Canine Models for Copper Homeostasis Disorders.

PubMed

Wu, Xiaoyan; Leegwater, Peter A J; Fieten, Hille

2016-02-04

Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted.

Canine Models for Copper Homeostasis Disorders

PubMed Central

Wu, Xiaoyan; Leegwater, Peter A. J.; Fieten, Hille

2016-01-01

Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted. PMID:26861285

Reye's Syndrome

MedlinePlus

... in children and teenagers who have an underlying fatty acid oxidation disorder. Fatty acid oxidation disorders are a group of inherited metabolic ... which the body is unable to break down fatty acids because an enzyme is missing or not working ...

Endothelial dysfunction in metabolic and vascular disorders.

PubMed

Polovina, Marija M; Potpara, Tatjana S

2014-03-01

Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

PubMed

Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

2016-05-01

Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The Role of Underlying Type 2 Diabetes Mellitus and Obesity in Ozone-Induced Pulmonary Injury and Metabolic Impairment

EPA Science Inventory

RATIONALE: A growing body of evidence indicates an association between air pollution exposure and metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). We have recently demonstrated that an acute exposure to ozone in metabolically normal rat strains produces h...

[Alkalosis].

PubMed

Kościelska, Malgorzata; Mieczkowski, Mariusz

2013-01-01

An elevation of arterial blood pH called alkalosis remains an underestimated condition in hospitalized patients. Serious alkalosis can be associated with high risk of death. The disorder can be caused by increased concentration of bicarbonate (metabolic alkalosis) or decreased concentration of carbon dioxide (respiratory alkalosis). In most cases of metabolic alkalosis it is generated by vomiting or diuretic use, whereas respiratory alkalosis is provoked by hyperventilation associated with respiratory or neurological disorder. Maintenance of metabolic alkalosis is possible only in patients with impaired renal base excretion which is most often produced by hypochloremia. In both respiratory and metabolic alkaloses treatment depends on the underlying factor. In hyperventilation syndrome is based on behavioral therapy. In most cases of metabolic alkalosis the administration of sodium and potassium chloride forms a substantial part of therapy.

Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism.

PubMed

Ardestani, Amin; Lupse, Blaz; Maedler, Kathrin

2018-05-05

The evolutionarily conserved Hippo pathway is a key regulator of organ size and tissue homeostasis. Its dysregulation is linked to multiple pathological disorders. In addition to regulating development and growth, recent studies show that Hippo pathway components such as MST1/2 and LATS1/2 kinases, as well as YAP/TAZ transcriptional coactivators, are regulated by metabolic pathways and that the Hippo pathway controls metabolic processes at the cellular and organismal levels in physiological and metabolic disease states such as obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), cardiovascular disorders, and cancer. In this review we summarize the connection between key Hippo components and metabolism, and how this interplay regulates cellular metabolism and metabolic pathways. The emerging function of Hippo in the regulation of metabolic homeostasis under physiological and pathological conditions is highlighted. Copyright © 2018 Elsevier Ltd. All rights reserved.

Metabolic control of oocyte development: linking maternal nutrition and reproductive outcomes

PubMed Central

Liu, Honglin; Gu, Xi; Boots, Christina; Moley, Kelle H.

2015-01-01

Obesity, diabetes, and related metabolic disorders are major health issues worldwide. As the epidemic of metabolic disorders continues, the associated medical comorbidities, including the detrimental impact on reproduction, increase as well. Emerging evidence suggests that the effects of maternal nutrition on reproductive outcomes are likely to be mediated, at least in part, by oocyte metabolism. Well-balanced and timed energy metabolism is critical for optimal development of oocytes. To date, much of our understanding of oocyte metabolism comes from the effects of extrinsic nutrients on oocyte maturation. In contrast, intrinsic regulation of oocyte development by metabolic enzymes, intracellular mediators, and transport systems is less characterized. Specifically, decreased acid transport proteins levels, increased glucose/lipid content and elevated reactive oxygen species in oocytes have been implicated in meiotic defects, organelle dysfunction and epigenetic alteration. Therefore, metabolic disturbances in oocytes may contribute to the diminished reproductive potential experienced by women with metabolic disorders. In-depth research is needed to further explore the underlying mechanisms. This review also discusses several approaches for metabolic analysis. Metabolomic profiling of oocytes, the surrounding granulosa cells, and follicular fluid will uncover the metabolic networks regulating oocyte development, potentially leading to the identification of oocyte quality markers and prevention of reproductive disease and poor outcomes in offspring. PMID:25280482

Peripheral blood gene expression profiles in metabolic syndrome, coronary artery disease and type 2 diabetes.

PubMed

Grayson, B L; Wang, L; Aune, T M

2011-07-01

To determine if individuals with metabolic disorders possess unique gene expression profiles, we compared transcript levels in peripheral blood from patients with coronary artery disease (CAD), type 2 diabetes (T2D) and their precursor state, metabolic syndrome to those of control (CTRL) subjects and subjects with rheumatoid arthritis (RA). The gene expression profile of each metabolic state was distinguishable from CTRLs and correlated with other metabolic states more than with RA. Of note, subjects in the metabolic cohorts overexpressed gene sets that participate in the innate immune response. Genes involved in activation of the pro-inflammatory transcription factor, NF-κB, were overexpressed in CAD whereas genes differentially expressed in T2D have key roles in T-cell activation and signaling. Reverse transcriptase PCR validation confirmed microarray results. Furthermore, several genes differentially expressed in human metabolic disorders have been previously shown to participate in inflammatory responses in murine models of obesity and T2D. Taken together, these data demonstrate that peripheral blood from individuals with metabolic disorders display overlapping and non-overlapping patterns of gene expression indicative of unique, underlying immune processes.

Acute hepatic decompensation precipitated by pregnancy-related catabolic stress: a rare mimic of acute liver failure.

PubMed

Sinclair, Marie; Ket, Shara; Testro, Adam; Gow, Paul J; Angus, Peter W

2014-02-01

Abnormal liver function tests are common in pregnancy; however, liver failure is rare. Pregnancy is a catabolic state that can precipitate illness in patients with underlying metabolic disorders. A 19-year-old woman presented at 14 weeks of gestation with an alanine transaminase of 2,252 international units/L (less than 30), an international normalized ratio of 6.9 (0.9-1.2), and an ammonia of 58 micromole/L (11-51 micromole/L). No cause was identified on routine investigations including liver biopsy. Biochemical and clinical deterioration prompted investigation for a metabolic disorder. Urinary orotic acid was elevated, consistent with the urea cycle disorder type 1 citrullinemia. Appropriate management (arginine supplementation and dietary protein restriction) led to rapid improvement and later delivery of a healthy neonate. This is an unusual presentation that reminds us of the importance of considering metabolic disorders during the catabolic stress of pregnancy.

Application of exome sequencing in the search for genetic causes of rare disorders of copper metabolism.

PubMed

Fuchs, Sabine A; Harakalova, Magdalena; van Haaften, Gijs; van Hasselt, Peter M; Cuppen, Edwin; Houwen, Roderick H J

2012-07-01

The genetic defect in a number of rare disorders of metal metabolism remains elusive. The limited number of patients with these disorders impedes the identification of the causative gene through positional cloning, which requires numerous families with multiple affected individuals. However, with next-generation sequencing all coding DNA (exomes) or whole genomes of patients can be sequenced to identify genes that are consistently mutated in patients. With this strategy only a limited number of patients and/or pedigrees is needed, bringing the elucidation of the genetic cause of even very rare diseases within reach. The main challenge associated with whole exome sequencing is the identification of the disease-causing mutation(s) among abundant genetic candidate variants. We describe several strategies to manage this data wealth, including comparison with control databases, increasing the number of patients and controls, and reducing the genomic region under investigation through homozygosity mapping. In this review we introduce a number of rare disorders of copper metabolism, with a suspected but yet unknown monogenetic cause, as an attractive target for this strategy. We anticipate that use of these novel techniques will identify the basic defect in the disorders described in this review, as well as in other genetic disorders of metal metabolism, in the next few years.

Hypophosphatemic rickets: Revealing Novel Control Points for Phosphate Homeostasis

PubMed Central

White, Kenneth E.; Hum, Julia M.; Econs, Michael J.

2014-01-01

Rapid and somewhat surprising advances have recently been made towards understanding the molecular mechanisms causing heritable disorders of hypophosphatemia. The results of clinical, genetic, and translational studies have interwoven novel concepts underlying the endocrine control of phosphate metabolism, with far-reaching implications for treatment of both rare, Mendelian diseases as well as common disorders of blood phosphate excess such as chronic kidney disease (CKD). In particular, diseases caused by changes in the expression and proteolytic control of the phosphaturic hormone Fibroblast growth factor-23 (FGF23) have come to the forefront in terms of directing new models explaining mineral metabolism. These hypophosphatemic disorders, as well as others resulting from independent defects in phosphate transport or metabolism, will be reviewed herein, and implications for emerging therapeutic strategies based upon these new findings will be discussed. PMID:24980542

The Role of Androgen Excess in Metabolic Dysfunction in Women : Androgen Excess and Female Metabolic Dysfunction.

PubMed

Escobar-Morreale, Héctor F

2017-01-01

Polycystic ovary syndrome (PCOS) is characterized by the association of androgen excess with chronic oligoovulation and/or polycystic ovarian morphology, yet metabolic disorders and classic and nonclassic cardiovascular risk factors cluster in these women from very early in life. This chapter focuses on the mechanisms underlying the association of PCOS with metabolic dysfunction, focusing on the role of androgen excess on the development of visceral adiposity and adipose tissue dysfunction.

Acute fatal metabolic complications in alkaptonuria.

PubMed

Davison, A S; Milan, A M; Gallagher, J A; Ranganath, L R

2016-03-01

Alkaptonuria (AKU) is a rare inherited metabolic disorder of tyrosine metabolism that results from a defect in an enzyme called homogentisate 1,2-dioxygenase. The result of this is that homogentisic acid (HGA) accumulates in the body. HGA is central to the pathophysiology of this disease and the consequences observed; these include spondyloarthropathy, rupture of ligaments/muscle/tendons, valvular heart disease including aortic stenosis and renal stones. While AKU is considered to be a chronic progressive disorder, it is clear from published case reports that fatal acute metabolic complications can also occur. These include oxidative haemolysis and methaemoglobinaemia. The exact mechanisms underlying the latter are not clear, but it is proposed that disordered metabolism within the red blood cell is responsible for favouring a pro-oxidant environment that leads to the life threatening complications observed. Herein the role of red blood cell in maintaining the redox state of the body is reviewed in the context of AKU. In addition previously reported therapeutic strategies are discussed, specifically with respect to why reported treatments had little therapeutic effect. The potential use of nitisinone for the management of patients suffering from the acute metabolic decompensation in AKU is proposed as an alternative strategy.

Growth hormone deficiency in a patient with mitochondrial disease.

PubMed

Rocha, Vera; Rocha, Dalila; Santos, Helena; Sales Marques, Jorge

2015-09-01

Mitochondrial respiratory chain (MRC) disorders, defined as primary diseases of the oxidative phosphorylation system, are a protean group of metabolic disorders, difficult to diagnose and classify. The diagnosis is complex and requires the integration of information obtained by clinical, laboratory testing, imaging and muscle biopsy. They may be associated with endocrine disorders, including hypothyroidism, diabetes mellitus, hyperinsulinemia and growth hormone (GH) deficiency. We describe a case of five years old male with polymalformative syndrome with a systemic involvement. At 6 months of age, he was sent to metabolic consultation because of facial dysmorphy and short stature. During the investigation it was diagnosed at the boy a growth hormone deficiency and because of his multisystemic involvement, muscle biopsy was carried out and showed reduced activity of complex II (38%) of the mitochondrial respiratory chain. Currently, the boy is under GH therapy with growth in the 5th percentile and coenzime Q10. Mitochondrial biology is one of the fastest growing areas in genetics and medicine. Disturbances in mitochondrial metabolism are now known to play a role not only in rare childhood diseases, but also in many common diseases of aging. In mitochondrial disorders, short stature is a common symptom, but its underlying lesion, growth hormone deficiency, is rarely investigated.

Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes.

PubMed

Wang, Xiaoting; Ota, Naruhisa; Manzanillo, Paolo; Kates, Lance; Zavala-Solorio, Jose; Eidenschenk, Celine; Zhang, Juan; Lesch, Justin; Lee, Wyne P; Ross, Jed; Diehl, Lauri; van Bruggen, Nicholas; Kolumam, Ganesh; Ouyang, Wenjun

2014-10-09

The connection between an altered gut microbiota and metabolic disorders such as obesity, diabetes, and cardiovascular disease is well established. Defects in preserving the integrity of the mucosal barriers can result in systemic endotoxaemia that contributes to chronic low-grade inflammation, which further promotes the development of metabolic syndrome. Interleukin (IL)-22 exerts essential roles in eliciting antimicrobial immunity and maintaining mucosal barrier integrity within the intestine. Here we investigate the connection between IL-22 and metabolic disorders. We find that the induction of IL-22 from innate lymphoid cells and CD4(+) T cells is impaired in obese mice under various immune challenges, especially in the colon during infection with Citrobacter rodentium. While innate lymphoid cell populations are largely intact in obese mice, the upregulation of IL-23, a cytokine upstream of IL-22, is compromised during the infection. Consequently, these mice are susceptible to C. rodentium infection, and both exogenous IL-22 and IL-23 are able to restore the mucosal host defence. Importantly, we further unveil unexpected functions of IL-22 in regulating metabolism. Mice deficient in IL-22 receptor and fed with high-fat diet are prone to developing metabolic disorders. Strikingly, administration of exogenous IL-22 in genetically obese leptin-receptor-deficient (db/db) mice and mice fed with high-fat diet reverses many of the metabolic symptoms, including hyperglycaemia and insulin resistance. IL-22 shows diverse metabolic benefits, as it improves insulin sensitivity, preserves gut mucosal barrier and endocrine functions, decreases endotoxaemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. In summary, we identify the IL-22 pathway as a novel target for therapeutic intervention in metabolic diseases.

Current perspectives on the health risks associated with the consumption of advanced glycation end products: recommendations for dietary management

PubMed Central

Palimeri, Sotiria; Palioura, Eleni; Diamanti-Kandarakis, Evanthia

2015-01-01

Advanced glycation end products (AGEs) constitute a complex group of compounds produced endogenously during the aging process and under conditions of hyperglycemia and oxidative stress. AGEs also have an emerging exogenous origin. Cigarette smoke and diet are the two main exogenous sources of AGEs (glycotoxins). Modern Western diets are rich in AGEs which have been implicated in the pathogenesis of several metabolic and degenerative disorders. Accumulating evidence underlies the beneficial effect of the dietary restriction of AGEs not only in animal studies but also in patients with diabetic complications and metabolic diseases. This article reviews the evidence linking dietary glycotoxins to several disorders from diabetic complications and renal failure to liver dysfunction, female reproduction, eye and cognitive disorders as well as cancer. Furthermore, strategies for AGE reduction are discussed with a focus on dietary modification. PMID:26366100

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

PubMed Central

Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

2014-01-01

Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities.

PubMed

Singh, Neena; Haldar, Swati; Tripathi, Ajai K; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K; Singh, Ajay

2014-03-10

Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders.

Theacrine protects against nonalcoholic fatty liver disease by regulating acylcarnitine metabolism.

PubMed

Wang, Guo-En; Li, Yi-Fang; Zhai, Yu-Jia; Gong, Lian; Tian, Jing-Yu; Hong, Mo; Yao, Nan; Wu, Yan-Ping; Kurihara, Hiroshi; He, Rong-Rong

2018-05-01

Acylcarnitine metabolism disorder contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). There are, however, few ideal medications for NAFLD, which work by targeting acylcarnitine metabolism. The aim of this study was to investigate the protective effects of theacrine, a rare purine alkaloid isolated from Camellia assamica var. kucha, against acylcarnitine metabolism disorder in NAFLD. The pharmacological activities of theacrine were studied using high-fat diet (HFD)-fed ApoE-/- and C57BL/6 J mice models. Oleate-treated HepG2 and L-02 cells were used to investigate the molecular mechanism of theacrine on acylcarnitine metabolism. The target of theacrine was confirmed in vitro as the blockade of sirtuin 3 (SIRT3) and protein kinase A. Theacrine inhibits hepatic steatosis and liver inflammation and improves energy expenditure in HFD-fed mice. Theacrine ameliorates acylcarnitine metabolism disorder in HFD-fed mice and oleate-treated hepatocytes by improving fatty acid oxidation. The underlying mechanism involves theacrine's activation of the mitochondrial deacetylase SIRT3 and consequently, the increased activity of long-chain acyl coenzyme A dehydrogenase (LCAD) through deacetylation. Theacrine promotes acylcarnitine metabolism in NAFLD through the SIRT3/LCAD signaling pathway. The target of theacrine's activities on NAFLD is identified as SIRT3. Copyright © 2018. Published by Elsevier Inc.

Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption.

