeking carrier testing, enzyme assay should be done initially and positive or indeterminate results should be confirmed by DNA mutation analysis. If only one partner is descended from a high-risk group, that person should be tested first; only if he/ she is a carrier should the other partner be tested. If the couple is pregnant at the time carrier testing is requested, both partners should have enzyme testing (leukocyte assay for the pregnant woman and serum assay for the father) and DNA testing sent concomitantly to expedite counseling and action. Carriers are individuals with a disease causing DNA mutation or carrier range enzyme analysis results on both serum and leukocytes with no detectable mutation and no pseudodeficiency alleles. Noncarriers are individuals with normal enzyme results or carrier range enzyme results and a pseudodeficiency allele on DNA mutation analysis. If both partners are found to be carriers they should be counseled of a 25% risk of having an affected child with each pregnancy. Options to modify this risk include prenatal diagnosis by amniocentesis or chorionic villus sampling, egg or sperm donation, preimplantation diagnosis or adoption.

  18. 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 < .001, uncorrected) between 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 < .001), the lingual gyrus (z score = 4.31, P < .001), and the crus I/II of the cerebellum (z score = 3.77, P < .001), a region connected to associative cortical areas. More severe motor scores were associated with higher metabolic

  19. Diet-Gene Interactions and PUFA Metabolism: A Potential Contributor to Health Disparities and Human Diseases

    Directory of Open Access Journals (Sweden)

    Floyd H. Chilton

    2014-05-01

    Full Text Available The “modern western” diet (MWD has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6 18 carbon (C18, polyunsaturated fatty acid (PUFA linoleic acid (LA; 18:2n-6, with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS cluster that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD. Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA, CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

  20. Diet-gene interactions and PUFA metabolism: a potential contributor to health disparities and human diseases.

    Science.gov (United States)

    Chilton, Floyd H; Murphy, Robert C; Wilson, Bryan A; Sergeant, Susan; Ainsworth, Hannah; Seeds, Michael C; Mathias, Rasika A

    2014-05-21

    The "modern western" diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

  1. Diet-Gene Interactions and PUFA Metabolism: A Potential Contributor to Health Disparities and Human Diseases

    Science.gov (United States)

    Chilton, Floyd H.; Murphy, Robert C.; Wilson, Bryan A.; Sergeant, Susan; Ainsworth, Hannah; Seeds, Michael C.; Mathias, Rasika A.

    2014-01-01

    The “modern western” diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations. PMID:24853887

  2. The Western Diet-Microbiome-Host Interaction and Its Role in Metabolic Disease.

    Science.gov (United States)

    Zinöcker, Marit K; Lindseth, Inge A

    2018-03-17

    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.

  3. 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.

  4. Metabolic assessment and enteral tube feeding usage in children with acute neurological diseases.

    Science.gov (United States)

    Leite, H P; Fantozzi, G

    1998-01-01

    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. Retrospective analysis. Pediatric Intensive Care Unit of Hospital do Servidor Público Estadual de São Paulo. 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. Records of protein-energy intake, nutrient supply route, nitrogen balance and length of therapy. 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). Children with acute neurological diseases are hypercatabolic and have high urinary nitrogen losses. The initial negative nitrogen balance can be increased by more aggressive feeding regimes than the usual ones. Early tube feeding was

  5. Metabolic assessment and enteral tube feeding usage in children with acute neurological diseases

    Directory of Open Access Journals (Sweden)

    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

  6. The Relationship between Nonalcoholic Fatty Liver Disease and Colorectal Cancer: The Future Challenges and Outcomes of the Metabolic Syndrome

    OpenAIRE

    Muhidin, Said O.; Magan, Ahmed A.; Osman, Khalid A.; Syed, Shareef; Ahmed, Mohamed H.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is closely related to insulin resistance, metabolic syndrome, obesity, type 2 diabetes, and dyslipidaemia. Obesity and metabolic syndrome are associated with an increased cancer risk, and recent evidence demonstrated an association between NAFLD and colorectal cancer (CRC). The mechanism of how NAFLD can be associated with increased risk of CRC is not fully understood; however, NAFLD represents a condition of profound insulin resistance and a proinflam...

  7. Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD

    Science.gov (United States)

    Hu, Yang; Yu, Shu-Yang; Zuo, Li-Jun; Piao, Ying-Shan; Cao, Chen-Jie; Wang, Fang; Chen, Ze-Jie; Du, Yang; Lian, Teng-Hong; Liu, Gai-Fen; Wang, Ya-Jie; Chan, Piu; Chen, Sheng-Di; Wang, Xiao-Min; Zhang, Wei

    2015-01-01

    Objective To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). Methods Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. Results (1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. Conclusions PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation. PMID:26431210

  8. NUTRITION AND FITNESS (PART 1: OBESITY, THE METABOLIC SYNDROME, CARDIOVASCULAR DISEASE, AND CANCER

    Directory of Open Access Journals (Sweden)

    Artemis P. Simopoulos

    2005-12-01

    Full Text Available The proceedings of the Fifth International Conference on Nutrition and Fitness held in Athens, Greece, on June 91-2, 2004 are presented in the book as the first volume of the series. The objectives of the book are to review/discuss the latest information on nutrition and fitness by taking into consideration i genetic endowment, ii adaptation to the nutritional factors and the effect of various resources of energy on exercise and performance, iii the epidemiology of obesity, iv the relationship of nutrition and fitness to chronic diseases (cardiovascular diseases, syndrome X, obesity, osteoporosis, diabetes, cancer. The book also discusses the classification system of obesity in several countries and compares the diets used in several regions/countries. FEATURES A common, uniform strategy and evidence-based approach to organizing and interpreting the literature is used in all chapters. This textbook is composed of three parts with sub-sections in three of them. The topics of the parts are: i Obesity and Metabolic Syndrome, ii Coronary Heart Disease and iii Cancer. In each specific chapter, an epidemiological picture has been systematically developed from the data available in prospective, retrospective, case-control, and cross-sectional studies. The tables and figures are numerous, helpful and very useful. AUDIENCE This book is almost a compulsory reading for anyone interested in cardiovascular system, nutrition, metabolism, social and preventive medicine, clinical nutrition, diabetics, genetics, obesity, public health, sports medicine and for those wishing to run comprehensive research in this and relevant areas. The fact that the contributors are leading international researchers in this field makes this book more welcome. ASSESSMENT This book is almost a compulsory reading for anyone interested in pediatric injuries and for those wishing to run comprehensive research in this and relevant areas. The fact that the contributors are leading