PubMed

Calo, Nicolas; Ramadori, Pierluigi; Sobolewski, Cyril; Romero, Yannick; Maeder, Christine; Fournier, Margot; Rantakari, Pia; Zhang, Fu-Ping; Poutanen, Matti; Dufour, Jean-François; Humar, Bostjan; Nef, Serge; Foti, Michelangelo

2016-11-01

miR-21 is an oncomir highly upregulated in hepatocellular carcinoma and in early stages of liver diseases characterised by the presence of steatosis. Whether upregulation of miR-21 contributes to hepatic metabolic disorders and their progression towards cancer is unknown. This study aims at investigating the role of miR-21/miR-21* in early stages of metabolic liver disorders associated with diet-induced obesity (DIO). Constitutive miR-21/miR-21* knockout (miR21KO) and liver-specific miR-21/miR-21* knockout (LImiR21KO) mice were generated. Mice were then fed with high-fat diet (HFD) and alterations of the lipid and glucose metabolism were investigated. Serum and ex vivo explanted liver tissue were analysed. Under normal breeding conditions and standard diet, miR-21/miR-21* deletion in mice was not associated with any detectable phenotypic alterations. However, when mice were challenged with an obesogenic diet, glucose intolerance, steatosis and adiposity were improved in mice lacking miR-21/miR-21* . Deletion of miR-21/miR-21* specifically in hepatocytes led to similar improvements in mice fed an HFD, indicating a crucial role for hepatic miR-21/miR-21* in metabolic disorders associated with DIO. Further molecular analyses demonstrated that miR-21/miR-21* deletion in hepatocytes increases insulin sensitivity and modulates the expression of multiple key metabolic transcription factors involved in fatty acid uptake, de novo lipogenesis, gluconeogenesis and glucose output. Hepatic miR-21/miR-21* deficiency prevents glucose intolerance and steatosis in mice fed an obesogenic diet by altering the expression of several master metabolic regulators. This study points out miR-21/miR-21 * as a potential therapeutic target for non-alcoholic fatty liver disease and the metabolic syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Stress transgenerationally programs metabolic pathways linked to altered mental health.

PubMed

Kiss, Douglas; Ambeskovic, Mirela; Montina, Tony; Metz, Gerlinde A S

2016-12-01

Stress is among the primary causes of mental health disorders, which are the most common reason for disability worldwide. The ubiquity of these disorders, and the costs associated with them, lends a sense of urgency to the efforts to improve prediction and prevention. Down-stream metabolic changes are highly feasible and accessible indicators of pathophysiological processes underlying mental health disorders. Here, we show that remote and cumulative ancestral stress programs central metabolic pathways linked to mental health disorders. The studies used a rat model consisting of a multigenerational stress lineage (the great-great-grandmother and each subsequent generation experienced stress during pregnancy) and a transgenerational stress lineage (only the great-great-grandmother was stressed during pregnancy). Urine samples were collected from adult male F4 offspring and analyzed using 1 H NMR spectroscopy. The results of variable importance analysis based on random variable combination were used for unsupervised multivariate principal component analysis and hierarchical clustering analysis, as well as metabolite set enrichment analysis (MSEA) and pathway analysis. We identified distinct metabolic profiles associated with the multigenerational and transgenerational stress phenotype, with consistent upregulation of hippurate and downregulation of tyrosine, threonine, and histamine. MSEA and pathway analysis showed that these metabolites are involved in catecholamine biosynthesis, immune responses, and microbial host interactions. The identification of metabolic signatures linked to ancestral programming assists in the discovery of gene targets for future studies of epigenetic regulation in pathogenic processes. Ultimately, this research can lead to biomarker discovery for better prediction and prevention of mental health disorders.

Disorders of Amino Acid Metabolism

MedlinePlus

... Drugs Ear, Nose, and Throat Disorders Eye Disorders Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic ... Drugs Ear, Nose, and Throat Disorders Eye Disorders Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic ...

CRHR1 genotypes, neural circuits and the diathesis for anxiety and depression.

PubMed

Rogers, J; Raveendran, M; Fawcett, G L; Fox, A S; Shelton, S E; Oler, J A; Cheverud, J; Muzny, D M; Gibbs, R A; Davidson, R J; Kalin, N H

2013-06-01

The corticotrophin-releasing hormone (CRH) system integrates the stress response and is associated with stress-related psychopathology. Previous reports have identified interactions between childhood trauma and sequence variation in the CRH receptor 1 gene (CRHR1) that increase risk for affective disorders. However, the underlying mechanisms that connect variation in CRHR1 to psychopathology are unknown. To explore potential mechanisms, we used a validated rhesus macaque model to investigate association between genetic variation in CRHR1, anxious temperament (AT) and brain metabolic activity. In young rhesus monkeys, AT is analogous to the childhood risk phenotype that predicts the development of human anxiety and depressive disorders. Regional brain metabolism was assessed with (18)F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography in 236 young, normally reared macaques that were also characterized for AT. We show that single nucleotide polymorphisms (SNPs) affecting exon 6 of CRHR1 influence both AT and metabolic activity in the anterior hippocampus and amygdala, components of the neural circuit underlying AT. We also find evidence for association between SNPs in CRHR1 and metabolism in the intraparietal sulcus and precuneus. These translational data suggest that genetic variation in CRHR1 affects the risk for affective disorders by influencing the function of the neural circuit underlying AT and that differences in gene expression or the protein sequence involving exon 6 may be important. These results suggest that variation in CRHR1 may influence brain function before any childhood adversity and may be a diathesis for the interaction between CRHR1 genotypes and childhood trauma reported to affect human psychopathology.

Insomnia of childhood.

PubMed

Lipton, Jonathan; Becker, Ronald E; Kothare, Sanjeev V

2008-12-01

Insomnia is a major public health problem and is the most common sleep disturbance in both adults and children. The causes of sleeplessness are age-dependent and have potentially enormous effects on cognitive development, behavior, family dynamics, and the metabolic health of children. Here we review the epidemiology, cause, pathophysiology, and clinical approach to pediatric insomnia. Normal sleep is crucial for brain function, behavior, and normal metabolism. Consistently, sleep loss has been linked to behavioral and attention problems, impaired learning and memory, obesity, and psychiatric disorders. The neurological mechanisms that govern sleep initiation and maintenance are poorly understood. The types of insomnia are age-dependent and can occur as primary disorders, or in the context of another primary sleep disorder such as restless legs syndrome, or secondary to another underlying medical condition. Children with chronic diseases and especially children with neurodevelopmental disorders are at particular risk of insomnia. Pediatric insomnia is common and is a source of potential psychophysiological stress to both children and their caregivers. The causes of insomnia are various. Pediatricians should have a working knowledge of the causes of sleeplessness in order to promptly curtail the chronic effects of sleep loss and effectively screen for underlying, potentially treatable disorders.

Carbohydrate Metabolism Disorders

MedlinePlus

Metabolism is the process your body uses to make energy from the food you eat. Food is ... disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally ...

Magnesium isoglycyrrhizinate blocks fructose-induced hepatic NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder.

PubMed

Zhao, Xiao-Juan; Yang, Yan-Zi; Zheng, Yan-Jing; Wang, Shan-Chun; Gu, Hong-Mei; Pan, Ying; Wang, Shui-Juan; Xu, Hong-Jiang; Kong, Ling-Dong

2017-08-15

Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels. Furthermore, magnesium isoglycyrrhizinate modulated lipid metabolism-related genes characterized by up-regulating peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyl transferase-1 (CPT-1), and down-regulating sensor for fatty acids to control-1 (SREBP-1) and stearoyl-CoA desaturase 1 (SCD-1) in the liver of fructose-fed rats, resulting in the reduction of triglyceride and total cholesterol levels. These effective actions were further confirmed in fructose-exposed BRL-3A and HepG2 cells. The molecular mechanisms underpinning these observations suggest that magnesium isoglycyrrhizinate may inhibit NF-κB/NLRP3 inflammasome activation to reduce immunological-inflammatory response, which in turn may prevent liver lipid metabolic disorder and accumulation under high fructose condition. Thus, blockade of NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder by magnesium isoglycyrrhizinate may be the potential therapeutic approach for improving fructose-induced liver injury with metabolic syndrome in clinic. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

PubMed Central

Assies, J; Mocking, R J T; Lok, A; Ruhé, H G; Pouwer, F; Schene, A H

2014-01-01

Objective Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive responses, might underlie comorbidity between CVD and psychiatric disorders. Method We conducted a literature search and integrated data in a narrative review. Results Oxidative stress, mainly generated in mitochondria, is implicated in both psychiatric and cardiovascular pathophysiology. Oxidative stress affects the intrinsically linked FA and 1-C cycle metabolism: FAs decrease in chain length and unsaturation (particularly omega-3 polyunsaturated FAs), and lipid peroxidation products increase; the 1-C cycle shifts from the methylation to transsulfuration pathway (lower folate and higher homocysteine and antioxidant glutathione). Interestingly, corresponding alterations were reported in psychiatric disorders and CVD. Potential mechanisms through which FA and 1-C cycle metabolism may be involved in brain (neurocognition, mood regulation) and cardiovascular system functioning (inflammation, thrombosis) include membrane peroxidizability and fluidity, eicosanoid synthesis, neuroprotection and epigenetics. Conclusion While oxidative-stress-induced alterations in FA and 1-C metabolism may initially enhance oxidative stress resistance, persisting chronically, they may cause damage possibly underlying (co-occurrence of) psychiatric disorders and CVD. This might have implications for research into diagnosis and (preventive) treatment of (CVD in) psychiatric patients. PMID:24649967

Metabolic Stress and Disorders Related to Alterations in Mitochondrial Fission or Fusion

PubMed Central

Babbar, Mansi; Sheikh, M. Saeed

2014-01-01

Mitochondrial morphology and metabolism play an important role in cellular homeostasis. Recent studies have shown that the fidelity of mitochondrial morphology is important in maintaining mitochondrial shape, number, size, membrane potential, ATP synthesis, mtDNA, motility, signaling, quality control, response to cellular stress, mitophagy and apoptosis. This article provides an overview of the current state of knowledge of the fission and fusion machinery with a focus on the mechanisms underlying the regulation of the mitochondrial morphology and cellular energy state. Several lines of evidence indicate that dysregulation of mitochondrial fission or fusion is associated with mitochondrial dysfunction, which in turn impacts mitophagy and apoptosis. Metabolic disorders are also associated with dysregulation of fission or fusion and the available lines of evidence point to a bidirectional interplay between the mitochondrial fission or fusion reactions and bioenergetics. Clearly, more in-depth studies are needed to fully elucidate the mechanisms that control mitochondrial fission and fusion. It is envisioned that the outcome of such studies will improve the understanding of the molecular basis of related metabolic disorders and also facilitate the development of better therapeutics. PMID:24533171

Androgens and polycystic ovary syndrome.

PubMed

Nisenblat, Vicki; Norman, Robert J

2009-06-01

Polycystic ovary syndrome (PCOS) is a common complex endocrine genetic disorder, which involves overproduction of androgens, leading to heterogeneous range of symptoms and associated with increased metabolic and cardiovascular morbidity. This review focuses on androgen biosynthesis, use, metabolism in PCOS and clinical consequences of hyperandrogenism. Controversial definition of the disorder and different phenotypic subgroups present a challenge for clinical and basic research. Further investigation of different phenotypes highlights the fact that PCOS probably represents a group of disorders with different etiologies. Prenatal androgen exposure and adolescent studies suggest early in life androgen excess as initiating factor of PCOS, but insufficient evidence available to confirm this hypothesis. Various intracellular signaling pathways implicated in PCOS steroidogenesis and in androgen action have been studied, however, PCOS pathogenesis remains obscure. Growing evidence links androgens with pathophysiology of PCOS and metabolic derangements. Despite intensive investigation, etiology and underlying mechanisms of PCOS remain unclear, warranting further investigation. Better understanding of molecular and genetic basis might lead to invention of novel therapeutic approaches. Long-term interventional studies that lower androgen levels in women with hyperandrogenism might protect against metabolic and cardiovascular comorbidities are needed.

Assessment and Treatment in Autism Spectrum Disorders: A Focus on Genetics and Psychiatry

PubMed Central

Butler, Merlin G.; Youngs, Erin L.; Roberts, Jennifer L.; Hellings, Jessica A.

2012-01-01

Autism spectrum disorders (ASDs) are neurobehavioral disorders characterized by abnormalities in three behavioral domains including social interaction, impaired communication, and repetitive stereotypic behaviors. ASD affects approximately 1% of children and is on the rise with significant genetic mechanisms underlying these disorders. We review the current understanding of the role of genetic and metabolic factors contributing to ASD with the use of new genetic technology. Fifty percent is diagnosed with chromosomal abnormalities, small DNA deletions/duplications, single-gene conditions, or metabolic disturbances. Genetic evaluation is discussed along with psychiatric treatment and approaches for selection of medication to treat associated challenging behaviors or comorbidities seen in ASD. We emphasize the importance of prioritizing treatment based on target symptom clusters and in what order for individuals with ASD, as the treatment may vary from patient to patient. PMID:22934170

[Metabolic alkalosis despite hyperlactatemia and hypercapnia. Interpretation and therapy with help of the Stewart concept].

PubMed

Chappell, D; Hofmann-Kiefer, K; Jacob, M; Conzen, P; Rehm, M

2008-02-01

Acid-base disturbances are commonly found in critically ill patients and are often associated with fatal complications. The basis of a successful treatment is a thorough understanding of the causes of these disorders. The "classical methods" to explain acid-base disorders--pH, base excess and bicarbonate concentration--mostly do not provide a causal correlation to the underlying pathology. An unusual case of a combined respiratory-metabolic disorder with hyperlactatemia and hypercapnia is presented. An acidosis masked by hypochloremic and hypoalbuminemic alkalosis was identified with the help of Stewart's concept and finally permitted a successful therapy. The modern Stewart concept provides enhanced information, enabling an exact diagnosis and causal therapy even in complex cases.

Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

PubMed

Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

2017-01-01

Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Use of diphosphonates to correct disorders in calcium metabolism and mineral composition of bone tissue with 60-day hypokinesia in rats

NASA Technical Reports Server (NTRS)

Morukov, B. V.; Zaychik, V. YE.; Ivanov, V. M.; Orlov, O. I.

1988-01-01

Compounds of the diphosphonate group suppress bone resorption and bone tissue metabolism, from which it was assumed that they can be used for the prevention of osteoporosis and disorders of calcium homeostasis in humans during space flight. Two compounds of this group were used for preventive purposes in 60 day hypokinesia in rats. The results showed that diphosphonates have a marked effect on calcium metabolism and the condition of the bone tissues under conditions of long term hypokinesia: they reduce the content of ionized calcium in blood, delay the loss of calcium and phosphorus by the bone tissue, and to a considerable degree prevent reduction of bone density. This confirms the possibility of using compounds of this group for correcting and preventing changes of bone tissue and mineral metabolism during long term hypokinesia.

Should waist circumference be used to identify metabolic disorders than BMI in South Korea?

PubMed

Lee, S-K

2010-11-01

Although indicators of central obesity have been suggested as a better alternative to body mass index (BMI), yet mixed results exist. This study examined whether waist circumference (WC) was better in identifying metabolic disorders than BMI at two time points. This study used nationally representative 1998 and 2005 Korea National Health and Nutrition Examination Survey data sets. Odds ratios from logistic regressions and area under the curves (AUC) were calculated. BMI and WC showed similar level of odds ratios (1.1-1.6) to diabetes, hypertension, dyslipidemia and having two or three metabolic syndrome criteria. The AUC comparison, however, indicated that, in only women, WC was a better discriminator for diabetes, hypertension and having two or three metabolic syndrome criteria. No meaningful differences were found between 1998 and 2005. Prospective studies to weigh practical and clinical relevance are needed to assert the use of WC over BMI in clinical and public health settings.

Chilling-related cell damage of apple (Malus x domestica Borkh.) fruit cortical tissue impacts antioxidant, lipid, and phenolic metabolism

USDA-ARS?s Scientific Manuscript database

‘Soggy breakdown’ (SB) is an internal disorder of ‘Honeycrisp’ apple (Malus × domestica Borkh.) fruit which occurs during low temperature storage. The disorder is a chilling injury (CI) in which visible symptoms typically appear after several weeks of storage, but information about the underlying m...

Metabolic Profiles in Ovine Carotid Arteries with Developmental Maturation and Long-Term Hypoxia

PubMed Central

Goyal, Ravi; Longo, Lawrence D.

2015-01-01

Background Long-term hypoxia (LTH) is an important stressor related to health and disease during development. At different time points from fetus to adult, we are exposed to hypoxic stress because of placental insufficiency, high-altitude residence, smoking, chronic anemia, pulmonary, and heart disorders, as well as cancers. Intrauterine hypoxia can lead to fetal growth restriction and long-term sequelae such as cognitive impairments, hypertension, cardiovascular disorders, diabetes, and schizophrenia. Similarly, prolonged hypoxic exposure during adult life can lead to acute mountain sickness, chronic fatigue, chronic headache, cognitive impairment, acute cerebral and/or pulmonary edema, and death. Aim LTH also can lead to alteration in metabolites such as fumarate, 2-oxoglutarate, malate, and lactate, which are linked to epigenetic regulation of gene expression. Importantly, during the intrauterine life, a fetus is under a relative hypoxic environment, as compared to newborn or adult. Thus, the changes in gene expression with development from fetus to newborn to adult may be as a consequence of underlying changes in the metabolic profile because of the hypoxic environment along with developmental maturation. To examine this possibility, we examined the metabolic profile in carotid arteries from near-term fetus, newborn, and adult sheep in both normoxic and long-term hypoxic acclimatized groups. Results Our results demonstrate that LTH differentially regulated glucose metabolism, mitochondrial metabolism, nicotinamide cofactor metabolism, oxidative stress and antioxidants, membrane lipid hydrolysis, and free fatty acid metabolism, each of which may play a role in genetic-epigenetic regulation. PMID:26110419

Metabolic features of the cell danger response.

PubMed

Naviaux, Robert K

2014-05-01

The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis. © 2013. Published by Elsevier B.V. All rights reserved.

The scent of disease: volatile organic compounds of the human body related to disease and disorder.