  9. Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Bril, Fernando; Barb, Diana; Portillo-Sanchez, Paola; Biernacki, Diane; Lomonaco, Romina; Suman, Amitabh; Weber, Michelle H; Budd, Jeffrey T; Lupi, Maria E; Cusi, Kenneth

    2017-04-01

    The cut-off point of intrahepatic triglyceride (IHTG) content to define nonalcoholic fatty liver disease (NAFLD) by proton magnetic resonance spectroscopy ( 1 H-MRS) was established based on the 95th percentile in a group of healthy individuals (i.e., ≥5.56%). Whether this threshold correlates with metabolic and histological changes and whether a further accumulation of IHTG is associated with worsening of these parameters has not been properly assessed in a large cohort of patients. In this cross-sectional study, 352 subjects were carefully characterized with the following studies: liver 1 H-MRS; euglycemic insulin clamp with measurement of glucose turnover; oral glucose tolerance test; and a liver biopsy. Hepatic insulin sensitivity (suppression of endogenous glucose production by insulin) was affected early on after IHTG content was ∼1.5% and remained uniformly impaired (∼40%-45%), regardless of further IHTG accumulation. Skeletal muscle insulin sensitivity showed a gradual impairment at low degrees of IHTG accumulation, but remained unchanged after IHTG content reached the ∼6 ± 2% threshold. A similar pattern was observed for metabolic changes typically associated with NAFLD, such as hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C). In contrast, adipose tissue insulin sensitivity (suppression of free fatty acids by insulin) showed a continuous worsening across the spectrum of IHTG accumulation in NAFLD (r = -0.38; P liver disease (inflammation, ballooning, and fibrosis) was not associated with the amount of IHTG content. IHTG accumulation is strongly associated with adipose tissue insulin resistance (IR), supporting the current theory of lipotoxicity as a driver of IHTG accumulation. Once IHTG accumulation reaches ∼6 ± 2%, skeletal muscle IR, hypertriglyceridemia, and low HDL-C become fully established. Histological activity appears to have an early threshold and is not significantly influenced by increasing amounts of IHTG

  10. Evaluation of regional cerebral circulation and metabolism in moyamoya disease using positron emission computed tomography

    International Nuclear Information System (INIS)

    Kuwabara, Yasuo

    1986-01-01

    Regional cerebral blood flow, oxygen extraction fraction, metabolic rate of oxygen, blood volume and transit time were evaluated in 11 patients with moyamoya disease and 3 with suspected moyamoya disease using positron emission computed tomography. Eight of them were examined before and after EC-IC bypass surgery. Moyamoya patients were classified into four groups, namely, pediatric bilateral chronic type (over 5 years from onset), pediatric bilateral early type (within 5 years from onset), pediatric unilateral early type and adult type, according to age, duration of disease from onset and angiographic findings. These four groups showed different patterns on PET images; diffusely decreased CBF and CMRO2 in pediatric bilateral chronic type, decreased CBF and increased OEF in the frontal or temporoparietal region in pediatric bilateral early type, diffusely decreased CBF and increased OEF in the unilateral cerebral hemisphere in pediatric unilateral cerebral hemisphere in pediatric unilateral early type, and decreased CBF and CMRO2 in adult type. An increase of rCBV was demonstrated in frontal regions or basal ganglia in all groups, more prominently in pediatric patients. This was thought to be a common finding in moyamoya disease, corresponding to moyamoya vessels. Staging of moyamoya disease by PET was presented and compared to the angiographic staging. They were significantly correlated, and the stage 3 on PET image with decreased CMRO2 corresponded to the stage 3 or 4 on angiography, the most active stage of moyamoya disease. PET revealed increased CBF in the cortical area around EC-IC bypass but no remarkable changes in mean values of rCBF, OEF, CMRO2 and CBV in cerebral hemisphere. Some patients showed decreased rCBV in the basal ganglia. (J.P.N.)

  11. Relationship between Metabolic Syndrome Components and Periodontal Disease in a Japanese General Population: the Suita Study.

    Science.gov (United States)

    Kikui, Miki; Kokubo, Yoshihiro; Ono, Takahiro; Kida, Momoyo; Kosaka, Takayuki; Yamamoto, Masaaki; Watanabe, Makoto; Maeda, Yoshinobu; Miyamoto, Yoshihiro

    2017-05-01

    A positive association between metabolic syndrome (MetS) and periodontal status has recently been noted. However, no study has evaluated the relationship by sex and in a general urban population using the uniform definition proposed in the 2009 Joint Interim Statement. The aim of this study was to clarify the relationship between MetS and periodontal status using the uniform definition in a general urban Japanese population. A total of 1,856 Japanese men and women (mean age: 66.4 years) were studied using data from the Suita study. Periodontal status was evaluated by the Community Periodontal Index (CPI). MetS was defined using the 2009 Joint Interim Statement. The associations of the MetS and its components with periodontal disease were investigated using multiple logistic regression analysis adjusting for age, drinking, and smoking. Among the components of the MetS, low HDL cholesterol level was significantly associated with periodontal disease in men and women [odds ratios (OR)=2.39 and 1.53; 95% confidence intervals=1.36-4.19 and 1.06-2.19]. Furthermore, the risk of periodontal disease showed 1.43-, 1.42-, and 1.89-fold increases in those with 2, 3, and ≥4 components, respectively, compared with those having no components (P trend <0.001). For the analysis by sex, the risk of periodontal disease was increased 2.27- and 1.76-fold in those with ≥4 components in men and women, respectively (both P trend =0.001). These findings suggest that MetS and lower HDL cholesterol are associated with periodontal disease. Subjects with two or more MetS components had a significantly higher prevalence of periodontal disease.