PubMed

Shirasu, Mika; Touhara, Kazushige

2011-09-01

Hundreds of volatile organic compounds (VOCs) are emitted from the human body, and the components of VOCs usually reflect the metabolic condition of an individual. Therefore, contracting an infectious or metabolic disease often results in a change in body odour. Recent progresses in analytical techniques allow rapid analyses of VOCs derived from breath, blood, skin and urine. Disease-specific VOCs can be used as diagnostic olfactory biomarkers of infectious diseases, metabolic diseases, genetic disorders and other kinds of diseases. Elucidation of pathophysiological mechanisms underlying production of disease-specific VOCs may provide novel insights into therapeutic approaches for treatments for various diseases. This review summarizes the current knowledge on chemical and clinical aspects of body-derived VOCs, and provides a brief outlook at the future of olfactory diagnosis.

Kidney Calculi: Pathophysiology and as a Systemic Disorder.

PubMed

Shadman, Arash; Bastani, Bahar

2017-05-01

The pathophysiology of urinary stone formation is complex, involving a combination of metabolic, genetic, and environmental factors. Over the past decades, remarkable advances have been emerged in the understanding of the pathogenesis, diagnosis, and treatment of calcium kidney calculi. For this review, both original and review articles were found via PubMed search on pathophysiology, diagnosis, and management of urinary calculi. These resources were integrated with the authors' knowledge of the field. Nephrolithiasis is suggested to be associated with systemic disorders, including chronic kidney insufficiency, hematologic malignancies, endocrine disorders, autoimmune diseases, inflammatory bowel diseases, bone loss and fractures, hypertension, type 2 diabetes mellitus, metabolic syndrome, and vascular diseases like coronary heart diseases and most recently ischemic strokes. This is changing the perspective of nephrolithiasis from an isolated disorder to a systemic disease that justifies further research in understanding the underlying mechanisms and elaborating diagnostic-therapeutic options.

A predisposition for allergies predicts subsequent hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder: a nationwide longitudinal study.

PubMed

Chen, Mu-Hong; Li, Cheng-Ta; Lin, Wei-Chen; Wei, Hang-Tin; Chang, Wen-Han; Chen, Tzeng-Ji; Pan, Tai-Long; Su, Tung-Ping; Bai, Ya-Mei

2014-10-01

Previous studies have shown that both severe mental disorders (schizophrenia and bipolar disorder) and atopic diseases were associated with an increased risk of metabolic syndrome. However, the role of atopy/the predisposition for allergies in the development of metabolic syndrome is still unknown among those with severe mental disorders. Using the Taiwan National Health Insurance Research Database, 5826 patients with schizophrenia or bipolar disorder (1908 with a predisposition for allergies and 3918 without) were enrolled between 1998 and 2008. Those who developed hypertension, dyslipidemia, and/or diabetes mellitus were identified during the follow-up to the end of 2011. A predisposition for allergies increased the risk of developing hypertension (HR: 1.67), dyslipidemia (HR: 1.82), and diabetes mellitus (HR: 1.37) in later life among those with severe mental disorders. A dose-dependent relationship was noted between having more atopic comorbidities and a greater likelihood of hypertension (1 atopic disease: HR: 1.60; ≧ 2 atopic comorbidities: HR: 1.87), dyslipidemia (HR: 1.73; HR: 2.12), and diabetes mellitus (HR: 1.26; HR: 1.69). A predisposition for allergies was an independent risk factor for hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder. Further studies would be required to elucidate the underlying pathophysiology among atopy, schizophrenia, bipolar disorder, and metabolic syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

Sleep and metabolism: role of hypothalamic neuronal circuitry.

PubMed

Rolls, Asya; Schaich Borg, Jana; de Lecea, Luis

2010-10-01

Sleep and metabolism are intertwined physiologically and behaviorally, but the neural systems underlying their coordination are still poorly understood. The hypothalamus is likely to play a major role in the regulation sleep, metabolism, and their interaction. And increasing evidence suggests that hypocretin cells in the lateral hypothalamus may provide particularly important contributions. Here we review: 1) direct interactions between biological arousal and metabolic systems in the hypothalamus, and 2) indirect interactions between these two systems mediated by stress or reward, emphasizing the role of hypocretins. An increased understanding of the mechanisms underlying these interactions may provide novel approaches for the treatment of patients with sleep disorders and obesity, as well as suggest new therapeutic strategies for symptoms of aging, stress, or addiction. Copyright © 2010. Published by Elsevier Ltd.

Cellular energy metabolism in T-lymphocytes.

PubMed

Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

2015-01-01

Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

[Circadian blood pressure variation under several pathophysiological conditions including secondary hypertension].

PubMed

Imai, Yutaka; Hosaka, Miki; Satoh, Michihiro

2014-08-01

Abnormality of circadian blood pressure (BP) variation, i.e. non-dipper, riser, nocturnal hypertension etc, is brought by several pathophysiological conditions especially by secondary hypertension. These pathophysiological conditions are classified into several categories, i.e. disturbance of autonomic nervous system, metabolic disorder, endocrine disorder, disorder of Na and water excretion (e.g. sodium sensitivity), severe target organ damage and ischemia, cardiovascular complications and drug induced hypertension. Each pathophysiological condition which brings disturbance of circadian BP variation is included in several categories, e.g. diabetes mellitus is included in metabolic disorder, autonomic imbalance, sodium sensitivity and endocrine disorder. However, it seems that unified principle of the genesis of disturbance of circadian BP variation in many pathophysiological conditions is autonomic imbalance. Thus, it is concluded that disturbance of circadian BP variation is not purposive biological behavior but the result of autonomic imbalance which looks as if compensatory reaction such as exaggerated Na-water excretion during night in patient with Na-water retention who reveals disturbed circadian BP variation.

Application of research findings and summary of research needs: Bud Britton Memorial Symposium on Metabolic Disorders of Feedlot Cattle.

PubMed

Galyean, M L; Eng, K S

1998-01-01

Updated research findings with acidosis, feedlot bloat, liver abscesses, and sudden death syndromes were presented at the Bud Britton Memorial Symposium on Metabolic Disorders of Feedlot Cattle. Possible industry applications include the need to establish guidelines for use of clostridial vaccines in feedlot cattle, further assessment of the relationship between acidosis and polioencephalomalacia, examination of the effects of various ionophores on the incidence of metabolic disorders, and evaluation of the effects of feed bunk management and limit- and restricted-feeding programs on the incidence of metabolic disorders. A multidisciplinary approach among researchers, consulting nutritionists and veterinarians, and feedlot managers will be required for effective progress in research and in the application of research findings. Areas suggested for further research include 1) assessment of feed consumption patterns and social behavior of cattle in large-pen, feedlot settings; 2) evaluation of the relationship between feed intake management systems (feed bunk management programs, limit- and programmed-feeding) and the incidence of metabolic disorders, including delineation of the role of variability in feed intake in the etiology of such disorders; 3) efforts to improve antemortem and postmortem diagnosis, and to establish standardized regional or national epidemiological databases for various metabolic disorders; 4) ascertaining the accuracy of diagnosis of metabolic disorders and determining the relationship of previous health history of animals to the incidence of metabolic disorders; 5) further defining ruminal and intestinal microbiology as it relates to metabolic disorders and deeper evaluation of metabolic changes that occur with such disorders; 6) continued appraisal of the effects of grain processing and specific feed ingredients and nutrients on metabolic disorders, and development of new feed additives to control or prevent these disorders; and 7) application of biotechnology to develop grain varieties with altered nutrient degradation profiles that decrease the propensity for disastrous acid loads in the rumen, feed-grade enzymes and probiotics that modify nutrient digestion or microbial profiles in the rumen and intestine, and specific strains of ruminal bacteria and protozoa that alter ruminal and metabolic conditions that may precipitate metabolic disorders.

Identification of diagnostic biomarkers and metabolic pathway shifts of heat-stressed lactating dairy cows.

PubMed

Tian, He; Wang, Weiyu; Zheng, Nan; Cheng, Jianbo; Li, Songli; Zhang, Yangdong; Wang, Jiaqi

2015-07-01

Controlling heat stress (HS) is a global challenge for the dairy industry. However, simple and reliable biomarkers that aid the diagnoses of HS-induced metabolic disorders have not yet been identified. In this work, an integrated metabolomic and lipidomic approach using (1)H nuclear magnetic resonance and ultra-fast LC-MS was employed to investigate the discrimination of plasma metabolic profiles between HS-free and HS lactating dairy cows. Targeted detection using LC-MS in multiple reaction monitoring mode was used to verify the reliability of the metabolites as biomarker candidates. Overall, 41 metabolites were identified as candidates for lactating dairy cows exposed to HS, among which 13 metabolites, including trimethylamine, glucose, lactate, betaine, creatine, pyruvate, acetoacetate, acetone, β-hydroxybutyrate, C16 sphinganine, lysophosphatidylcholine (18:0), phosphatidylcholine (16:0/14:0), and arachidonic acid, had high sensitivity and specificity in diagnosing HS status, and are likely to be the potential biomarkers of HS dairy cows. All of these potentially diagnostic biomarkers were involved in carbohydrate, amino acid, lipid, or gut microbiome-derived metabolism, indicating that HS affected the metabolic pathways in lactating dairy cows. Further research is warranted to evaluate these biomarkers in practical applications and to elucidate the physiological mechanisms of HS-induced metabolic disorders. Heat stress (HS) annually causes huge losses to global dairy industry, including animal performance decrease, metabolic disorder and health problem. So far, physiological mechanisms underlying HS of dairy cows still remain elusive. To our best knowledge, this is the first attempt to elucidate the HS-induced metabolic disorders of dairy cows using integrated (1)H NMR and LC-MS-based metabolic study. The results not only provided potential diagnostic biomarkers for HS lactating dairy cows, but also significantly explored the related physiological mechanisms of metabolic pathway shifts induced by HS environment. This work offers comprehensive insights into the global metabolic alterations of dairy cows exposed to HS and provides a new perspective for further study. Copyright © 2015 Elsevier B.V. All rights reserved.

Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults

PubMed Central

Maganga, Emmanuel; Smart, Luke R.; Kalluvya, Samuel; Kataraihya, Johannes B.; Saleh, Ahmed M.; Obeid, Lama; Downs, Jennifer A.; Fitzgerald, Daniel W.; Peck, Robert N.

2015-01-01

Introduction Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders. Methods In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders. Results HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%. Conclusions HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution. PMID:26287742

The Changing Face of Hypophosphatemic Disorders in the FGF-23 Era

PubMed Central

Lee, Janet Y.; Imel, Erik A.

2014-01-01

In the past decade, research in genetic disorders of hypophosphatemia has significantly expanded our understanding of phosphate metabolism. X-linked hypophosphatemia (XLH) is the most common inherited form of rickets due to renal phosphate wasting. Recent understanding of the mechanisms of disease and role of fibroblast growth factor 23 (FGF-23) in XLH and other hypophosphatemic disorders have opened new potential therapeutic avenues. We will discuss the current standard of treatment for XLH as well as promising future directions under study. PMID:23858620

Metabolic acidosis as an underlying mechanism of respiratory distress in children with severe acute asthma.

PubMed

Meert, Kathleen L; Clark, Jeff; Sarnaik, Ashok P

2007-11-01

1) To alert the clinician that increasing rate and depth of breathing during treatment of acute asthma may be a manifestation of metabolic acidosis with hyperventilation rather than worsening airway obstruction; and 2) to describe the frequency of metabolic acidosis with hyperventilation in children with severe acute asthma admitted to our pediatric intensive care unit. Retrospective medical record review. University-affiliated children's hospital. All patients admitted to the pediatric intensive care unit with a diagnosis of asthma between January 1, 2005, and December 31, 2005. None. Fifty-three patients with asthma (median age 7.8 yrs, range 0.7-17.9 yrs; 35 [66%] male; 46 [87%] black and 7 [13%] white) were admitted to the pediatric intensive care unit during the study period. Fifteen (28%) patients developed metabolic acidosis with hyperventilation (pH <7.35, Pco2 <35 torr [4.6 kPa], and base excess < or = -7 mmol/L) during their hospital course. Of these, lactic acid was assessed in four patients and was elevated in each; all had hyperglycemia (blood glucose >120 mg/dL [6.7 mmol/L]). Patients who developed metabolic acidosis with hyperventilation received asthma therapy similar to that received by patients who did not develop the disorder. Metabolic acidosis resolved contemporaneously with tapering of beta2-adrenergic agonists and administration of supportive care. All patients survived. Metabolic acidosis with hyperventilation manifesting as respiratory distress can occur in children with severe acute asthma. A pathophysiologic rationale exists for the contribution of beta2-adrenergic agents to the development of this acid-base disorder. Failure to recognize metabolic acidosis as the underlying mechanism of respiratory distress may lead to inappropriate intensification of bronchodilator therapy. Supportive care and tapering of beta2-adrenergic agents are recommended to resolve this condition.

Devastating metabolic brain disorders of newborns and young infants.

PubMed

Yoon, Hyun Jung; Kim, Ji Hye; Jeon, Tae Yeon; Yoo, So-Young; Eo, Hong

2014-01-01

Metabolic disorders of the brain that manifest in the neonatal or early infantile period are usually associated with acute and severe illness and are thus referred to as devastating metabolic disorders. Most of these disorders may be classified as organic acid disorders, amino acid metabolism disorders, primary lactic acidosis, or fatty acid oxidation disorders. Each disorder has distinctive clinical, biochemical, and radiologic features. Early diagnosis is important both for prompt treatment to prevent death or serious sequelae and for genetic counseling. However, diagnosis is often challenging because many findings overlap and may mimic those of more common neonatal conditions, such as hypoxic-ischemic encephalopathy and infection. Ultrasonography (US) may be an initial screening method for the neonatal brain, and magnetic resonance (MR) imaging is the modality of choice for evaluating metabolic brain disorders. Although nonspecific imaging findings are common in early-onset metabolic disorders, characteristic patterns of brain involvement have been described for several disorders. In addition, diffusion-weighted images may be used to characterize edema during an acute episode of encephalopathy, and MR spectroscopy depicts changes in metabolites that may help diagnose metabolic disorders and assess response to treatment. Imaging findings, including those of advanced MR imaging techniques, must be closely reviewed. If one of these rare disorders is suspected, the appropriate biochemical test or analysis of the specific gene should be performed to confirm the diagnosis. ©RSNA, 2014.

Osteochondrodysplasias

MedlinePlus

... Drugs Ear, Nose, and Throat Disorders Eye Disorders Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic ... Drugs Ear, Nose, and Throat Disorders Eye Disorders Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic ...

Osteopetroses

MedlinePlus

... Drugs Ear, Nose, and Throat Disorders Eye Disorders Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic ... Drugs Ear, Nose, and Throat Disorders Eye Disorders Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic ...

Proteomics analysis of human placenta reveals glutathione metabolism dysfunction as the underlying pathogenesis for preeclampsia.

PubMed

Jin, Xiaohan; Xu, Zhongwei; Cao, Jin; Shao, Ping; Zhou, Maobin; Qin, Zhe; Liu, Yan; Yu, Fang; Zhou, Xin; Ji, Wenjie; Cai, Wei; Ma, Yongqiang; Wang, Chengyan; Shan, Nana; Yang, Ning; Chen, Xu; Li, Yuming

2017-09-01

Hypertensive disorder in pregnancy (HDP) refers to a series of diseases that cause the hypertension during pregnancy, including HDP, preeclampsia (PE) and eclampsia. This study screens differentially expressed proteins of placenta tissues in PE cases using 2D LC-MS/MS quantitative proteomics strategy. A total of 2281 proteins are quantified, of these, 145 altering expression proteins are successfully screened between PE and control cases (p<0.05). Bioinformatics analysis suggests that these proteins are mainly involved in many biological processes, such as oxidation reduction, mitochondrion organization, and acute inflammatory response. Especially, the glutamine metabolic process related molecules, GPX1, GPX3, SMS, GGCT, GSTK1, NFκB, GSTT2, SOD1 and GCLM, are involved in the switching process from oxidized glutathione (GSSG) conversion to the reduced glutathione (GSH) by glutathione, mercapturic acid and arginine metabolism process. Results of this study revealed that glutathione metabolism disorder of placenta tissues may contribute to the occurrence of PE disease. Copyright © 2017. Published by Elsevier B.V.

Effect of a single dose of propofol and lack of dextrose administration in a child with mitochondrial disease: a case report.

PubMed

Mtaweh, Haifa; Bayır, Hülya; Kochanek, Patrick M; Bell, Michael J

2014-08-01

Propofol infusion syndrome is a recognized complication of prolonged propofol use in the pediatric population, but little is reported on other metabolic effects of propofol, especially in children with mitochondrial disorders. We report on a child with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome who received a single dose of propofol for procedural sedation. The patient's initial presentation was consistent with a mild exacerbation of her underlying disease. She received a single dose of propofol and non-dextrose-containing fluids during a magnetic resonance imaging (MRI) study to rule out stroke and progressed to develop severe acidosis, neurologic deterioration, and cardiorespiratory compromise. This is the first case report of severe metabolic disturbances after a single dose of propofol administered for procedural sedation in a patient with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome and it questions the safety of propofol and absence of dextrose infusions during an acute illness in patients with mitochondrial disorders. © The Author(s) 2013.

Leptin and the central nervous system control of glucose metabolism.

PubMed

Morton, Gregory J; Schwartz, Michael W

2011-04-01

The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders.

Leptin and the CNS Control of Glucose Metabolism

PubMed Central

Morton, Gregory J.; Schwartz, Michael W.