  12. APP overexpression in the absence of NPC1 exacerbates metabolism of amyloidogenic proteins of Alzheimer's disease

    Science.gov (United States)

    Maulik, Mahua; Peake, Kyle; Chung, JiYun; Wang, Yanlin; Vance, Jean E.; Kar, Satyabrata

    2015-01-01

    Amyloid-β (Aβ) peptides originating from β-amyloid precursor protein (APP) are critical in Alzheimer's disease (AD). Cellular cholesterol levels/distribution can regulate production and clearance of Aβ peptides, albeit with contradictory outcomes. To better understand the relationship between cholesterol homeostasis and APP/Aβ metabolism, we have recently generated a bigenic ANPC mouse line overexpressing mutant human APP in the absence of Niemann-Pick type C-1 protein required for intracellular cholesterol transport. Using this unique bigenic ANPC mice and complementary stable N2a cells, we have examined the functional consequences of cellular cholesterol sequestration in the endosomal–lysosomal system, a major site of Aβ production, on APP/Aβ metabolism and its relation to neuronal viability. Levels of APP C-terminal fragments (α-CTF/β-CTF) and Aβ peptides, but not APP mRNA/protein or soluble APPα/APPβ, were increased in ANPC mouse brains and N2a-ANPC cells. These changes were accompanied by reduced clearance of peptides and an increased level/activity of γ-secretase, suggesting that accumulation of APP-CTFs is due to decreased turnover, whereas increased Aβ levels may result from a combination of increased production and decreased turnover. APP-CTFs and Aβ peptides were localized primarily in early-/late-endosomes and to some extent in lysosomes/autophagosomes. Cholesterol sequestration impaired endocytic-autophagic-lysosomal, but not proteasomal, clearance of APP-CTFs/Aβ peptides. Moreover, markers of oxidative stress were increased in vulnerable brain regions of ANPC mice and enhanced β-CTF/Aβ levels increased susceptibility of N2a-ANPC cells to H2O2-induced toxicity. Collectively, our results show that cellular cholesterol sequestration plays a key role in APP/Aβ metabolism and increasing neuronal vulnerability to oxidative stress in AD-related pathology. PMID:26433932

  13. Inflammation markers are associated with metabolic syndrome and ventricular arrhythmia in patients with coronary artery disease

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    Krzysztof Safranow

    2016-02-01

    Full Text Available Background: Inflammation plays a major role in the development and progression of atherosclerosis and coronary artery disease (CAD. Inflammation markers, including white blood cell (WBC count, C-reactive protein (CRP and interleukin-6 (IL-6, are widely used for cardiovascular risk prediction. The aim of the study was to establish factors associated with WBC, CRP and IL-6 in patients with CAD. Two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism were analyzed (C34T AMPD1, G22A ADA. Methods: Plasma concentrations of IL-6 were measured using high-sensitivity ELISA kits, and the nephelometric method was used for high-sensitivity CRP (hs-CRP measurement in 167 CAD patients. Results: Presence of metabolic syndrome (MS and its components, presence of heart failure, severity of CAD symptoms, severe past ventricular arrhythmia (sustained ventricular tachycardia [sVT] or ventricular fibrillation [VF], lower left ventricle ejection fraction, higher left ventricle mass index, higher end-diastolic volume and higher number of smoking pack-years were significantly associated with higher WBC, CRP and IL-6. Strong associations with arrhythmia were observed for IL-6 (median 3.90 vs 1.89 pg/mL, p<0.00001 and CRP concentration (6.32 vs 1.47 mg/L, p=0.00009, while MS was associated most strongly with IL-6. CRP and IL-6 were independent markers discriminating patients with sVT or VF. There were no associations between AMPD1 or ADA genotypes and inflammation markers. Conclusions: WBC, CRP and IL-6 are strongly associated with components of the metabolic syndrome. Their strong association with life-threatening ventricular arrhythmia emphasizes the proarrhythmic role of inflammation in the increased cardiovascular risk of CAD patients.

  14. Thiamin diphosphate-dependent enzymes: from enzymology to metabolic regulation, drug design and disease models.

    Science.gov (United States)

    Bunik, Victoria I; Tylicki, Adam; Lukashev, Nikolay V

    2013-12-01

    Bringing a knowledge of enzymology into research in vivo and in situ is of great importance in understanding systems biology and metabolic regulation. The central metabolic significance of thiamin (vitamin B1 ) and its diphosphorylated derivative (thiamin diphosphate; ThDP), and the fundamental differences in the ThDP-dependent enzymes of metabolic networks in mammals versus plants, fungi and bacteria, or in health versus disease, suggest that these enzymes are promising targets for biotechnological and medical applications. Here, the in vivo action of known regulators of ThDP-dependent enzymes, such as synthetic structural analogs of the enzyme substrates and thiamin, is analyzed in light of the enzymological data accumulated during half a century of research. Mimicking the enzyme-specific catalytic intermediates, the phosphonate analogs of 2-oxo acids selectively inhibit particular ThDP-dependent enzymes. Because of their selectivity, use of these compounds in cellular and animal models of ThDP-dependent enzyme malfunctions improves the validity of the model and its predictive power when compared with the nonselective and enzymatically less characterized oxythiamin and pyrithiamin. In vitro studies of the interaction of thiamin analogs and their biological derivatives with potential in vivo targets are necessary to identify and attenuate the analog selectivity. For both the substrate and thiamin synthetic analogs, in vitro reactivities with potential targets are highly relevant in vivo. However, effective concentrations in vivo are often higher than in vitro studies would suggest. The significance of specific inihibition of the ThDP-dependent enzymes for the development of herbicides, antibiotics, anticancer and neuroprotective strategies is discussed. © 2013 FEBS.

  15. Physical Fitness and Metabolic Syndrome in Children with Repaired Congenital Heart Disease Compared with Healthy Children.

    Science.gov (United States)

    Zaqout, Mahmoud; Vandekerckhove, Kristof; Michels, Nathalie; Bove, Thierry; François, Katrien; De Wolf, Daniel

    2017-12-01

    To determine whether children who underwent surgery for congenital heart disease (CHD) are as fit as their peers. We studied 66 children (6-14 years) who underwent surgery for ventricular septal defect (n = 19), coarctation of aorta (n = 10), tetralogy of Fallot (n = 15), and transposition of great arteries (n = 22); and 520 healthy children (6-12 years). All children performed physical fitness tests: cardiorespiratory fitness, muscular strength, balance, flexibility, and speed. Metabolic score was assessed through z-score standardization using 4 components: waist circumference, blood pressure, blood lipids, and insulin resistance. Assessment also included self-reported and accelerometer-measured physical activity. Linear regression analyses with group (CHD vs control) as a predictor were adjusted for age, body mass index, physical activity, and parental education. Measured physical activity level, body mass index, cardiorespiratory fitness, flexibility, and total metabolic score did not differ between children with CHD and controls, whereas reported physical activity was greater in the CHD group than control group. Boys with CHD were less strong in upper muscular strength, speed, and balance, whereas girls with CHD were better in lower muscular strength and worse in balance. High-density lipoprotein was greater in boys and girls with CHD, whereas boys with CHD showed unhealthier glucose homeostasis. Appropriate physical fitness was achieved in children after surgery for CHD, especially in girls. Consequently, children with CHD were not at increased total metabolic risk. Lifestyle counseling should be part of every patient interaction. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Impaired homocysteine metabolism in patients with alcoholic liver disease in Taiwan.

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    Chien, Yi-Wen; Chen, Ya-Ling; Peng, Hsiang-Chi; Hu, Jui-Ting; Yang, Sien-Sing; Yang, Suh-Ching

    2016-08-01

    ​Impaired homocysteine metabolism plays an important role in alcoholic liver disease (ALD); however, there are limited data about its relationship with the risk and severity of patients with ALD in Taiwan. To understand plasma homocysteine and related vitamin concentrations in patients with ALD in Taiwan, we recruited 50 male patients with ALD from Cathay General Hospital, with 49 age-and gender-matched healthy adults as the control group. The Institutional Review Board for Human Studies approved the study, and informed consent was obtained from all patients prior to blood collection. Significantly higher plasma homocysteine concentrations but lower folate concentrations were obtained from patients with ALD. In addition, patients with ALD showed a significant lower erythrocyte reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio but higher plasma thiobarbituric acid-reactive substance (TBARS) concentration, which indicated that oxidative stress was occurring in patients with ALD. A negative correlation between plasma folate and homocysteine was observed in all subjects. There was also a negative correlation between plasma homocysteine and the erythrocyte GSH/GSSG ratio which indicated impaired homocysteine metabolism may have disrupted the antioxidative status. In addition, patients in Child-Pugh Class B and C showed higher plasma vitamin B12 concentrations than did patients without cirrhosis and patients in Child-Pugh Class A. These findings show that impaired homocysteine metabolism was observed in patients with ALD in Taiwan. In addition, the plasma vitamin B12 concentration may reflect the degree of liver injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Considerations on pig models for appetite, metabolic syndrome and obese type 2 diabetes: Form food intake to metabolic disease

    NARCIS (Netherlands)

    Koopmans, S.J.; Schuurman, T.

    2015-01-01

    (Mini)pigs have proven to be a valuable animal model in nutritional, metabolic and cardiovascular research and in some other biomedical research areas (toxicology, neurobiology). The large resemblance of (neuro)anatomy, the gastro-intestinal tract, body size, body composition, and the omnivorous

  18. Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson's disease

    International Nuclear Information System (INIS)

    Berti, Valentina; Polito, Cristina; Vanzi, Eleonora; Cristofaro, Maria Teresa de; Pellicano, Giannantonio; Mungai, Francesco; Formiconi, Andreas Robert; Pupi, Alberto; Ramat, Silvia; Marini, Paolo; Sorbi, Sandro

    2010-01-01

    The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients. Twenty-six de novo untreated PD patients were scanned with 123 I-FP-CIT SPECT and 18 F-FDG PET. The dopaminergic impairment was measured with putaminal 123 I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP OSEM ) and the least-squares (LS) method (BP LS ). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc. The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP OSEM and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP LS and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p LS is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects. (orig.)

  19. Hepcidin and iron metabolism disorders in patients with chronic kidney disease

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    Jelić Marija

    2013-01-01

    Full Text Available Bacground/Aim. Hepcidin may play a pathogenetic role in iron metobolism disorders. The aim of this study was to determine the correlation between hepcidin concentration and parameters of iron metabolism in patients with different stage of chronic kidney disease (CKD. Methods. The study involved 104 patients with CKD: 64 on hemodialysis (HD and 40 patients in pre-dialysis stadium (pre-HD with adequate erythropoetin therapy and iron supplementation. The HD group was divided in four subgroups according to the level of serum ferritin (up to 100; 100-199; 200-499 and over 500 ng/mL. Parameters of anemia, iron status, inflamation and hepcidin level were evaluated. Results. The HD patients had a significantly lower eritrocyte count, erythrocytes indexes, hemoglobin and transferrin saturation and significantly higher iron, ferritin, hepcidin and total iron binding capacity (TIBC. The HD subgroups up to 199 ng/mL of serum feritin had lower high-sensitivity Creactive protein (hsCRP, iron and higher unbuffered iron binding capacity (UIBC, transferrin saturation and TIBC compared to the HD subgroups over 200 ng/mL. The lowest and the highest ferritin subgroups had the highest hepcidin level and it showed significant correlation with ferritin. Conclusion. Hepcidin may serve as a marker for better diagnosing and monitoring anemia and iron metabolism disorders in CKD.