2012-01-01

The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system (CNS) plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders. PMID:21527729

Metabolism Disrupting Chemicals and Metabolic Disorders

PubMed Central

Heindel, Jerrold J.; Blumberg, Bruce; Cave, Mathew; Machtinger, Ronit; Mantovani, Alberto; Mendez, Michelle A.; Nadal, Angel; Palanza, Paola; Panzica, Giancarlo; Sargis, Robert; Vandenberg, Laura N.; Saal, Frederick vom

2016-01-01

The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations. PMID:27760374

Neuropsychiatric features associated with nutritional and metabolic status in a gastric bypass patient.

PubMed

Waserman, Jessica E; Hategan, Ana; Bourgeois, James A

2015-01-01

Bariatric patients may present for psychiatric evaluation due to exacerbation of preexisting psychiatric disorders, new onset psychiatric disorders and/or neuropsychiatric complications associated with abnormal nutritional and metabolic states following the surgical procedure. These neuropsychiatric complications can be insidious, and clinical manifestations may vary, possibly due to the individual central nervous system (CNS) vulnerability to nutritional decline. Lack of awareness of these complications and their symptoms can result in delays in diagnosis and treatment. Identifying and correcting underlying pathophysiologic processes that lead to such neuropsychiatric syndromes can be challenging. We report a case of a patient who developed a protracted course of mood and cognitive disorder after gastric bypass surgery, which illustrates some of the complexities encountered in diagnosing and managing these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Insulin resistance, the metabolic syndrome, diabetes, and cardiovascular disease risk in women with PCOS.

PubMed

Teede, H J; Hutchison, S; Zoungas, S; Meyer, C

2006-08-01

Polycystic ovary syndrome is the most common endocrinopathy of reproductive aged women affecting 6-10% of the population. Traditionally considered a reproductive disorder manifesting as chronic anovulation, infertility, and hyperandrogenism, management has primarily focused on short-term reproductive outcomes. Recently, however, significant metabolic aspects in conjunction with longer-term health sequealae of PCOS have been recognized. The metabolic features are primarily related to underlying insulin resistance (IR), which is now understood to play an important role in both the pathogenesis and long-term sequelae of PCOS.

Congestive Hepatomegaly

MedlinePlus

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Cutis Laxa

MedlinePlus

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Bacterial Tracheitis

MedlinePlus

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Inherited metabolic disorders presenting as acute liver failure in newborns and young children: King's College Hospital experience.

PubMed

Hegarty, Robert; Hadzic, Nedim; Gissen, Paul; Dhawan, Anil

2015-10-01

Acute liver failure (ALF) in children is a rare condition that is often fatal without liver transplantation. The diagnostic work-up is complex, and the etiology is unidentified in up to half of patients, making decisions like therapeutic transplantation extremely difficult. We collected clinical, laboratory, and outcome data on all patients under 5 years of age who were admitted between January 2001 and December 2011 to King's College Hospital with ALF secondary to an inherited metabolic disease (IMD), a common cause of pediatric acute liver failure. Thirty-six of 127 children with ALF had a metabolic etiology: galactosemia (17); mitochondrial respiratory chain disorder (MRCD, 7); ornithine transcarbamylase (OTC) deficiency (4); tyrosinemia type 1 (4); Niemann-Pick disease type C (NPC, 3); and congenital disorder of glycosylation type 1b (1). Seven children died: MRCD (4) and NPC (3). Four children were transplanted: OTC deficiency (1) and MRCD (3). Fifteen of 25 children followed up showed evidence of developmental delay. IMD is the most common group of disorders in this age group; indeterminate cases may yet include undiagnosed metabolic disorders; the overall survival rate is good but largely depends on diagnosis, while developmental outcome of the surviving patients is less favorable. • Up to half of children with ALF may be undiagnosed. • IMD is a common cause of pediatric acute liver failure. What is New: • Initial diagnostic clues may be gathered from the child's age and laboratory parameters. • Survival of children with IMD-related ALF is good, but developmental outcome is less favorable. • In the future, novel sequencing methods will aid in the diagnosis of disorders in which therapeutic decisions depend upon.

Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review.

PubMed

Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

2011-09-01

Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.

Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring.

PubMed

Reynolds, Clare M; Segovia, Stephanie A; Vickers, Mark H

2017-01-01

Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut-brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.

Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders

PubMed Central

Cho, Min-Chul; Lee, Kyoung; Paik, Sang-Gi; Yoon, Do-Young

2008-01-01

Overweight and obesity lead to an increased risk for metabolic disorders such as impaired glucose regulation/insulin resistance, dyslipidemia, and hypertension. Several molecular drug targets with potential to prevent or treat metabolic disorders have been revealed. Interestingly, the activation of peroxisome proliferator-activated receptor (PPAR), which belongs to the nuclear receptor superfamily, has many beneficial clinical effects. PPAR directly modulates gene expression by binding to a specific ligand. All PPAR subtypes (α, γ, and σ) are involved in glucose metabolism, lipid metabolism, and energy balance. PPAR agonists play an important role in therapeutic aspects of metabolic disorders. However, undesired effects of the existing PPAR agonists have been reported. A great deal of recent research has focused on the discovery of new PPAR modulators with more beneficial effects and more safety without producing undesired side effects. Herein, we briefly review the roles of PPAR in metabolic disorders, the effects of PPAR modulators in metabolic disorders, and the technologies with which to discover new PPAR modulators. PMID:18566691

[Inherited metabolic disorders in pediatric emergency services].

PubMed

Molina Gutiérrez, M A; López López, R; Morais López, A; Bueno Barriocanal, M; Martínez Ojinaga Nodal, E; Alcolea Sánchez, A M; García García, S

2015-06-01

Advances in the early diagnosis and treatment have led to improved survival, and a better quality of life for patients with inherited metabolic disorders (IMD). They can go to the Pediatric Emergency Services (PES) for reasons unrelated to their disease. The purpose of this study was to review the characteristics of visitors to the PES of these patients in a tertiary hospital. A retrospective observational study was conducted on all visits from patients with IMD to the PES of Hospital Infantil La Paz over the years 2011 and 2012. IMD type, complaint, duration of symptoms, need for hospitalization, and presence of metabolic decompensation was recorded. A total of 107 visits were analyzed, with the most frequent reason being for consultation of respiratory processes (30.8%). When the consultation was for vomiting, patients with protein-related disorders were those who delayed less in going to PES. One third of visitors were admitted, half of them due to metabolic decompensation of the underlying pathology. Patients with IMD came to PES for many different reasons, which in some cases were the cause or consequence of an acute metabolic decompensation that led to hospitalization. Being diseases with low prevalence, it would be useful to have diagnostic and therapeutic protocols in order to provide optimal care. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Anemia in the Newborn

MedlinePlus

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Birth Injury in Newborns

MedlinePlus

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Measure Liver Fat Content After ISIS 301012 (Mipomersen) Administration

ClinicalTrials.gov

2016-09-09

Lipid Metabolism, Inborn Errors; Hyperlipidemias; Metabolic Diseases; Hypolipoproteinemia; Hypolipoproteinemias; Hypobetalipoproteinemias; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Congenital Abnormalities; Metabolic Disorder; Hypercholesterolemia; Dyslipidemias; Lipid Metabolism Disorders

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases.

PubMed

Vivante, Asaf; Ityel, Hadas; Pode-Shakked, Ben; Chen, Jing; Shril, Shirlee; van der Ven, Amelie T; Mann, Nina; Schmidt, Johanna Magdalena; Segel, Reeval; Aran, Adi; Zeharia, Avraham; Staretz-Chacham, Orna; Bar-Yosef, Omer; Raas-Rothschild, Annick; Landau, Yuval E; Lifton, Richard P; Anikster, Yair; Hildebrandt, Friedhelm

2017-12-01

Rhabdomyolysis is a clinical emergency that may cause acute kidney injury (AKI). It can be acquired or due to monogenic mutations. Around 60 different rare monogenic forms of rhabdomyolysis have been reported to date. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to nonspecific presentation, the high number of causative genes, and current lack of data on the prevalence of monogenic forms. We employed whole exome sequencing (WES) to reveal the percentage of rhabdomyolysis cases explained by single-gene (monogenic) mutations in one of 58 candidate genes. We investigated a cohort of 21 unrelated families with rhabdomyolysis, in whom no underlying etiology had been previously established. Using WES, we identified causative mutations in candidate genes in nine of the 21 families (43%). We detected disease-causing mutations in eight of 58 candidate genes, grouped into the following categories: (1) disorders of fatty acid metabolism (CPT2), (2) disorders of glycogen metabolism (PFKM and PGAM2), (3) disorders of abnormal skeletal muscle relaxation and contraction (CACNA1S, MYH3, RYR1 and SCN4A), and (4) disorders of purine metabolism (AHCY). Our findings demonstrate a very high detection rate for monogenic etiologies using WES and reveal broad genetic heterogeneity for rhabdomyolysis. These results highlight the importance of molecular genetic diagnostics for establishing an etiologic diagnosis. Because these patients are at risk for recurrent episodes of rhabdomyolysis and subsequent risk for AKI, WES allows adequate prophylaxis and treatment for these patients and their family members and enables a personalized medicine approach.

Metabolic dysfunction in obstructive sleep apnea: A critical examination of underlying mechanisms

PubMed Central

MESARWI, Omar A.; SHARMA, Ellora V.; JUN, Jonathan C.; POLOTSKY, Vsevolod Y.

2015-01-01

It has recently become clear that obstructive sleep apnea (OSA) is an independent risk factor for the development of metabolic syndrome, a disorder of defective energy storage and use. Several mechanisms have been proposed to explain this finding, drawing upon the characteristics that define OSA. In particular, intermittent hypoxia, sleep fragmentation, elevated sympathetic tone, and oxidative stress – all consequences of OSA – have been implicated in the progression of poor metabolic outcomes in OSA. In this review we examine the evidence to support each of these disease manifestations of OSA as a unique risk for metabolic dysfunction. Tissue hypoxia and sleep fragmentation are each directly connected to insulin resistance and hypertension, and each of these also may increase sympathetic tone, resulting in defective glucose homeostasis, excessive lipolysis, and elevated blood pressure. Oxidative stress further worsens insulin resistance and in turn, metabolic dysfunction also increases oxidative stress. However, despite many studies linking each of these individual components of OSA to the development of metabolic syndrome, there are very few reports that actually provide a coherent narrative about the mechanism underlying metabolic dysfunction in OSA. PMID:26412981

Large for Gestational Age (LGA)

MedlinePlus

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Multi-Disciplinary Diagnosis.

ERIC Educational Resources Information Center

Schiffman, Gilbert B.

The diagnosis of severely retarded pupils as an interdisciplinary concern is discussed. Descriptions of the severe reading disability syndrome given by various disciplines are presented under the following headings: Neurological Factors--minimal brain damage, lateral dominance; Physical Factors--endocrine and metabolic disorders, optical and…

Genetic and pharmacological correction of aberrant dopamine synthesis using patient iPSCs with BH4 metabolism disorders.

PubMed

Ishikawa, Taizo; Imamura, Keiko; Kondo, Takayuki; Koshiba, Yasushi; Hara, Satoshi; Ichinose, Hiroshi; Furujo, Mahoko; Kinoshita, Masako; Oeda, Tomoko; Takahashi, Jun; Takahashi, Ryosuke; Inoue, Haruhisa

2016-12-01

Dopamine (DA) is a neurotransmitter in the brain, playing a central role in several disease conditions, including tetrahydrobiopterin (BH4) metabolism disorders and Parkinson's disease (PD). BH4 metabolism disorders present a variety of clinical manifestations including motor disturbance via altered DA metabolism, since BH4 is a cofactor for tyrosine hydroxylase (TH), a rate-limiting enzyme for DA synthesis. Genetically, BH4 metabolism disorders are, in an autosomal recessive pattern, caused by a variant in genes encoding enzymes for BH4 synthesis or recycling, including 6-pyruvoyltetrahydropterin synthase (PTPS) or dihydropteridine reductase (DHPR), respectively. Although BH4 metabolism disorders and its metabolisms have been studied, it is unclear how gene variants cause aberrant DA synthesis in patient neurons. Here, we generated induced pluripotent stem cells (iPSCs) from BH4 metabolism disorder patients with PTPS or DHPR variants, corrected the gene variant in the iPSCs using the CRISPR/Cas9 system, and differentiated the BH4 metabolism disorder patient- and isogenic control iPSCs into midbrain DA neurons. We found that by the gene correction, the BH4 amount, TH protein level and extracellular DA level were restored in DA neuronal culture using PTPS deficiency iPSCs. Furthermore, the pharmacological correction by BH4 precursor sepiapterin treatment also improved the phenotypes of PTPS deficiency. These results suggest that patient iPSCs with BH4 metabolism disorders provide an opportunity for screening substances for treating aberrant DA synthesis-related disorders. © The Author 2016. Published by Oxford University Press.

Current status of iron metabolism: Clinical and therapeutic implications.

PubMed

Conde Diez, Susana; de Las Cuevas Allende, Ricardo; Conde García, Eulogio

2017-03-03

Hepcidin is the main regulator of iron metabolism and a pathogenic factor in iron disorders. Hepcidin deficiency causes iron overload, whereas hepcidin excess causes or contributes to the development of iron-restricted anaemia in chronic inflammatory diseases. We know the mechanisms involved in the synthesis of hepcidin and, under physiological conditions, there is a balance between activating signals and inhibitory signals that regulate its synthesis. The former include those related to plasmatic iron level and also those related to chronic inflammatory diseases. The most important inhibitory signals are related to active erythropoiesis and to matriptase-2. Knowing how hepcidin is synthesised has helped design new pharmacological treatments whose main target is the hepcidin. In the near future, there will be effective treatments aimed at correcting the defect of many of these iron metabolism disorders. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency--diagnostic difficulties and own experience in multidisciplinary management.

PubMed

Stępień, Karolina M; Roberts, Mark; Hendriksz, Christian J

2015-01-01

A 19-year old female patient presented with a two-year history of muscle pain and weakness before she was admitted to an acute medical ward with rhabdomyolysis (creatine kinase of 83,344 IU/L) and normal renal function tests. Following admission she was under the care of the rheumatology and neurology teams, which investigated her thoroughly. As part of the belt-and-braces approach, both teams contacted the specialist Adult Inherited Metabolic Disorders team for advice, instigating definitive diagnostic investigations. An accurate diagnosis was required, as an inherited metabolic disorders can present in adult patients as a milder form of the disease. Very-long-chain Acyl-CoA dehydrogenase (VLCAD) deficiency should always be considered as a differential diagnosis of myopathy-related symptoms. Hence, the liaison between neurologists, rheumatologists and metabolic physicians is essential in early diagnosis and the management of patients with conditions causing myopathy.

Neurological and psychiatric disorders in thyroid dysfunctions. The role of nuclear medicine: SPECT and PET imaging.

PubMed

Lass, P; Slawek, J; Derejko, M; Rubello, D

2008-06-01

Thyroid dysfunctions may be accompanied by numerous neurological and psychiatric disorders. The most known is cognitive impairment and depression in hypothyroid patients, as well as an increased risk of cerebrovascular accidents. A separate, although a rare entity, is Hashimoto's encephalopathy. In hyperthyroidism there is an increased incidence of psychiatric disorders, including apathetic hyperthyroidism and hyperthyroid dementia. Functional imaging of cerebral blood flow and metabolism helped establish both global and/or regional decrease of both cerebral blood flow and metabolism in hypothyroidism, particularly in regions mediating attention, motor speed and visuospatial processing. Hypothyroid dementia may be mediated by neurocircuitry different from that in major depression. Less is known on flow/metabolism changes in hyperthyroidism. Global blood flow may be slightly increased, with regional deficits of blood flow, particular in hyperthyroid dementia. As presented above radionuclide functional imaging showed some metabolic patterns in thyroid dysfunctions, but still many issues remain unresolved. In particular little is known about the underlying pathology of cognitive impairment and depression in hypothyroidism, which may differ from ones in euthyroid patients. Also little is known about the reversibility of changes in cerebral blood flow following thyroid replacement therapy. In hyperthyroid patients functional imaging might contribute to elucidate the background of apathetic hyperthyroidism and potential different background of psychiatric complications.

Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia

ClinicalTrials.gov

2016-08-01

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

Life-stage and organ specific changes in mitochondrial bioenergetics in Brown Norway Rats

EPA Science Inventory

Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence and age-related neurodegenerative and metabolic disorders. However, mitochondrial bioenergetic parameters have not been systematically evaluated under identical ...

Mitochondrial bioenergetics in young, adult, middle-age and senescent brown Norway rats

EPA Science Inventory

Mitochondria are central regulators of energy homeostasis and may play a pivotal role in mechanisms of cellular senescence and age-related neurodegenerative and metabolic disorders. However, mitochondrial bioenergetic parameters have not been systematically evaluated under identi...

A review on hyperthyroidism: thyrotoxicosis under surveillance.

PubMed

Mansourian, Azad Reza

2010-11-15

Thyrotoxicosis exhibit collective clinical manifestation, caused by excessive serum thyroid hormones particularity thyroxin. The clinical signs and symptoms included general alteration of metabolic process leading to weight loss fatigue and weakness and some specific disorders such as cardiovascular, neuromuscular reproductive gastrointestinal dermatological and bone disorders. The diagnosis of thyrotoxicosis relay on the thyroid function test carried out by the laboratory serum measurement of thyroxin, triiodothyronine and thyroid stimulating hormones accompanied by other para-medical examinations suggested by clinicians and endociologicst. In thyrotoxicosis serum level of thyroid hormones and thyroxin in particular elevated accompanied by pituitary thyroid stimulating hormone suppression reaching to undetectable level in sever thyrotoxicosis. Among the most common cause of thyrotoxicosis are, thyroid autoimmunity diseases thyroid toxic, adenoma toxic nodular and multinodular hyperthyroidism. The main aim behind this review is to explore the clinical manifestation, the causative factors, diagnosis, metabolic disorder occur due to thyrotoxicosis.