  20. 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=

  1. Deficiency in the Heat Stress Response Could Underlie Susceptibility to Metabolic Disease.

    Science.gov (United States)

    Rogers, Robert S; Morris, E Matthew; Wheatley, Joshua L; Archer, Ashley E; McCoin, Colin S; White, Kathleen S; Wilson, David R; Meers, Grace M E; Koch, Lauren G; Britton, Steven L; Thyfault, John P; Geiger, Paige C

    2016-11-01

    Heat treatment (HT) effectively prevents insulin resistance and glucose intolerance in rats fed a high-fat diet (HFD). The positive metabolic actions of heat shock protein 72 (HSP72), which include increased oxidative capacity and enhanced mitochondrial function, underlie the protective effects of HT. The purpose of this study was to test the ability of HSP72 induction to mitigate the effects of consumption of a short-term 3-day HFD in rats selectively bred to be low-capacity runners (LCRs) and high-capacity runners (HCRs)-selective breeding that results in disparate differences in intrinsic aerobic capacity. HCR and LCR rats were fed a chow or HFD for 3 days and received a single in vivo HT (41°C, for 20 min) or sham treatment (ST). Blood, skeletal muscles, liver, and adipose tissues were harvested 24 h after HT/ST. HT decreased blood glucose levels, adipocyte size, and triglyceride accumulation in liver and muscle and restored insulin sensitivity in glycolytic muscles from LCR rats. As expected, HCR rats were protected from the HFD. Importantly, HSP72 induction was decreased in LCR rats after only 3 days of eating the HFD. Deficiency in the highly conserved stress response mediated by HSPs could underlie susceptibility to metabolic disease with low aerobic capacity. © 2016 by the American Diabetes Association.

  2. Impact of metabolic syndrome on resting energy expenditure in patients with chronic kidney disease.

    Science.gov (United States)

    Rodrigues, Carolina Q D; Santos, Jacqueline A P; Quinto, Beata M R; Marrocos, Mauro S M; Teixeira, Andrei A; Rodrigues, Cássio J O; Batista, Marcelo C

    2016-10-01

    Resting energy expenditure (REE) changes in patients with chronic kidney disease (CKD) may contribute to mortality increase. The obesity and inflammation is associated with high REE and when not compensated by adequate intake, may determine an unfavorable clinical outcome in this population. We aimed to evaluate the influence of metabolic syndrome (MetS) on REE in CKD patients. One hundred eighty-three patients were stratified according to glomerular filtration rate (GFR) and divided in groups: without CKD (GFR > 60 ml/min/1.73 m 2 ) and CKD (GFR Patients without MetS, REE correlated with estimated GFR and the protein equivalent (r = 0.33, P patients, these correlations were not observed. The presence of CKD is independently associated with reduced REE. The observed decrease in REE is reversed in patients with MetS independent of renal function. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  3. Neutral lipid storage disease with myopathy: A whole-body nuclear MRI and metabolic study

    International Nuclear Information System (INIS)

    Laforet, Pascal; Stojkovic, Tanya; Wahbi, Karim; Eymard, Bruno; Bassez, Guillaume; Carlier, Pierre G.; Clement, Karine; Petit, Francois M.; Carlier, Robert-Yves

    2013-01-01

    Neutral lipid storage disease with myopathy (NLSDM) is caused by a mutation in the gene encoding adipose triglyceride lipase (ATGL), and is characterized by the presence of numerous triglyceride-containing cytoplasmic droplets in type I muscle fibers. Major clinical manifestations concern the heart and skeletal muscle, and some patients also present diabetes mellitus. We report the clinical, metabolic, and whole-body nuclear magnetic resonance imaging findings of three patients with NLSDM. Muscle MRI study was consistent with previous descriptions, and allowed to show a common pattern of fatty replacement. Muscle changes predominated in the paravertebral muscles, both compartments of legs, and posterior compartment of the thighs. A more variable distribution of muscle involvement was observed on upper limbs, with marked asymmetry in one patient, and alterations predominating on supra and infra spinatus, biceps brachialis and anterior compartment of arms. Cardiac NMR studies revealed anomalies despite normal echocardiography in two patients. Endocrine studies showed low leptin and adiponectine levels, a moderate increase in insulin levels at fasting state, and even greater increase after oral glucose tolerance test in one patient. Two patients had elevated triglycerides and low cholesterol-HDL. Based on these analyses, regular control of cardio-metabolic risks appear mandatory in the clinical follow-up of these subjects. (authors)

  4. [Chronic obstructive pulmonary disease concurrent with metabolic syndrome: Pathophysiological and clinical features].

    Science.gov (United States)

    Budnevsky, A V; Ovsyannikov, E S; Labzhania, N B

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) still remains a serious public health problem, which is a common cause of disability and death in the able-bodied population. Furthermore, the number of patients with metabolic syndrome (MS) is steadily increasing worldwide. Recently, there is also an increase in the number of patients with COPD concurrent with MS, which is a mutually confounding risk factor for concomitant cardiovascular disease and adversely affects prognosis in these patients. Systemic subclinical inflammation is a common link between COPD and the components of MS. Systemic inflammation in patients with comorbidity is complemented by an inflammatory process in the abdominal visceral adipose tissue that serves as a source of proinflammatory adipokines (leptin, resistin, and tumor necrosis factor-α). Patients with COPD in the presence of MS components have in general higher ventilation needs, more obvious clinical manifestations of bronchopulmonary diseases, and more frequent COPD exacerbations and frequently require higher doses of inhaled glucocorticosteroids. As compared with normal-weight patients with COPD, obese patients with this condition have more limited physical activity and much more exercise intolerance. There are currently no practical recommendations for the management of patients with comorbidity; patients with COPD concurrent with MS need an individual therapeutic approach. It is important to elaborate a package of preventive measures to improve quality of life in patients, to reduce the incidence of systemic complications, and to achieve symptomatic improvements. Thus, to develop and implement practical guidelines for physicians and patients are an urgent issue.

  5. Measurement of lumbar spine bone mineral content using dual photon absorptiometry. Usefulness in metabolic bone diseases

    International Nuclear Information System (INIS)

    Delmas, P.D.; Duboeuf, F.; Braillon, P.; Meunier, P.J.

    1988-01-01

    Measurement of bone density using an accurate, non-invasive method is a crucial step in the clinical investigation of metabolic bone diseases, especially osteoporosis. Among the recently available techniques, measurement of lumbar spine bone mineral content (BMC) using dual photon absorptiometry appears as the primary method because it is simple, inexpensive, and involves low levels of radiation exposure. In this study, we measured the BMC in 168 normal adults and 95 patients. Results confirmed the good reproducibility and sensitivity of this technique for quantifying bone loss in males and females with osteoporosis. Significant bone loss was found in most females with primary hyperparathyroidism. Dual photon absorptiometry can also be used for quantifying increases in bone mass in Paget disease of bone and diffuse osteosclerosis. Osteomalacia is responsible for a dramatic fall in BMC reflecting lack of mineralization of a significant portion of the bone matrix, a characteristic feature in this disease. Furthermore, in addition to being useful for diagnostic purposes and for evaluation of the vertebral fracture risk, lumbar spine absorptiometry can be used for monitoring the effectiveness of bone-specific treatments [fr

  6. The Role of Interleukin-18, Oxidative Stress and Metabolic Syndrome in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Johanna O. Ojala

    2017-05-01

    Full Text Available The role of interleukins (ILs and oxidative stress (OS in precipitating neurodegenerative diseases including sporadic Alzheimer’s disease (AD, requires further clarification. In addition to neuropathological hallmarks—extracellular neuritic amyloid-β (Aβ plaques, neurofibrillary tangles (NFT containing hyperphosphorylated tau and neuronal loss—chronic inflammation, as well as oxidative and excitotoxic damage, are present in the AD brain. The pathological sequelae and the interaction of these events during the course of AD need further investigation. The brain is particularly sensitive to OS, due to the richness of its peroxidation-sensitive fatty acids, coupled with its high oxygen demand. At the same time, the brain lack robust antioxidant systems. Among the multiple mechanisms and triggers by which OS can accumulate, inflammatory cytokines can sustain oxidative and nitrosative stress, leading eventually to cellular damage. Understanding the consequences of inflammation and OS may clarify the initial events underlying AD, including in interaction with genetic factors. Inflammatory cytokines are potential inducers of aberrant gene expression through transcription factors. Susceptibility disorders for AD, including obesity, type-2 diabetes, cardiovascular diseases and metabolic syndrome have been linked to increases in the proinflammatory cytokine, IL-18, which also regulates multiple AD related proteins. The association of IL-18 with AD and AD-linked medical conditions are reviewed in the article. Such data indicates that an active lifestyle, coupled to a healthy diet can ameliorate inflammation and reduce the risk of sporadic AD.

  7. The Role of Interleukin-18, Oxidative Stress and Metabolic Syndrome in Alzheimer's Disease.

    Science.gov (United States)

    Ojala, Johanna O; Sutinen, Elina M

    2017-05-21

    The role of interleukins (ILs) and oxidative stress (OS) in precipitating neurodegenerative diseases including sporadic Alzheimer's disease (AD), requires further clarification. In addition to neuropathological hallmarks-extracellular neuritic amyloid-β (Aβ) plaques, neurofibrillary tangles (NFT) containing hyperphosphorylated tau and neuronal loss-chronic inflammation, as well as oxidative and excitotoxic damage, are present in the AD brain. The pathological sequelae and the interaction of these events during the course of AD need further investigation. The brain is particularly sensitive to OS, due to the richness of its peroxidation-sensitive fatty acids, coupled with its high oxygen demand. At the same time, the brain lack robust antioxidant systems. Among the multiple mechanisms and triggers by which OS can accumulate, inflammatory cytokines can sustain oxidative and nitrosative stress, leading eventually to cellular damage. Understanding the consequences of inflammation and OS may clarify the initial events underlying AD, including in interaction with genetic factors. Inflammatory cytokines are potential inducers of aberrant gene expression through transcription factors. Susceptibility disorders for AD, including obesity, type-2 diabetes, cardiovascular diseases and metabolic syndrome have been linked to increases in the proinflammatory cytokine, IL-18, which also regulates multiple AD related proteins. The association of IL-18 with AD and AD-linked medical conditions are reviewed in the article. Such data indicates that an active lifestyle, coupled to a healthy diet can ameliorate inflammation and reduce the risk of sporadic AD.

  8. PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome.

    Science.gov (United States)

    Jurkowski, W; Roomp, K; Crespo, I; Schneider, J G; Del Sol, A

    2011-08-11

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The difference in gene expression seen when comparing wild-type phosphorylated with mutant non-phosphorylated PPARγ may have important consequences for the cellular molecular network, the state of which can be shifted from the healthy to a stable diseased state. We found that a group of differentially expressed genes are involved in bi-stable switches and form a core network, the state of which changes with disease progression. These findings support the idea that bi-stable switches may be a mechanism for locking the core gene network into a diseased state and for efficiently propagating perturbations to more distant regions of the network. A structural analysis of the PPARγ-RXRα dimer complex supports the hypothesis of a major structural change between the two states, and this may represent an important mechanism leading to the differential expression observed in the core network.

  9. MAGNESIUM METABOLISM AND CLINICAL CHARACTERISTICS OF PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    A. V. Yezhov

    2010-01-01

    Full Text Available Aim. To study relationship of the clinical state and cardiac functional parameters with magnesium metabolism indices in patients with chronic ischemic heart disease (IHD.Material and methods. Patients with stable angina pectoris, II-III class (n=480 were involved into the study. Evaluation of the following items was performed: disease course, anxiodepressive syndrome intensity, exercise tolerance, blood and urine electrolyte profile, systolic and diastolic left ventricle function, endothelium-dependent and endotheliumnondependent vasodilatation, i/v magnesium load test, Holter electrocardiogram monitoring.Results. High prevalence of systemic magnesium deficiency (17.9 and 37.5% according to serum and erythrocyte levels, respectively was found in IHD patients. Severity of magnesium deficiency in IHD patients depended on duration of disease, experience of myocardial infarction, myocardial ischemia seriousness, disorders of endothelium vasodilating function and left ventricle diastolic function, severity of concomitant anxiety. Exercise tests were changed in IHD patients with magnesium deficiency.Conclusion. The study data let to consider that magnesium deficiency involves into the IHD pathogenesis.