Metabolic syndrome in a French cohort of patients with bipolar disorder: results from the FACE-BD cohort.

PubMed

Godin, Ophélia; Etain, Bruno; Henry, Chantal; Bougerol, Thierry; Courtet, Philippe; Mayliss, Leroux; Passerieux, Christine; Azorin, Jean-Michel; Kahn, Jean-Pierre; Gard, Sebastien; Costagliola, Dominique; Leboyer, Marion

2014-10-01

The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its components in a cohort of French patients with bipolar disorder; determine correlations with sociodemographic, clinical, and treatment-related factors; and investigate the gap between optimal care and effective care of the treated patients. 654 bipolar disorder patients from the FACE-BD cohort were included from 2009 to 2012. Sociodemographic and clinical characteristics, lifestyle information, and data on antipsychotic treatment and comorbidities were collected, and a blood sample was drawn. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis of bipolar disorder. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. 18.5% of individuals with bipolar disorder met criteria for MetS. Two-thirds of bipolar disorder patients did not receive adequate treatment for MetS components. Multivariate analysis showed that risk of MetS in men was nearly twice that in women (OR = 1.9; 95% CI, 1.0-3.8), and older patients had a 3.5 times higher risk (95% CI, 1.5-7.8) of developing MetS than patients under the age of 35 years. Moreover, patients receiving antipsychotic treatment had a 2.3 times increased risk (95% CI, 1.2-3.5) of having MetS, independent of other potential confounders. The prevalence of MetS is high in bipolar disorder patients, and there was considerable undertreatment of the components of MetS in this population. The prevention and treatment of cardiovascular diseases in these patients should be assessed systematically. The findings highlight the need for integrated care, with more interaction and coordination between psychiatrists and primary care providers. © Copyright 2014 Physicians Postgraduate Press, Inc.

Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia

ClinicalTrials.gov

2016-08-01

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

Chilling-related cell damage of apple (Malus × domestica Borkh.) fruit cortical tissue impacts antioxidant, lipid and phenolic metabolism.

PubMed

Leisso, Rachel S; Buchanan, David A; Lee, Jinwook; Mattheis, James P; Sater, Chris; Hanrahan, Ines; Watkins, Christopher B; Gapper, Nigel; Johnston, Jason W; Schaffer, Robert J; Hertog, Maarten L A T M; Nicolaï, Bart M; Rudell, David R

2015-02-01

'Soggy breakdown' (SB) is an internal flesh disorder of 'Honeycrisp' apple (Malus × domestica Borkh.) fruit that occurs during low temperature storage. The disorder is a chilling injury (CI) in which visible symptoms typically appear after several weeks of storage, but information about the underlying metabolism associated with its induction and development is lacking. The metabolic profile of flesh tissue from wholly healthy fruit and brown and healthy tissues from fruit with SB was characterized using gas chromatography-mass spectrometry (GC-MS) and liquid chromatograph-mass spectrometry (LC-MS). Partial least squares discriminant analysis (PLS-DA) and correlation networks revealed correlation among ester volatile compounds by composition and differences in phytosterol, phenolic and putative triacylglycerides (TAGs) metabolism among the tissues. anova-simultaneous component analysis (ASCA) was used to test the significance of metabolic changes linked with tissue health status. ASCA-significant components included antioxidant compounds, TAGs, and phytosterol conjugates. Relative to entirely healthy tissues, elevated metabolite levels in symptomatic tissue included γ-amino butyric acid, glycerol, sitosteryl (6'-O-palmitoyl) β-d-glucoside and sitosteryl (6'-O-stearate) β-d-glucoside, and TAGs containing combinations of 16:0, 18:3, 18:2 and 18:1 fatty acids. Reduced metabolite levels in SB tissue included 5-caffeoyl quinate, β-carotene, catechin, epicatechin, α-tocopherol, violaxanthin and sitosteryl β-d glucoside. Pathway analysis indicated aspects of primary metabolism differed according to tissue condition, although differences in metabolites involved were more subtle than those of some secondary metabolites. The results implicate oxidative stress and membrane disruption processes in SB development and constitute a diagnostic metabolic profile for the disorder. © 2014 Scandinavian Plant Physiology Society.

Metabolic decoupling in daily life in patients with panic disorder and agoraphobia.

PubMed

Pfaltz, Monique C; Kolodyazhniy, Vitaliy; Blechert, Jens; Margraf, Jürgen; Grossman, Paul; Wilhelm, Frank H

2015-09-01

Various studies have assessed autonomic and respiratory underpinnings of panic attacks, yet the psychophysiological functioning of panic disorder (PD) patients has rarely been examined under naturalistic conditions at times when acute attacks were not reported. We hypothesized that emotional activation in daily life causes physiologically demonstrable deviations from efficient metabolic regulation in PD patients. Metabolic coupling was estimated as within-individual correlations between heart rate (HR) and indices of metabolic activity, i.e., physical activity (measured by 3-axial accelerometry, Acc), and minute ventilation (Vm, measured by calibrated inductive plethysmography, as proxy for oxygen consumption). A total of 565 daytime hours were recorded in 19 PD patients and 20 healthy controls (HC). Pairwise cross-correlations of minute-by-minute averages of these metabolic indices were calculated for each participant and then correlated with several indices of self-reported anxiety. Ambulatory HR was elevated in PD (p = .05, d = 0.67). Patients showed reduced HR-Acc (p < .006, d = 0.97) and HR-Vm coupling (p < .009, d = 0.91). Combining Vm and Acc to predict HR showed the strongest group separation (p < .002, d = 1.07). Discriminant analyses, based on the combination of Vm and Acc to predict HR, classified 77% of all participants correctly. In PD, HR-Acc coupling was inversely related to trait anxiety sensitivity, as well as tonic and phasic daytime anxiety. The novel method that was used demonstrates that anxiety in PD may reduce efficient long-term metabolic coupling. Metabolic decoupling may serve as physiological characteristic of PD and might aid diagnostics for PD and other anxiety disorders. This measure deserves further study in research on health consequences of anxiety and psychosocial stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unexpected metabolic disorders induced by endocrine disruptors in Xenopus tropicalis provide new lead for understanding amphibian decline.

PubMed

Regnault, Christophe; Usal, Marie; Veyrenc, Sylvie; Couturier, Karine; Batandier, Cécile; Bulteau, Anne-Laure; Lejon, David; Sapin, Alexandre; Combourieu, Bruno; Chetiveaux, Maud; Le May, Cédric; Lafond, Thomas; Raveton, Muriel; Reynaud, Stéphane

2018-05-08

Despite numerous studies suggesting that amphibians are highly sensitive to endocrine disruptors (EDs), both their role in the decline of populations and the underlying mechanisms remain unclear. This study showed that frogs exposed throughout their life cycle to ED concentrations low enough to be considered safe for drinking water, developed a prediabetes phenotype and, more commonly, a metabolic syndrome. Female Xenopus tropicalis exposed from tadpole stage to benzo( a )pyrene or triclosan at concentrations of 50 ng⋅L -1 displayed glucose intolerance syndrome, liver steatosis, liver mitochondrial dysfunction, liver transcriptomic signature, and pancreatic insulin hypersecretion, all typical of a prediabetes state. This metabolic syndrome led to progeny whose metamorphosis was delayed and occurred while the individuals were both smaller and lighter, all factors that have been linked to reduced adult recruitment and likelihood of reproduction. We found that F 1 animals did indeed have reduced reproductive success, demonstrating a lower fitness in ED-exposed Xenopus Moreover, after 1 year of depuration, Xenopus that had been exposed to benzo( a )pyrene still displayed hepatic disorders and a marked insulin secretory defect resulting in glucose intolerance. Our results demonstrate that amphibians are highly sensitive to EDs at concentrations well below the thresholds reported to induce stress in other vertebrates. This study introduces EDs as a possible key contributing factor to amphibian population decline through metabolism disruption. Overall, our results show that EDs cause metabolic disorders, which is in agreement with epidemiological studies suggesting that environmental EDs might be one of the principal causes of metabolic disease in humans.

Psoriasis and metabolic syndrome.

PubMed

Sales, Rita; Torres, Tiago

2014-01-01

Psoriasis is a chronic, systemic inflammatory disease associated with several cardiometabolic comorbidities, such as obesity, insulin resistance, dyslipidemia, and hypertension, and with clinically significant increased risk of cardiovascular disease and cardiovascular mortality. These comorbidities are components of the metabolic syndrome. Multiple epidemiologic studies have revealed a high prevalence of metabolic syndrome in patients with psoriasis compared with other skin diseases. Genetic susceptibility and overlapping inflammatory pathways may be potential biologic links underlying this association. Understanding the interrelationship between these conditions is important for the management of psoriasis and its associated comorbidities. This review will focus on the range of these comorbidities, with emphasis on the metabolic syndrome, aiming to encourage physicians to screen patients with psoriasis for cardiometabolic disorders and risk factors.

Pharmacogenetics of Vascular Risk Factors in Alzheimer’s Disease

PubMed Central

Cacabelos, Ramón; Meyyazhagan, Arun; Carril, Juan C.; Cacabelos, Pablo; Teijido, Óscar

2018-01-01

Alzheimer’s disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products. Only 20% of the Caucasian population are extensive metabolizers for tetragenic haplotypes integrating CYP2D6-CYP2C19-CYP2C9-CYP3A4/5 variants. Patients harboring CYP-related poor (PM) and/or ultra-rapid (UM) geno-phenotypes display more irregular profiles in drug metabolism than extensive (EM) or intermediate (IM) metabolizers. Among 111 pentagenic (APOE-APOB-APOC3-CETP-LPL) haplotypes associated with lipid metabolism, carriers of the H26 haplotype (23-TT-CG-AG-CC) exhibit the lowest cholesterol levels, and patients with the H104 haplotype (44-CC-CC-AA-CC) are severely hypercholesterolemic. Furthermore, APOE, NOS3, ACE, AGT, and CYP variants influence the therapeutic response to hypotensive drugs in AD patients with hypertension. Consequently, the implementation of pharmacogenetic procedures may optimize therapeutics in AD patients under polypharmacy regimes for the treatment of concomitant vascular disorders. PMID:29301387

Pharmacogenetics of Vascular Risk Factors in Alzheimer's Disease.

PubMed

Cacabelos, Ramón; Meyyazhagan, Arun; Carril, Juan C; Cacabelos, Pablo; Teijido, Óscar

2018-01-03

Alzheimer's disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products. Only 20% of the Caucasian population are extensive metabolizers for tetragenic haplotypes integrating CYP2D6-CYP2C19-CYP2C9-CYP3A4/5 variants. Patients harboring CYP-related poor (PM) and/or ultra-rapid (UM) geno-phenotypes display more irregular profiles in drug metabolism than extensive (EM) or intermediate (IM) metabolizers. Among 111 pentagenic ( APOE-APOB-APOC3-CETP-LPL ) haplotypes associated with lipid metabolism, carriers of the H26 haplotype (23-TT-CG-AG-CC) exhibit the lowest cholesterol levels, and patients with the H104 haplotype (44-CC-CC-AA-CC) are severely hypercholesterolemic. Furthermore, APOE , NOS3 , ACE , AGT , and CYP variants influence the therapeutic response to hypotensive drugs in AD patients with hypertension. Consequently, the implementation of pharmacogenetic procedures may optimize therapeutics in AD patients under polypharmacy regimes for the treatment of concomitant vascular disorders.

Genetic disorders of thyroid metabolism and brain development

PubMed Central

Kurian, Manju A; Jungbluth, Heinz

2014-01-01

Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

Association between the abdominal obesity anthropometric indicators and metabolic disorders in a Chinese population.

PubMed

Dong, J; Ni, Y-Q; Chu, X; Liu, Y-Q; Liu, G-X; Zhao, J; Yang, Y-B; Yan, Y-X

2016-02-01

Obesity has become a major health problem in contemporary society and it is closely related to many chronic diseases, so it is an important issue for measuring adiposity accurately and predicting its future. Prevention and treatment of overweight and obesity has become one of the key prevention and treatment of metabolic disorders. In this study, we compared the ability of the four anthropometric indicators (body mass index, waist circumstance, waist-height ratio, waist-to-hip ratio) to identify metabolic disorders (hypertension, hyperlipidaemia, hyperglycemia and hyperuricemia) by receiver operating characteristic (ROC) curve analyses and to provide evidence for clinical practice. In this large scale cross-sectional study, 13,275 Han adults (including 7595 males and 5680 females) received physical examination between January, 2009 and January, 2010 in Xuanwu Hospital of Capital Medical University were investigated by the means of questionnaire, Meanwhile, the physical examination and serological results were recorded. A package known as Statistical Package for Social Scientist (SPSS) was employed to analyse the responses while t-test, one-way analysis of variance (ANOVA), ROC analysis and chi-square statistical methods were used to test the hypotheses. WC, WHtR, WHR and BMI were all significantly (P < 0.001) correlated with all metabolic risk factors regardless of gender. And the area under the curve (AUC) of WHtR was significantly greater than that of WC, BMI or WHR in the prediction of hypertension, hyperlipidaemia, hyperglycemia and hyperuricemia. Our data show that WHtR was the best predictor of various metabolic disorders. The diagnostic value in descending order was WHtR > WHR > WC > BMI. Therefore we recommend WHtR in assessment of obese patients, in order to better assess the risks of their metabolic diseases. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

[Obesity as pathology of adipocytes: number of cells, volume of arterial bloodstream,local pools of circulation in vivo, natriuretic peptides and arterial hypertension].

PubMed

Titov, V N; Dmitriev, V A

2015-03-01

The non-specific systemic biological reaction of arterial pressure from the level of organism. vasomotor center and proximal section of arterial bloodstream is appealed to compensate disorders of metabolism and microcirculation in distal section of arteries. This phenomenon occurs in several cases. The primarily local disorders of metabolism at autocrine level, physiological (aphysiological) death of cells, "littering" of intercellular medium become the cause of disorder of microcirculation in paracrin cenosises and deteriorate realization of biological functions of homeostasis, trophology, endoecology and adaptation. The local compensation of affected perfusion in paracrin cenosises at the expense of function of peripheral peristaltic pumps, redistribution of local bloodflow in biological reaction of endothelium-depended vaso-dilation has no possibility to eliminate disorders in realization of biological functions. The systemic increase of arterial pressure under absence of specific symptoms of symptomatic arterial hypertension is a test to detect disorder of biological functions of homeostasis, trophology, biological function of endoecology and adaptation. Allforms of arterial hypertension develop by common algorithm independently from causes of disorders of blood flow, microcirculation in distal section of arteries. The non-specific systemic compensation ofdisorders of metabolism from level of organism, in proximal section of arterial bloodstream always is the same one and results in aphysiological alterations in organs-targets. To comprehend etiological characteristics of common pathogenesis of arterial hypertension is possible in case of application of such technically complicated and still unclear in differential diagnostic of deranged functions modes of metabolomics.

Commentary: Potential Neurobiologic Mechanisms through Which Metabolic Disorders Could Relate to Autism.

ERIC Educational Resources Information Center

Johnston, Michael V.

2000-01-01

To illustrate the possible relationships between metabolic disorders and autism, this commentary reviews findings from studies on the characteristics of individuals with Rett syndrome that indicate the genetic mechanism of transcriptional dysregulation can produce pathologic phenotypes which resemble metabolic disorders that stunt axonodendritic…

Ophthalmologic Findings in Patients with Neuro-metabolic Disorders.

PubMed

Jafari, Narjes; Golnik, Karl; Shahriari, Mansoor; Karimzadeh, Parvaneh; Jabbehdari, Sayena

2018-01-01

We aimed to present the ophthalmic manifestations of neuro-metabolic disorders. Patients who were diagnosed with neuro-metabolic disorders in the Neurology Department of Mofid Pediatric Hospital in Tehran, Iran, between 2004 and 2014 were included in this study. Disorders were confirmed using clinical findings, neuroimaging, laboratory data, and genomic analyses. All enrolled patients were assessed for ophthalmological abnormalities. A total of 213 patients with 34 different neuro-metabolic disorders were included. Ophthalmological abnormalities were observed in 33.5% of patients. Abnormal findings in the anterior segment included Kayser-Fleischer rings, congenital or secondary cataracts, and lens dislocation into the anterior chamber. Posterior segment (i.e., retina, vitreous body, and optic nerve) evaluation revealed retinitis pigmentosa, cherry-red spots, and optic atrophy. In addition, strabismus, nystagmus, and lack of fixation were noted during external examination. Ophthalmological examination and assessment is essential in patients that may exhibit neuro-metabolic disorders.

Full penetrance of Morgagni-Stewart-Morel syndrome in a 75-year-old woman: case report and review of the literature.

PubMed

Attanasio, Francesca; Granziera, Serena; Giantin, Valter; Manzato, Enzo

2013-02-01

Morgagni-Stewart-Morel syndrome is defined as the presence of hyperostosis frontalis interna, variably associated with metabolic, endocrine, and neuropsychiatric disorders. The possible cause-effect relationship of these associations remains uncertain. A 75-year-old woman presented with severe frontal headache and a history of psychotic disorders. On instrumental examination she was found to have extensive frontal hyperostosis and cortical atrophy. These findings, associated to the metabolic and neuropsychiatric pattern of the patient, are consistent with a high penetrance of Morgagni-Stewart-Morel syndrome. In this clinical case seminar, we summarize the current understanding of the association between hyperostosis frontalis interna and Morgagni-Stewart-Morel, based on a MEDLINE search (case reports, original articles, and reviews published between 1928 and 2011) on this topic. Possible pathophysiological mechanisms underlying both the headache and the hyperostosis frontalis interna are discussed. A case of full penetrance of Morgagni-Stewart-Morel syndrome is reported, presenting many of the clinical features described in the literature. Metabolic and endocrine dysfunctions should be interpreted not only as isolated components of the syndrome, but also as the reason behind its pathogenesis. Endocrine or nutritional disorders may have led to an altered bone metabolism with frontal bone apposition. On the other hand, the severity of our patient's neurological and psychiatric symptoms correlates well with the severity of her hyperostosis frontalis interna and the cortical atrophy.

An update on the use of benzoate, phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease

PubMed Central

de las Heras, Javier; Aldámiz-Echevarría, Luis; Martínez-Chantar, María-Luz; Delgado, Teresa C.

2017-01-01

Introduction Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal. Areas Covered We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease. Expert Opinion For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine metabolism to the progression and resolution of liver disease, we propose that ammonia-scavenging drugs might also be used to non-invasively probe liver glutamine metabolism in vivo. Finally, novel derivatives of classical ammonia-scavenging drugs with fewer and less severe adverse effects are currently being developed and used in clinical trials for the treatment of acute liver failure and cirrhosis. PMID:27860485

An update on the use of benzoate, phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease.

PubMed

De Las Heras, Javier; Aldámiz-Echevarría, Luis; Martínez-Chantar, María-Luz; Delgado, Teresa C

2017-04-01

Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal. Areas covered: We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease. Expert opinion: For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine metabolism to the progression and resolution of liver disease, we propose that ammonia-scavenging drugs might also be used to non-invasively probe liver glutamine metabolism in vivo. Finally, novel derivatives of classical ammonia-scavenging drugs with fewer and less severe adverse effects are currently being developed and used in clinical trials for the treatment of acute liver failure and cirrhosis.

An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

ClinicalTrials.gov

2016-08-01

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

PubMed

Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

2016-01-01

The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

EPA Science Inventory

This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

Sleep and Eating Disorders.

PubMed

Allison, Kelly C; Spaeth, Andrea; Hopkins, Christina M

2016-10-01

Insomnia is related to an increased risk of eating disorders, while eating disorders are related to more disrupted sleep. Insomnia is also linked to poorer treatment outcomes for eating disorders. However, over the last decade, studies examining sleep and eating disorders have relied on surveys, with no objective measures of sleep for anorexia nervosa or bulimia nervosa, and only actigraphy data for binge eating disorder. Sleep disturbance is better defined for night eating syndrome, where sleep efficiency is reduced and melatonin release is delayed. Studies that include objectively measured sleep and metabolic parameters combined with psychiatric comorbidity data would help identify under what circumstances eating disorders and sleep disturbance produce an additive effect for symptom severity and for whom poor sleep would increase risk for an eating disorder. Cognitive behavior therapy for insomnia may be a helpful addition to treatment of those with both eating disorder and insomnia.

MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

PubMed

Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

2012-06-01

Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

Monitoring ATP dynamics in electrically active white matter tracts

PubMed Central

Trevisiol, Andrea; Saab, Aiman S; Winkler, Ulrike; Marx, Grit; Imamura, Hiromi; Möbius, Wiebke; Kusch, Kathrin; Nave, Klaus-Armin; Hirrlinger, Johannes

2017-01-01

In several neurodegenerative diseases and myelin disorders, the degeneration profiles of myelinated axons are compatible with underlying energy deficits. However, it is presently impossible to measure selectively axonal ATP levels in the electrically active nervous system. We combined transgenic expression of an ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological recordings of acutely isolated optic nerves. This allowed us to monitor dynamic changes and activity-dependent axonal ATP homeostasis at the cellular level and in real time. We find that changes in ATP levels correlate well with compound action potentials. However, this correlation is disrupted when metabolism of lactate is inhibited, suggesting that axonal glycolysis products are not sufficient to maintain mitochondrial energy metabolism of electrically active axons. The combined monitoring of cellular ATP and electrical activity is a novel tool to study neuronal and glial energy metabolism in normal physiology and in models of neurodegenerative disorders. DOI: http://dx.doi.org/10.7554/eLife.24241.001 PMID:28414271

Antibiotics as deep modulators of gut microbiota: between good and evil.

PubMed

Ianiro, Gianluca; Tilg, Herbert; Gasbarrini, Antonio

2016-11-01

The recent increase in our knowledge of human gut microbiota has changed our view on antibiotics. Antibiotics are, indeed, no longer considered only beneficial, but also potentially harmful drugs, as their abuse appears to play a role in the pathogenesis of several disorders associated with microbiota impairment (eg, Clostridium difficile infection or metabolic disorders). Both drug-related factors (such as antibiotic class, timing of exposure or route of administration) and host-related factors appear to influence the alterations of human gut microbiota produced by antibiotics. Nevertheless, antibiotics are nowadays considered a reliable therapy for some non-communicable disorders, including IBS or hepatic encephalopathy. Moreover, some antibiotics can also act positively on gut microbiota, providing a so-called 'eubiotic' effect, by increasing abundance of beneficial bacteria. Therefore, antibiotics appear to change, for better or worse, the nature of several disorders, including IBS, IBD, metabolic disorders or liver disease. This reviews aims to address the potential of antibiotics in the development of major non-communicable disorders associated with the alteration of gut microbiota and on newly discovered therapeutic avenues of antibiotics beyond the cure of infectious diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis.

PubMed

Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

2015-04-07

Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

Approach to the Hypophosphatemic Patient

PubMed Central

Imel, Erik A.

2012-01-01

Hypophosphatemia is commonly missed due to nonspecific signs and symptoms, but it causes considerable morbidity and in some cases contributes to mortality. Three primary mechanisms of hypophosphatemia exist: increased renal excretion, decreased intestinal absorption, and shifts from the extracellular to intracellular compartments. Renal hypophosphatemia can be further divided into fibroblast growth factor 23-mediated or non-fibroblast growth factor 23-mediated causes. Proper diagnosis requires a thorough medication history, family history, physical examination, and assessment of renal tubular phosphate handling to identify the cause. During the past decade, our understanding of phosphate metabolism has grown greatly through the study of rare disorders of phosphate homeostasis. Treatment of hypophosphatemia depends on the underlying disorder and requires close biochemical monitoring. This article illustrates an approach to the hypophosphatemic patient and discusses normal phosphate metabolism. PMID:22392950

Insulin resistance, metabolic stress, and atherosclerosis

PubMed Central

Pansuria, Meghana; Xi, Hang; Li, Le; Yang, Xiao-Feng; Wang, Hong

2012-01-01

Atherosclerosis, a pathological process that underlies the development of cardiovascular disease, is the primary cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). T2DM is characterized by hyperglycemia and insulin resistance (IR), in which target tissues fail to respond to insulin. Systemic IR is associated with impaired insulin signaling in the metabolic tissues and vasculature. Insulin receptor is highly expressed in the liver, muscle, pancreas, and adipose tissue. It is also expressed in vascular cells. It has been suggested that insulin signaling in vascular cells regulates cell proliferation and vascular function. In this review, we discuss the association between IR, metabolic stress, and atherosclerosis with focus on 1) tissue and cell distribution of insulin receptor and its differential signaling transduction and 2) potential mechanism of insulin signaling impairment and its role in the development of atherosclerosis and vascular function in metabolic disorders including hyperglycemia, hypertension, dyslipidemia, and hyperhomocysteinemia. We propose that insulin signaling impairment is the foremost biochemical mechanism underlying increased cardiovascular morbidity and mortality in atherosclerosis, T2DM, and metabolic syndrome. PMID:22202099

[Metabolic syndrome and bipolar disorder: Is sleep the missing link?

PubMed

Brochard, H; Boudebesse, C; Henry, C; Godin, O; Leboyer, M; Étain, B

2016-12-01

To examine the pathophysiologic mechanisms that may link circadian disorder and metabolic syndrome in bipolar disorder (BP). A systematic review of the literature was conducted from January 2013 to January 2015, using the Medline and Cochrane databases, using the keywords "metabolic syndrome", "obesity", "leptin" and "circadian disorders", "sleeping disorders" and cross-referencing them with "bipolar disorder". The following types of publications were candidates for review: (i) clinical trials; (ii) studies involving patients diagnosed with bipolar disorder; (iii) studies involving patients with sleeping disorder; or (iv) data about metabolic syndrome. Forty articles were selected. The prevalence of metabolic syndrome in BP was significantly higher compared to the general population (from 36 to 49% in the USA [Vancampfort, 2013]), and could be explained by several factors including reduced exercise and poor diet, genetic vulnerability, frequent depressive episodes, psychiatric comorbidity and psychotropic treatment. This high frequency of metabolic syndrome worsens the prognosis of these patients, increasing morbidity and mortality. Secondly, patients with BP experienced circadian and sleep disturbance, including modification in melatonin secretion. These perturbations are known to persist in periods of mood stabilization and are found in patients' relatives. Circadian disturbances are factors of relapse in bipolar patients, and they may also have a role in the metabolic comorbidities of these patients. Recent studies show that in populations of patients with bipolar disorder, a correlation between circadian disturbance and metabolic parameters are found. To identify the pathophysiological pathway connecting both could lead to a better comprehension of the disease and new therapeutics. In the overall population, mechanisms have been identified linking circadian and metabolic disorder involving hormones like leptin and ghrelin. These hormones are keys to regulation of energy balance in the organism, via their action on the hypothalamus, and are also regulated by sleep. We have hypothesized that these pathways could be implicated in the vulnerability of bipolar patients to metabolic syndrome. This hypothesis is supported by several studies showing dysregulation in leptin and ghrelin secretion in multiple psychiatric disorders, including bipolar disorder, as well as genetic variations of leptin and ghrelin genes in these diseases. We also assume that other mechanisms may be at stake to explain this link, such as melatonin dysregulation and inflammation. Circadian and sleeping disorder may have a role in the prevalence of metabolic syndrome in BP. Hormones like leptin and ghrelin could be the link between these perturbations. Prevention and treatment of circadian disorder in BP may greatly reduce the occurrence of MetS in these patients. Being aware of this statement and taking care of these troubles should be a big step forward for treatment of BP. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Noninvasive metabolic profiling for painless diagnosis of human diseases and disorders.

PubMed

Mal, Mainak

2016-06-01

Metabolic profiling provides a powerful diagnostic tool complementary to genomics and proteomics. The pain, discomfort and probable iatrogenic injury associated with invasive or minimally invasive diagnostic methods, render them unsuitable in terms of patient compliance and participation. Metabolic profiling of biomatrices like urine, breath, saliva, sweat and feces, which can be collected in a painless manner, could be used for noninvasive diagnosis. This review article covers the noninvasive metabolic profiling studies that have exhibited diagnostic potential for diseases and disorders. Their potential applications are evident in different forms of cancer, metabolic disorders, infectious diseases, neurodegenerative disorders, rheumatic diseases and pulmonary diseases. Large scale clinical validation of such diagnostic methods is necessary in future.

Noninvasive metabolic profiling for painless diagnosis of human diseases and disorders

PubMed Central

Mal, Mainak

2016-01-01

Metabolic profiling provides a powerful diagnostic tool complementary to genomics and proteomics. The pain, discomfort and probable iatrogenic injury associated with invasive or minimally invasive diagnostic methods, render them unsuitable in terms of patient compliance and participation. Metabolic profiling of biomatrices like urine, breath, saliva, sweat and feces, which can be collected in a painless manner, could be used for noninvasive diagnosis. This review article covers the noninvasive metabolic profiling studies that have exhibited diagnostic potential for diseases and disorders. Their potential applications are evident in different forms of cancer, metabolic disorders, infectious diseases, neurodegenerative disorders, rheumatic diseases and pulmonary diseases. Large scale clinical validation of such diagnostic methods is necessary in future. PMID:28031956

Opportunities for genetic improvement of metabolic diseases

USDA-ARS?s Scientific Manuscript database

Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors and status of gene...

Nature and Nurture in the Early-Life Origins of Metabolic Syndrome.

PubMed

Gonzalez-Bulnes, Antonio; Astiz, Susana; Ovilo, Cristina; Garcia-Contreras, Consolacion; Vazquez-Gomez, Marta

The combination of genetic background together with food excess and lack of exercise has become the cornerstone of metabolic disorders associated to lifestyle. The scenario is furthermore reinforced by their interaction with other environmental factors (stress, sleeping patterns, education, culture, rural versus urban locations, and xenobiotics, among others) inducing epigenetic changes in the exposed individuals. The immediate consequence is the development of further alterations like obesity and metabolic syndrome, and other adverse health conditions (type-2 diabetes, cardiovascular diseases, cancer, reproductive, immune and neurological disorders). Thus, having in mind the impact of the metabolic syndrome on the worldwide public health, the present review affords the relative roles and the interrelationships of nature (genetic predisposition to metabolic syndrome) and nurture (lifestyle and environmental effects causing epigenetic changes), on the establishment of the metabolic disorders in women; disorders that may evolve to metabolic syndrome prior or during pregnancy and may be transmitted to their descendants.

Eicosapentaenoic acid prevents high fat diet-induced metabolic disorders: Genomic and metabolomic analyses of underlying mechanism

USDA-ARS?s Scientific Manuscript database

Previously our lab demonstrated eicosapenaenoic acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity by decreasing insulin resistance, glucose intolerance and inflammation. In the current study, we used genomic and metabolomic approaches to further investigate the molecular basis for t...

Neurological Consequences of Obesity

PubMed Central

O’Brien, Phillipe D.; Hinder, Lucy M.; Callaghan, Brian C.; Feldman, Eva L.

2017-01-01

Obesity, primarily a consequence of poor dietary choices and an increased sedentary lifestyle, has become a global pandemic that brings with it enormous medical, social, and economic challenges. Not only does obesity increase the risk of cardiovascular disease and certain cancers, but it is also recognized as a key driver of other metabolic syndrome (MetS) components. These components include insulin resistance, hyperglycemia with prediabetes or type 2 diabetes, dyslipidemia, and hypertension, and are underlying contributors to systemic metabolic dysfunction. More recently, obesity and diet-induced metabolic dysfunction have been identified as risk factors for the development of a wide variety of neurological disorders in both the central and peripheral nervous systems. An abundance of literature has shown that obesity is associated with mild cognitive impairment and altered hippocampal structure and function, and there is a robust correlation between obesity and Alzheimer’s type dementia. Similarly, many reports show that both the autonomic and somatic components of the peripheral nervous system are impacted by obesity. The autonomic nervous system, under control of the hypothalamus, displays altered catabolic and anabolic processes in obese individuals attributed to sympathetic-parasympathetic imbalances. A close association also exists between obesity and polyneuropathy, a complication most commonly found in prediabetic and diabetic patients, and is likely secondary to a combination of obesity-induced dyslipidemia with hyperglycemia. This review will outline the pathophysiological development of obesity and dyslipidemia, discuss the adverse impact of these conditions on the nervous system, and provide evidence for lipotoxicity and metabolic inflammation as the drivers underlying the neurological consequences of obesity. In addition, this review will examine the benefits of lifestyle and surgical interventions in obesity-induced neurological disorders. PMID:28504110

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.

PubMed

Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer Mi; Doh, Kyung-Oh; Hui, Chi-Chung; Sung, Hoon-Ki

2017-11-01

Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage

PubMed Central

Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer MI; Doh, Kyung-Oh; Hui, Chi-chung; Sung, Hoon-Ki

2017-01-01

Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders. PMID:29039412

New innovations: therapeutic opportunities for intellectual disabilities.

PubMed

Picker, Jonathan D; Walsh, Christopher A

2013-09-01

Intellectual disability is common and is associated with significant morbidity. Until the latter half of the 20th century, there were no efficacious treatments. Following initial breakthroughs associated with newborn screening and metabolic corrections, little progress was made until recently. With improved understanding of genetic and cellular mechanisms, novel treatment options are beginning to appear for a number of specific conditions. Fragile X and tuberous sclerosis offer paradigms for the development of targeted therapeutics, but advances in understanding of other disorders such as Down syndrome and Rett syndrome, for example, are also resulting in promising treatment directions. In addition, better understanding of the underlying neurobiology is leading to novel developments in enzyme replacement for storage disorders and adjunctive therapies for metabolic disorders, as well as potentially more generalizable approaches that target dysfunctional cell regulation via RNA and chromatin. Physiologic therapies, including deep brain stimulation and transcranial magnetic stimulation, offer yet another direction to enhance cognitive functioning. Current options and evolving opportunities for the intellectually disabled are reviewed and exemplified. Copyright © 2013 American Neurological Association.

Urea cycle disorders: a life-threatening yet treatable cause of metabolic encephalopathy in adults.