  10. The Role of Lipid and Lipoprotein Metabolism in Non‐Alcoholic Fatty Liver Disease

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    Francesco Massimo Perla

    2017-06-01

    Full Text Available Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a “multiple-hit process” where the first “hit” is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity. At the onset of disease, NAFLD is characterized by hepatic triglyceride accumulation and insulin resistance. Liver fat accumulation is associated with increased lipotoxicity from high levels of free fatty acids, free cholesterol and other lipid metabolites. As a consequence, mitochondrial dysfunction with oxidative stress and production of reactive oxygen species and endoplasmic reticulum stress-associated mechanisms, are activated. The present review focuses on the relationship between intra-cellular lipid accumulation and insulin resistance, as well as on lipid and lipoprotein metabolism in NAFLD.

  11. Are adipocytokines inflammatory or metabolic mediators in patients with inflammatory bowel disease?

    Directory of Open Access Journals (Sweden)

    Kahraman R

    2017-09-01

    Full Text Available Resul Kahraman,1 Turan Calhan,1 Abdurrahman Sahin,1 Kamil Ozdil,1 Zuhal Caliskan,1 Elif Sinem Bireller,2 Bedia Cakmakoglu3 1Department of Gastroenterology, Umraniye Education and Training Hospital, Health Sciences University, 2Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul Yeni Yuzyil University, 3Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey Abstract: This study examined the adiponectin and leptin levels and insulin resistance (IR in patients with inflammatory bowel disease (IBD and the associations between these factors and IBD characteristics. Fasting serum leptin, adiponectin, glucose, and insulin levels, as well as inflammatory parameters, were measured in 105 patients with IBD (49 patients with Crohn’s disease [CD], 56 patients with ulcerative colitis [UC] and 98 healthy controls [HC]. IR was evaluated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR. Disease activity and severity in patients with UC were evaluated using the Truelove–Witts index, and patients with CD were evaluated using the Crohn’s Disease Activity Index. Serum adiponectin levels were found to be significantly lower in patients with CD and UC (p<0.001. Serum leptin levels were also found to be significantly higher in both the UC and CD groups (p<0.001. When HOMA-IR levels were compared, no significant difference was detected for either the CD or UC groups compared with the controls. In conclusion, it was shown that leptin levels increased and adiponectin levels decreased in patients with IBD, which is thought to be related to chronic inflammation. The effects of adipocytokines in patients with IBD with inflammatory and metabolic processes need to be investigated in further broader studies. Keywords: ulcerative colitis, Crohn’s disease, insulin resistance, adiponectin, leptin

  12. 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

  13. Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Croci, Ilaria; Byrne, Nuala M; Choquette, Stéphane; Hills, Andrew P; Chachay, Veronique S; Clouston, Andrew D; O'Moore-Sullivan, Trisha M; Macdonald, Graeme A; Prins, Johannes B; Hickman, Ingrid J

    2013-11-01

    In non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is intricately linked with a number of metabolic alterations. We studied substrate utilisation in NAFLD during basal, insulin-stimulated and exercise conditions, and correlated these outcomes with disease severity. 20 patients with NAFLD (mean ± SD body mass index (BMI) 34.1 ± 6.7 kg/m(2)) and 15 healthy controls (BMI 23.4 ± 2.7 kg/m(2)) were assessed. Respiratory quotient (RQ), whole-body fat (Fat ox) and carbohydrate (CHO ox) oxidation rates were determined by indirect calorimetry in three conditions: basal (resting and fasted), insulin-stimulated (hyperinsulinaemic-euglycaemic clamp) and exercise (cycling at an intensity to elicit maximal Fat ox). Severity of disease and steatosis were determined by liver histology, hepatic Fat ox from plasma β-hydroxybutyrate concentrations, aerobic fitness expressed as VO2 peak, and visceral adipose tissue (VAT) measured by computed tomography. Within the overweight/obese NAFLD cohort, basal RQ correlated positively with steatosis (r=0.57, p=0.01) and was higher (indicating smaller contribution of Fat ox to energy expenditure) in patients with NAFLD activity score (NAS) ≥ 5 vs hepatic Fat ox (ie, β-hydroxybutyrate, p=0.004). During exercise, they achieved lower maximal Fat ox (2.5 ± 1.4 vs. 5.8 ± 3.7 mg/kg FFM/min, p=0.002) and lower VO2 peak (phepatic Fat ox and reduced whole-body Fat ox under basal and exercise conditions. There was an inverse relationship between ability to oxidise fat in basal conditions and histological features of NAFLD including severity of steatosis and NAS.

  14. The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases

    Directory of Open Access Journals (Sweden)

    Youngkyun Lee

    2013-10-01

    Full Text Available The balance between osteoblast-dependent bone formationand osteoclast-dependent bone resorption maintains bonehomeostasis. In inflammatory conditions, this balance shiftstoward bone resorption, causing osteolytic bone lesionsobserved in rheumatoid arthritis and periodontitis. A recentlydiscovered family of cytokine IL-17 is widely reported tomediate diverse inflammatory processes. During the lastdecade, novel roles for IL-17 in skeletal homeostasis have beendiscovered indicating the potential importance of this cytokinein bone metabolism. This review will summarize and discussthe involvement of IL-17 during bone homeostasis in bothphysiologic and pathologic conditions. A better understandingof the role of IL-17 in skeletal systems warrants an advance inbone biology, as well as development of therapeutic strategiesagainst bone-lytic diseases, such as rheumatoid arthritis andperiodontitis. [BMB Reports 2013; 46(10: 479-483

  15. Brain Metabolic Dysfunction in Capgras Delusion During Alzheimer's Disease: A Positron Emission Tomography Study.

    Science.gov (United States)

    Jedidi, H; Daury, N; Capa, R; Bahri, M A; Collette, F; Feyers, D; Bastin, C; Maquet, P; Salmon, E

    2015-11-01

    Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since little is known regarding the neural correlates of Capgras syndrome, the cerebral metabolic pattern of a patient with probable Alzheimer's disease (AD) and Capgras syndrome was compared with those of 24-healthy elderly participants and 26 patients with AD without delusional syndrome. Comparing the healthy group with the AD group, the patient with AD had significant hypometabolism in frontal and posterior midline structures. In the light of current neural models of face perception, our patients with Capgras syndrome may be related to impaired recognition of a familiar face, subserved by the posterior cingulate/precuneus cortex, and impaired reflection about personally relevant knowledge related to a face, subserved by the dorsomedial prefrontal cortex. © The Author(s) 2013.