PubMed

Blair, Nicholas F; Cremer, Philip D; Tchan, Michel C

2015-02-01

Urea cycle disorders are inborn errors of metabolism that, in rare cases, can present for the first time in adulthood. We report a perplexing presentation in a woman 4 days postpartum of bizarre and out-of-character behaviour interspersed with periods of complete normality. Without any focal neurological signs or abnormality on initial investigations, the diagnosis became clear with the finding of a significantly elevated plasma ammonia level, just as she began to deteriorate rapidly. She improved following intravenous dextrose and lipid emulsion, together with sodium benzoate, arginine and a protein-restricted diet. She remains well 12 months later with no permanent sequelae. Whilst this is a rare presentation of an uncommon disease, it is a treatable disorder and its early diagnosis can prevent a fatal outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Redox Properties of Tryptophan Metabolism and the Concept of Tryptophan Use in Pregnancy

PubMed Central

Xu, Kang; Liu, Hongnan; Bai, Miaomiao; Gao, Jing; Wu, Xin; Yin, Yulong

2017-01-01

During pregnancy, tryptophan (Trp) is required for several purposes, and Trp metabolism varies over time in the mother and fetus. Increased oxidative stress (OS) with high metabolic, energy and oxygen demands during normal pregnancy or in pregnancy-associated disorders has been reported. Taking the antioxidant properties of Trp and its metabolites into consideration, we made four hypotheses. First, the use of Trp and its metabolites is optional based on their antioxidant properties during pregnancy. Second, dynamic Trp metabolism is an accommodation mechanism in response to OS. Third, regulation of Trp metabolism could be used to control/attenuate OS according to variations in Trp metabolism during pregnancy. Fourth, OS-mediated injury could be alleviated by regulation of Trp metabolism in pregnancy-associated disorders. Future studies in normal/abnormal pregnancies and in associated disorders should include measurements of free Trp, total Trp, Trp metabolites, and activities of Trp-degrading enzymes in plasma. Abnormal pregnancies and some associated disorders may be associated with disordered Trp metabolism related to OS. Mounting evidence suggests that the investigation of the use of Trp and its metabolites in pregnancy will be meanful. PMID:28737706

Alterations of the cerebellum and basal ganglia in bipolar disorder mood states detected by quantitative T1ρ mapping.

PubMed

Johnson, Casey P; Christensen, Gary E; Fiedorowicz, Jess G; Mani, Merry; Shaffer, Joseph J; Magnotta, Vincent A; Wemmie, John A

2018-06-01

Quantitative mapping of T1 relaxation in the rotating frame (T1ρ) is a magnetic resonance imaging technique sensitive to pH and other cellular and microstructural factors, and is a potentially valuable tool for identifying brain alterations in bipolar disorder. Recently, this technique identified differences in the cerebellum and cerebral white matter of euthymic patients vs healthy controls that were consistent with reduced pH in these regions, suggesting an underlying metabolic abnormality. The current study built upon this prior work to investigate brain T1ρ differences across euthymic, depressed, and manic mood states of bipolar disorder. Forty participants with bipolar I disorder and 29 healthy control participants matched for age and gender were enrolled. Participants with bipolar disorder were imaged in one or more mood states, yielding 27, 12, and 13 imaging sessions in euthymic, depressed, and manic mood states, respectively. Three-dimensional, whole-brain anatomical images and T1ρ maps were acquired for all participants, enabling voxel-wise evaluation of T1ρ differences between bipolar mood state and healthy control groups. All three mood state groups had increased T1ρ relaxation times in the cerebellum compared to the healthy control group. Additionally, the depressed and manic groups had reduced T1ρ relaxation times in and around the basal ganglia compared to the control and euthymic groups. The study implicated the cerebellum and basal ganglia in the pathophysiology of bipolar disorder and its mood states, the roles of which are relatively unexplored. These findings motivate further investigation of the underlying cause of the abnormalities, and the potential role of altered metabolic activity in these regions. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of Citrus Flavonoids, Naringin and Naringenin, on Metabolic Syndrome and Their Mechanisms of Action12

PubMed Central

Alam, M. Ashraful; Subhan, Nusrat; Rahman, M. Mahbubur; Uddin, Shaikh J.; Reza, Hasan M.; Sarker, Satyajit D.

2014-01-01

Flavonoids are important natural compounds with diverse biologic activities. Citrus flavonoids constitute an important series of flavonoids. Naringin and its aglycone naringenin belong to this series of flavonoids and were found to display strong anti-inflammatory and antioxidant activities. Several lines of investigation suggest that naringin supplementation is beneficial for the treatment of obesity, diabetes, hypertension, and metabolic syndrome. A number of molecular mechanisms underlying its beneficial activities have been elucidated. However, their effect on obesity and metabolic disorder remains to be fully established. Moreover, the therapeutic uses of these flavonoids are significantly limited by the lack of adequate clinical evidence. This review aims to explore the biologic activities of these compounds, particularly on lipid metabolism in obesity, oxidative stress, and inflammation in context of metabolic syndrome. PMID:25022990

Emerging Drugs and Indications for Cardio-Metabolic Disorders in People with Severe Mental Illness.

PubMed

Kouidrat, Youssef; Amad, Ali; De Hert, Marc

2015-01-01

Patients with severe mental illnesses, such as schizophrenia and bipolar disorder, are at increased risk of developing metabolic disorders including obesity, diabetes, and dyslipidemia. All of these comorbidities increase the risk of cardiovascular disease and mortality. Different approaches, including diet and lifestyle modifications, behavioral therapy and switching antipsychotic agents, have been proposed to manage these metabolic abnormalities. However, these interventions may be insufficient, impractical or fail to counteract the metabolic dysregulation. Consequently, a variety of pharmacological agents such as antidiabetic drugs, have been studied in an attempt to reverse the weight gain and metabolic abnormalities evident in these patients. Despite a significant effect, many of these treatments are used off-label. This qualitative review focuses on pharmacological agents that could offer significant benefits in the management of cardio-metabolic disorders associated with serious mental illness.

Increased white matter metabolic rates in autism spectrum disorder and schizophrenia.

PubMed

Mitelman, Serge A; Buchsbaum, Monte S; Young, Derek S; Haznedar, M Mehmet; Hollander, Eric; Shihabuddin, Lina; Hazlett, Erin A; Bralet, Marie-Cecile

2017-11-22

Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used 18 fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.

Bifidobacteria attenuate the development of metabolic disorders, with inter- and intra-species differences.

PubMed

Zhu, Guangsu; Ma, Fangli; Wang, Gang; Wang, Yuanyuan; Zhao, Jianxin; Zhang, Hao; Chen, Wei

2018-06-20

Host gut microbiota dysbiosis occurs for multiple reasons and is often accompanied by chronic inflammation induced by a high-fat-high-sucrose (HFHS) diet and related metabolic disorders. Intervention with probiotics is a novel strategy for amelioration of metabolic syndrome, which is believed to regulate the gut microbiota composition to some extent. We investigated the relationship amongst bifidobacteria treatment, HFHS diet-induced metabolic disorders and the gut microbiota composition. Seven strains of bifidobacteria from four species were individually administered to rats fed a HFHS diet for 12 weeks. Various bifidobacteria strains showed various effects on the recovery of metabolic disorders and gut microbiota dysbiosis, and these effects seemed to be inter- or intra-species specific. Bifidobacterium longum, B. adolescentis and B. bifidum seemed to affect the blood glucose balance, whilst two strains of B. breve showed extremely different effects in this area. However, only one strain of B. longum and the B. adolescentis displayed significant regulation of blood lipid levels. The protective effects of bifidobacteria on the pancreas were strongly correlated with those on blood glucose. Furthermore, the influence of bifidobacteria on gut microbiota dysbiosis also showed a potential relationship with symptoms of metabolic disorders. Of these seven strains, B. adolescentis Z25 displayed an outstanding ability to alleviate metabolic syndrome, including glucose and lipid metabolism disorders, tissue damage and gut microbiota dysbiosis. This strain, coupled with other prebiotics and probiotics, could be used as a potential treatment approach for metabolic syndrome induced by a HFHS diet.

MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis

ClinicalTrials.gov

2018-01-19

Mucopolysaccharidosis Disorders; Hurler Syndrome; Hunter Syndrome; Maroteaux Lamy Syndrome; Sly Syndrome; Alpha-Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Glycoprotein Metabolic Disorders; Sphingolipidoses; Recessive Leukodystrophies; Globoid Cell Leukodystrophy; Metachromatic Leukodystrophy; Niemann-Pick B; Niemann-Pick C Subtype 2; Sphingomyelin Deficiency; Peroxisomal Disorders; Adrenoleukodystrophy With Cerebral Involvement; Zellweger Syndrome; Neonatal Adrenoleukodystrophy; Infantile Refsum Disease; Acyl-CoA Oxidase Deficiency; D-Bifunctional Enzyme Deficiency; Multifunctional Enzyme Deficiency; Alpha-methylacyl-CoA Racmase Deficiency; Mitochondrial Neurogastrointestingal Encephalopathy; Severe Osteopetrosis; Hereditary Leukoencephalopathy With Axonal Spheroids (HDLS; CSF1R Mutation); Inherited Metabolic Disorders

β-Thalassemia Patients Revealed a Significant Change of Untargeted Metabolites in Comparison to Healthy Individuals

PubMed Central

Musharraf, Syed Ghulam; Iqbal, Ayesha; Ansari, Saqib Hussain; Parveen, Sadia; Khan, Ishtiaq Ahmad; Siddiqui, Amna Jabbar

2017-01-01

β-Thalassemia is one of the most prevalent forms of congenital blood disorders characterized by reduced hemoglobin levels with severe complications, affecting all dimensions of life. The mechanisms underlying the phenotypic heterogeneity of β-thalassemia are still poorly understood. We aimed to work over metabolite biomarkers to improve mechanistic understanding of phenotypic heterogeneity and hence better management of disorder at different levels. Untargeted serum metabolites were analyzed after protein precipitation and SPE (solid phase extraction) from 100 β-thalassemia patients and 61 healthy controls using GC-MS. 40 metabolites were identified having a significance difference between these two groups at probability of 0.05 and fold change >1.5. Out of these 40 metabolites, 17 were up-regulated while 23 were down-regulated. PCA and PLS-DA model was also created that revealed a fine separation with a sensitivity of 70% and specificity of 100% on external validation of samples. Metabolic pathway analysis revealed alteration in multiple pathways including glycolysis, pyruvate, propanoate, glycerophospholipid, galactose, fatty acid, starch and sucrose metabolism along with fatty acid elongation in mitochondria, glycerolipid, glyoxylate and dicarboxylate metabolism pointing towards the shift of metabolism in β-thalassemia patients in comparison to healthy individuals. PMID:28198811

Perinatal Exposure to Perfluorooctane Sulfonate Affects Glucose Metabolism in Adult Offspring

PubMed Central

Wan, Hin T.; Zhao, Yin G.; Leung, Pik Y.; Wong, Chris K. C.

2014-01-01

Perfluoroalkyl acids (PFAAs) are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0) were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21). To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders. PMID:24498028

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

PubMed Central

Huang, Joanne H.; Berkovitch, Shaunna S.; Iaconelli, Jonathan; Watmuff, Bradley; Park, Hyoungjun; Chattopadhyay, Shrikanta; McPhie, Donna; Öngür, Dost; Cohen, Bruce M.; Clish, Clary B.; Karmacharya, Rakesh

2016-01-01

Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects showed distinct separation by principal components analysis methods. The most statistically significant findings were observed in the perturbation experiments. The metabolite with the lowest p value in both the low-glucose and dexamethasone experiments was α-aminoadipate, whose intracellular level was consistently lower in bipolar subjects. Our study implicates α-aminoadipate as a possible biomarker in bipolar disorder that manifests under cellular stress. This is an intriguing finding given the known role of α-aminoadipate in the modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid levels have been implicated in bipolar disorder. PMID:27606323

Acid-base and electrolyte disorders in patients with diabetes mellitus.

PubMed

Sotirakopoulos, Nikolaos; Kalogiannidou, Irini; Tersi, Maria; Armentzioiou, Karmen; Sivridis, Dimitrios; Mavromatidis, Konstantinos

2012-01-01

Diabetes mellitus is the most common metabolic disorder in the community. The diabetics may suffer from acid-base and electrolyte disorders due to complications of diabetes mellitus and the medication they receive. In this study, acid-base and electrolyte disorders were evaluated among outpatient diabetics in our hospital. The study consisted of patients with diabetes mellitus who visited the hospital as outpatients between the period January 1, 2004 to December 31, 2006. The patients' medical history, age and type of diabetes were noted, including whether they were taking diuretics and calcium channel blockers or not. Serum creatinine, proteins, sodium, potassium and chloride and blood gases were measured in all patients. Proteinuria was measured by 24-h urine collection. Two hundred and ten patients were divided in three groups based on the serum creatinine. Group A consisted of 114 patients that had serum creatinine < 1.2 mg/dL, group B consisted of 69 patients that had serum creatinine ranging from 1.3 to 3 mg/dL and group C consisted of 27 patients with serum creatinine > 3.1 mg/dL. Of the 210 patients, 176 had an acid-base disorder. The most common disorder noted in group A was metabolic alkalosis. In groups B and C, the common disorders were metabolic acidosis and alkalosis, and metabolic acidosis, respectively. The most common electrolyte disorders were hypernatremia (especially in groups A and B), hyponatremia (group C) and hyperkalemia (especially in groups B and C). It is concluded that: (a) in diabetic outpatients, acid-base and electrolyte disorders occurred often even if the renal function is normal, (b) the most common disorders are metabolic alkalosis and metabolic acidosis (the frequency increases with the deterioration of the renal function) and (c) the common electrolyte disorders are hypernatremia and hypokalemia.

Phenylketonuria as a model for protein misfolding diseases and for the development of next generation orphan drugs for patients with inborn errors of metabolism.

PubMed

Muntau, Ania C; Gersting, Søren W

2010-12-01

The lecture dedicated to Professor Horst Bickel describes the advances, successes, and opportunities concerning the understanding of the biochemical and molecular basis of phenylketonuria and the innovative treatment strategies introduced for these patients during the last 60 years. These concepts were transferred to other inborn errors of metabolism and led to significant reduction in morbidity and to an improvement in quality of life. Important milestones were the successful development of a low-phenylalanine diet for phenylketonuria patients, the recognition of tetrahydrobiopterin as an option to treat these individuals pharmacologically, and finally market approval of this drug. The work related to the discovery of a pharmacological treatment led metabolic researchers and pediatricians to new insights into the molecular processes linked to mutations in the phenylalanine hydroxylase gene at the cellular and structural level. Again, phenylketonuria became a prototype disorder for a previously underestimated but now rapidly expanding group of diseases: protein misfolding disorders with loss of function. Due to potential general biological mechanisms underlying these disorders, the door may soon open to a systematic development of a new class of pharmaceutical products. These pharmacological chaperones are likely to correct misfolding of proteins involved in numerous genetic and nongenetic diseases.

Metabolic syndrome in Tunisian bipolar I patients.

PubMed

Ezzaher, A; Haj, Mouhamed D; Mechri, A; Neffati, F; Douki, W; Gaha, L; Najjar, M F

2011-09-01

The metabolic syndrome is a growing global public health problem which is frequently associated with psychiatric illness. To evaluate the prevalence of metabolic syndrome and to study its profile in Tunisian bipolar I patients. Our study included 130 patients with bipolar I disorder diagnosed according to the DSM-IV and assessed for metabolic syndrome according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III modified criteria. The mean age was 37.9 ± 12.1 years, 45 were women (mean age 37.5 ± 13.4 years) and 85 were men (mean age 38.1 ± 11.4 years). The prevalence of metabolic syndrome was 26.1%.The highest prevalence of this syndrome was obtained by association between obesity, low c-HDL and hypertriglyceridemia (44.1%). In the total sample, 59.2% met the criteria for low c-HDL, 53.1% for hypertriglyceridemia, 33.8% for obesity, 16.1% for high fasting glucose and 5.4% for hypertension. Gender, age, illness episode and treatment were not significantly associated with metabolic syndrome, while patients under lithium had higher prevalence of metabolic syndrome than those under valproic acid, carbamazepine or antipsychotics. Patients with metabolic syndrome had significant higher levels of HOMA-IR and uric acid than metabolic syndrome free patients (p< 0.001). Bipolar patients have high prevalence of metabolic syndrome which is associated with insulin resistance and an increase of uric acid values that raise the risk of cardiovascular disease.

[Rhabdomyolysis - may it be a metabolic myopathy? Case report and diagnostic algorithm].

PubMed

Sebők, Ágnes; Pál, Endre; Molnár, Gergő Attila; Wittmann, István; Berenténé Bene, Judit; Melegh, Béla; Komoly, Sámuel; Hidvégi, Tibor; Balogh, Lídia; Szabó, Attila; Zsidegh, Petra

2017-11-01

We report the case of a 46-year-old female patient with recurrent rhabdomyolysis. In the background of her metabolic myopathy an inherited metabolic disorder of the fatty acid oxidation, very long-chain acyl-coenzyme A-dehydrogenase deficiency was diagnosed. The diagnosis was based on abnormal acyl-carnitine- and urine organic-acid profile in addition to low residual enzyme activity, and was confirmed by genetic testing. After introduction of dietotherapy metabolic crisis necessitating hospital admission has not occurred neither have fixed myopathic changes developed. We present here the differential diagnosis of rhabdomyolysis and exertional muscle complaints, with the metabolic myopathies in focus. The main features of fatty acid oxidation disorders are highlighted, acute and chronic managements of very long-chain acyl-coenzyme A-dehydrogenase deficiency are discussed. Metabolic myopathies respond well to treatment, so good quality of life can be achieved. However, especially in fatty acid oxidation disorders, a metabolic crisis may develop quickly and can be fatal, albeit rarely. Some of these disorders can be identified by newborn screening, but occasionally the symptoms may manifest only in adulthood. With the presentation of this case we would like to point out that in the differential diagnosis of recurrent rhabdomyolysis inherited metabolic disorders should be considered regardless of the patient's age. Orv Hetil. 2017; 158(46): 1873-1882.

Breast milk feeding in infants with inherited metabolic disorders other than phenylketonuria - a 10-year single-center experience.