  16. The hands in metabolic skeletal diseases 1. A method of high-detailed contact radiography

    International Nuclear Information System (INIS)

    Shotemor, Sh.Sh.; Tret'yakov, A.E.

    1982-01-01

    A method of high-detailed contact radiography of the hands consists in the the screenless x-ray on the fine grained technical film employing microfocus with consecutive optical enlargement of the appearance. Various specimens of home-made tecinical film have been tried, the best results were obtained with the PT-5 film type (an opportunity of 7-fold optical magnification without interfering effect of the emulsion granularity). The method provides for a significant diagnostic advantage, affording to reveal minimal manifestations of subperiosteal, intracortical, and enosteal bone tissue resorption, as well as tiny calcinates in soft tissues. Pathological bone disorders were discovered in 63 out of 142 examined patients, suspected of metabolic diseases of the skeleton [ru

  17. Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Susann Lehmann

    2017-02-01

    Full Text Available Familial forms of Parkinson's disease (PD caused by mutations in PINK1 are linked to mitochondrial impairment. Defective mitochondria are also found in Drosophila models of PD with pink1 mutations. The co-enzyme nicotinamide adenine dinucleotide (NAD+ is essential for both generating energy in mitochondria and nuclear DNA repair through NAD+-consuming poly(ADP-ribose polymerases (PARPs. We found alterations in NAD+ salvage metabolism in Drosophila pink1 mutants and showed that a diet supplemented with the NAD+ precursor nicotinamide rescued mitochondrial defects and protected neurons from degeneration. Additionally, a mutation of Parp improved mitochondrial function and was neuroprotective in the pink1 mutants. We conclude that enhancing the availability of NAD+ by either the use of a diet supplemented with NAD+ precursors or the inhibition of NAD+-dependent enzymes, such as PARPs, which compete with mitochondria for NAD+, is a viable approach to preventing neurotoxicity associated with mitochondrial defects.

  18. Sex Factors in the Metabolic Syndrome as a Predictor of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Sunghwan Suh

    2014-12-01

    Full Text Available BackgroundMetabolic syndrome (MetS is a condition characterized by a cluster of metabolic disorders and is associated with increased risk of cardiovascular disease (CVD. This study analyzed data from the Korean Health and Genome Study to examine the impact of MetS on CVD.MethodsA total of 8,898 subjects (4,241 males and 4,657 females, 40 to 69 years of age, were enrolled and evaluated for the development of new onset CVD from 2001 to 2012 (median 8.1 years of follow-up.ResultsThe prevalence of MetS at baseline was 22.0% (932/4,241 and 29.7% (1,383/4,657 in males and females, respectively. MetS was associated with increased risk of coronary heart disease (CHD; hazard ratio [HR], 1.818; 95% confidence interval [CI], 1.312 to 2.520 in males; HR, 1.789; 95% CI, 1.332 to 2.404 in females and CVD (HR, 1.689; 95% CI, 1.295 to 2.204 in males; HR, 1.686; 95% CI, 1.007 to 2.192 in females. Specifically, MetS was associated with risk of future stroke in females only (HR, 1.486; 95% CI, 1.007 to 2.192. Among MetS components, abdominal obesity and hypertension were independent predictors of both CHD and CVD. In addition, a higher number of MetS components correlated with higher CVD risk.ConclusionMetS is a significant risk factor for the development of CVD although its impact varies between sexes.

  19. Evidence for Bone and Mineral Metabolism Alterations in Children With Autosomal Dominant Polycystic Kidney Disease.

    Science.gov (United States)

    De Rechter, Stéphanie; Bacchetta, Justine; Godefroid, Nathalie; Dubourg, Laurence; Cochat, Pierre; Maquet, Julie; Raes, Ann; De Schepper, Jean; Vermeersch, Pieter; Van Dyck, Maria; Levtchenko, Elena; D'Haese, Patrick; Evenepoel, Pieter; Mekahli, Djalila

    2017-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Hypophosphatemia was demonstrated in adult patients with preserved renal function, together with high fibroblast growth factor 23 (FGF23) and low soluble Klotho levels. The latter explained the relative FGF23 hyporesponsiveness in this cohort. Evaluating phosphate and bone mineral metabolism in children with ADPKD compared with what is known in adult ADPKD patients. Observational cross-sectional study. Multicenter study via ambulatory care in tertiary centers. Ninety-two children with ADPKD (52 males; mean ± standard deviation age, 10.2 ± 5.0 years) and 22 healthy controls (HCs, 10 males; mean ± standard deviation age, 10.3 ± 4.1 years). The predictor was early ADPKD stage. Bone mineral metabolism and renal phosphate handling were the main outcome measures. Performed measurements were serum phosphate, tubular maximum phosphorus reabsorption per glomerular filtration rate, FGF23, soluble Klotho, sclerostin, and bone alkaline phosphatase. ADPKD children had significantly lower serum phosphate levels compared with HC. Low tubular maximum phosphorus reabsorption per glomerular filtration rate was observed in 24% of patients, although not significantly different from HC. Serum FGF23 and soluble Klotho levels were comparable between patients and HC. In addition, we showed decreased bone alkaline phosphatase levels in ADPKD children, suggesting suppressed bone formation. This report demonstrates hypophosphatemia and suppressed bone formation in a pediatric ADPKD cohort, with preserved renal function, compared with HC. Although FGF23 levels were not different from controls, they should be considered inappropriate, given the concomitant hypophosphatemia. Further studies are required to elucidate underlying pathophysiology and potential clinical consequences. Copyright © 2017 Endocrine Society

  20. Recent developments on the role of epigenetics in obesity and