PubMed

Pichler, Karin; Michel, Miriam; Zlamy, Manuela; Scholl-Buergi, Sabine; Ralser, Elisabeth; Jörg-Streller, Monika; Karall, Daniela

2017-04-01

Published data on breast milk feeding in infants suffering from inherited metabolic disorders (IMDs) other than phenylketonuria (PKU) are limited and described outcome is variable. We aimed to evaluate retrospectively whether breastfeeding and/or breast milk feeding are feasible in infants with IMDs including organic acidemias, fatty acid oxidation disorders, urea cycle disorders, aminoacidopathies or disorders of galactose metabolism. Data on breastfeeding and breast milk feeding as well as monitoring and neurological outcome were collected retrospectively from our database of patients with the mentioned IMD, who were followed in our metabolic center within the last 10 years. Twenty patients were included in the study, who were either breast fed on demand or received expressed breast milk. All the infants were evaluated clinically and biochemically at 2-4-week intervals, with weight gain as the leading parameter to determine metabolic control. Good metabolic control and adequate neurological development were achieved in all patients but one, who experienced the only metabolic crisis observed within the study period. Breast milk feeding with close clinical and biochemical monitoring is feasible in most IMD and should be considered as it offers nutritional and immunological benefits.

Disorders of Bilirubin Metabolism

PubMed Central

1966-01-01

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California Medical Center, San Francisco. They are prepared from transcriptions by Drs. Martin J. Cline and Hibbard E. Williams, Assistant Professors of Medicine, under the direction of Dr. Lloyd H. Smith, Professor of Medicine and Chairman of the Department of Medicine. PMID:5909869

What choline metabolism can tell us about the underlying mechanisms of fetal alcohol spectrum disorders.

PubMed

Zeisel, Steven H

2011-10-01

The consequences of fetal exposure to alcohol are very diverse and the likely molecular mechanisms involved must be able to explain how so many developmental processes could go awry. If pregnant rat dams are fed alcohol, their pups develop abnormalities characteristic of fetal alcohol spectrum disorders (FASD), but if these rat dams were also treated with choline, the effects from ethanol were attenuated in their pups. Choline is an essential nutrient in humans, and is an important methyl group donor. Alcohol exposure disturbs the metabolism of choline and other methyl donors. Availability of choline during gestation directly influences epigenetic marks on DNA and histones, and alters gene expression needed for normal neural and endothelial progenitor cell proliferation. Maternal diets low in choline alter development of the mouse hippocampus, and decrement memory for life. Women eating low-choline diets have an increased risk of having an infant with a neural tube or orofacial cleft birth defect. Thus, the varied effects of choline could affect the expression of FASD, and studies on choline might shed some light on the underlying molecular mechanisms responsible for FASD.

Mechanisms of Divalent Metal Toxicity in Affective Disorders

PubMed Central

Menon, Archita Venugopal; Chang, JuOae; Kim, Jonghan

2016-01-01

Metals are required for proper brain development and play an important role in a number of neurobiological functions. The Divalent Metal Transporter 1 (DMT1) is a major metal transporter involved in the absorption and metabolism of several essential metals like iron and manganese. However, non-essential divalent metals are also transported through this transporter. Therefore, altered expression of DMT1 can modify the absorption of toxic metals and metal-induced toxicity. An accumulating body of evidence has suggested that increased metal stores in the brain are associated with elevated oxidative stress mediated by the ability of metals to catalyze redox reactions, resulting in abnormal neurobehavioral function and the progression of neurodegenerative diseases. Metal overload has also been implicated in impaired emotional behavior, although the underlying mechanisms are not well understood with limited information. The current review focuses on psychiatric dysfunction associated with imbalanced metabolism of metals that are transported by DMT1. The investigations with respect to the toxic effects of metal overload on behavior and their underlying mechanisms of toxicity could provide several new therapeutic targets to treat metal-associated affective disorders. PMID:26551072

Metabolic syndrome in patients with depressive disorder--features of comorbidity.

PubMed

Kozumplik, Oliver; Uzun, Suzana

2011-03-01

Depression is associated with increased physical morbidity and overall mortality. The results of a previous investigation on the relationship of the metabolic syndrome and its single components with coronary heart disease, cardiovascular disease (CVD), and all-cause mortality suggested that the metabolic syndrome is a marker of CVD risk, but not above and beyond the risk associated with its individual components. The aim of this article is to review literature regarding prevalence of metabolic syndrome in patients with depressive disorder, and association between metabolic syndrome and depression. Literature research included structured searches of Medline and other publications on the subject of metabolic syndrome, particularly prevalence of metabolic syndrome in patients with depressive disorder, and association between metabolic syndrome and depression. Prevalence of the metabolic syndrome in patients with depression is high and varies among the analysed studies. Some investigations showed association between metabolic syndrome and depression. Further investigations are necessary in order to clarify the association between metabolic syndrome and depression.

Acquired pendular nystagmus

PubMed Central

Kang, Sarah; Shaikh, Aasef G.

2017-01-01

Acquired pendular nystagmus is comprised of quasi-sinusoidal oscillations of the eyes significantly affecting gaze holding and clarity of vision. The most common causes of acquired pendular nystagmus include demyelinating disorders such as multiple sclerosis and the syndrome of ocular palatal tremor. However, several other deficits, such as pharmacological intoxication, metabolic and genetic disorders, and granulomatous disorders can lead to syndromes mimicking acquired pendular nystagmus. Study of the kinematic features of acquired pendular nystagmus has suggested a putative pathophysiology of an otherwise mysterious neurological disorder. Here we review clinical features of neurological deficits that co-occur with acquired pendular nystagmus. Subsequent discussion of the pathophysiology of individual forms of pendular nystagmus speculates on mechanisms of the underlying disease while providing insights into pharmacotherapy of nystagmus. PMID:28320194

(1)H NMR-based metabonomics revealed protective effect of Naodesheng bioactive extract on ischemic stroke rats.

PubMed

Luo, Lan; Zhen, Lifeng; Xu, Yatao; Yang, Yongxia; Feng, Suxiang; Wang, Shumei; Liang, Shengwang

2016-06-20

Stroke is a leading cause of death and disability in the world. However, current therapies are limited. Naodesheng, a widely used traditional Chinese medicine prescription, has shown a good clinical curative effect on ischemic stroke. Also, Naodesheng has been suggested to have neuroprotective effect on focal cerebral ischemia rats, but the underlying molecular mechanism remains unclear. The present study was designed to evaluate the effect of Naodesheng bioactive extract on the metabolic changes in brain tissue, plasma and urine induced by cerebral ischemia perfusion injury, and explore the possible metabolic mechanisms by using a (1)H NMR-based metabonomics approach. A middle cerebral artery occlusion rat model was established and confirmed by the experiments of neurobehavioral abnormality evaluation, brain tissue TTC staining and pathological examination. The metabolic changes in brain tissue, plasma and urine were then assessed by a (1)H NMR technique combined with multivariate statistical analysis method. These NMR data showed that cerebral ischemia reperfusion induced great metabolic disorders in brain tissue, plasma and urine metabolisms. However, Naodesheng bioactive extract could reverse most of the imbalanced metabolites. Meanwhile, it was found that both the medium and high dosages of Naodesheng bioactive extract were more effective on the metabolic changes than the low dosage, consistent with histopathological assessments. These results revealed that Naodesheng had protective effect on ischemic stroke rats and the underlying mechanisms involved multiple metabolic pathways, including energy metabolism, amino acid metabolism, oxidative stress and inflammatory injury. The present study could provide evidence that metabonomics revealed its capacity to evaluate the holistic efficacy of traditional Chinese medicine and explore the underlying mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2015-01-01

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

Mangiferin Modulation of Metabolism and Metabolic Syndrome

PubMed Central

Fomenko, Ekaterina Vladimirovna; Chi, Yuling

2016-01-01

The recent emergence of a worldwide epidemic of metabolic disorders, such as obesity and diabetes, demands effective strategy to develop nutraceuticals or pharmaceuticals to halt this trend. Natural products have long been and continue to be an attractive source of nutritional and pharmacological therapeutics. One such natural product is mangiferin (MGF), the predominant constituent of extracts of the mango plant Mangifera indica L. Reports on biological and pharmacological effects of MGF increased exponentially in recent years. MGF has documented antioxidant and anti-inflammatory effects. Recent studies indicate that it modulates multiple biological processes involved in metabolism of carbohydrates and lipids. MGF has been shown to improve metabolic abnormalities and disorders in animal models and humans. This review focuses on the recently reported biological and pharmacological effects of MGF on metabolism and metabolic disorders. PMID:27534809

[Characteristics of sodium metabolism in rats with experimental hypertension caused by chronic alimentary imbalance].

PubMed

Strekalova, V V; Khachirov, D G; Dedenkov, A N; Suvorov, Iu I

1991-01-01

Beginning from 1.5 month of life Wistar rats were kept under conditions of chronic 1 and 2% salt loading combined with a low-protein diet (6-8% of protein VS, as compared with 23-24% in the normal diet). At the age of 14-16 months when a stable hypertension developed due to the above alimentary imbalance, their sodium metabolism was studied using whole-body radiometry with 22Na. A three-chamber model of 22Na metabolism was developed for the analysis of 22Na excretion from the body. This helped in establishing the heterogeneity of sodium metabolism in experimental animals. Besides that, it has been shown that not only sodium retention in the body, but also its redistribution between intra- and extravascular sections play an important role in the development of hypertension. Protein deficiency in the diet aggravates sodium metabolism disorders in experimental animals.

Complications of Cushing's syndrome: state of the art.

PubMed

Pivonello, Rosario; Isidori, Andrea M; De Martino, Maria Cristina; Newell-Price, John; Biller, Beverly M K; Colao, Annamaria

2016-07-01

Cushing's syndrome is a serious endocrine disease caused by chronic, autonomous, and excessive secretion of cortisol. The syndrome is associated with increased mortality and impaired quality of life because of the occurrence of comorbidities. These clinical complications include metabolic syndrome, consisting of systemic arterial hypertension, visceral obesity, impairment of glucose metabolism, and dyslipidaemia; musculoskeletal disorders, such as myopathy, osteoporosis, and skeletal fractures; neuropsychiatric disorders, such as impairment of cognitive function, depression, or mania; impairment of reproductive and sexual function; and dermatological manifestations, mainly represented by acne, hirsutism, and alopecia. Hypertension in patients with Cushing's syndrome has a multifactorial pathogenesis and contributes to the increased risk for myocardial infarction, cardiac failure, or stroke, which are the most common causes of death; risks of these outcomes are exacerbated by a prothrombotic diathesis and hypokalaemia. Neuropsychiatric disorders can be responsible for suicide. Immune disorders are common; immunosuppression during active disease causes susceptibility to infections, possibly complicated by sepsis, an important cause of death, whereas immune rebound after disease remission can exacerbate underlying autoimmune diseases. Prompt treatment of cortisol excess and specific treatments of comorbidities are crucial to prevent serious clinical complications and reduce the mortality associated with Cushing's syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Metabolic syndrome - a new look at a known problem].

PubMed

Płaczkowska, Sylwia; Pawlik-Sobecka, Lilla; Kokot, Izabela; Piwowar, Agnieszka

Civilization changes over the past decades have been associated with an increase in the incidence of various metabolic disorders, especially in the carbohydrate-lipid metabolism, which are not always associated with obesity. Metabolic syndrome, despite changing criteria of recognition, is a clinically established risk factor for civilization diseases development. On the other side, the incidence of complex metabolic disorders in non-obese people is increasing, which is referred to in the literature as metabolic obesity with normal body mass. Both, excess visceral fatty tissue and insulin resistance are common components in the diagnosis of these syndromes and their occurrence is associated with an increased risk of developing type 2 diabetes and cardiovascular disease. Some researchers also point out the possibility of occurrence of so-called metabolically healthy obesity. Identify people with such a constellation of disorders is still difficult in clinical practice because of different and changing diagnostic criteria. Data from the literature about epidemiology of these disorders are inconclusive and do not allow for a reliable assessment of such disorders prevalence in population. The increasing rate of the metabolic syndrome and metabolic obesity with normal body weight occurrence in the general population pays attention to the importance of this problem, especially in primary health care. Preventive programs are primarily aimed at older people with high risk of cardiovascular diseases development and focused on detecting metabolic syndrome traits. Nevertheless, very often, young, potentially healthy individuals, are not subject to screening programs, even though incidence of metabolic obesity with normal body weight in this population is very high nowadays.

Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease-different clinical entities and comparable perinatal renal abnormalities.

PubMed

Hackl, Agnes; Mehler, Katrin; Gottschalk, Ingo; Vierzig, Anne; Eydam, Marcus; Hauke, Jan; Beck, Bodo B; Liebau, Max C; Ensenauer, Regina; Weber, Lutz T; Habbig, Sandra

2017-05-01

Differential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases. We report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case. Review of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD. Neonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early metabolic management.

Gut Microbiota and Metabolic Disorders

PubMed Central

Hur, Kyu Yeon

2015-01-01

Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders. PMID:26124989

Infant with cardiomyopathy: When to suspect inborn errors of metabolism?

PubMed Central

Byers, Stephanie L; Ficicioglu, Can

2014-01-01

Inborn errors of metabolism are identified in 5%-26% of infants and children with cardiomyopathy. Although fatty acid oxidation disorders, lysosomal and glycogen storage disorders and organic acidurias are well-known to be associated with cardiomyopathies, emerging reports suggest that mitochondrial dysfunction and congenital disorders of glycosylation may also account for a proportion of cardiomyopathies. This review article clarifies when primary care physicians and cardiologists should suspect inborn errors of metabolism in a patient with cardiomyopathy, and refer the patient to a metabolic specialist for a further metabolic work up, with specific discussions of “red flags” which should prompt additional evaluation. PMID:25429327

Dual Mode Action of Mangiferin in Mouse Liver under High Fat Diet

PubMed Central

Lim, Jihyeon; Liu, Zhongbo; Apontes, Pasha; Feng, Daorong; Pessin, Jeffrey E.; Sauve, Anthony A.; Angeletti, Ruth H.; Chi, Yuling

2014-01-01

Chronic over-nutrition is a major contributor to the spread of obesity and its related metabolic disorders. Development of therapeutics has been slow compared to the speedy increase in occurrence of these metabolic disorders. We have identified a natural compound, mangiferin (MGF) (a predominant component of the plants of Anemarrhena asphodeloides and Mangifera indica), that can protect against high fat diet (HFD) induced obesity, hyperglycemia, insulin resistance and hyperlipidemia in mice. However, the molecular mechanisms whereby MGF exerts these beneficial effects are unknown. To understand MGF mechanisms of action, we performed unbiased quantitative proteomic analysis of protein profiles in liver of mice fed with HFD utilizing 15N metabolically labeled liver proteins as internal standards. We found that out of 865 quantified proteins 87 of them were significantly differentially regulated by MGF. Among those 87 proteins, 50% of them are involved in two major processes, energy metabolism and biosynthesis of metabolites. Further classification indicated that MGF increased proteins important for mitochondrial biogenesis and oxidative activity including oxoglutarate dehydrogenase E1 (Dhtkd1) and cytochrome c oxidase subunit 6B1 (Cox6b1). Conversely, MGF reduced proteins critical for lipogenesis such as fatty acid stearoyl-CoA desaturase 1 (Scd1) and acetyl-CoA carboxylase 1 (Acac1). These mass spectrometry data were confirmed and validated by western blot assays. Together, data indicate that MGF upregulates proteins pivotal for mitochondrial bioenergetics and downregulates proteins controlling de novo lipogenesis. This novel mode of dual pharmacodynamic actions enables MGF to enhance energy expenditure and inhibit lipogenesis, and thereby correct HFD induced liver steatosis and prevent adiposity. This provides a molecular basis supporting development of MGF or its metabolites into therapeutics to treat metabolic disorders. PMID:24598864

Taxonomy of rare genetic metabolic bone disorders.

PubMed

Masi, L; Agnusdei, D; Bilezikian, J; Chappard, D; Chapurlat, R; Cianferotti, L; Devolgelaer, J-P; El Maghraoui, A; Ferrari, S; Javaid, M K; Kaufman, J-M; Liberman, U A; Lyritis, G; Miller, P; Napoli, N; Roldan, E; Papapoulos, S; Watts, N B; Brandi, M L

2015-10-01

This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

Gut Microbiome and Obesity: A Plausible Explanation for Obesity.

PubMed

Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A

2015-06-01

Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host's adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity.

Gut Microbiome and Obesity: A Plausible Explanation for Obesity

PubMed Central

Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A.

2015-01-01

Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host’s adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity. PMID:26029487

Cerebral glucose metabolic differences in patients with panic disorder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nordahl, T.E.; Semple, W.E.; Gross, M.

Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer (F-18)-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobulemore » and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task.« less

Metabolic consequences of sleep and circadian disorders

PubMed Central

Depner, Christopher M.; Stothard, Ellen R.; Wright, Kenneth P.

2014-01-01

Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed. PMID:24816752

Metabolic consequences of sleep and circadian disorders.

PubMed

Depner, Christopher M; Stothard, Ellen R; Wright, Kenneth P

2014-07-01

Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome, and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance, and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed.

Pathophysiological implications of neurovascular P450 in brain disorders

PubMed Central

Ghosh, Chaitali; Hossain, Mohammed; Solanki, Jesal; Dadas, Aaron; Marchi, Nicola; Janigro, Damir

2016-01-01

Over the past decades, the significance of cytochrome P450 (CYP) enzymes has expanded beyond their role as peripheral drug metabolizers in the liver and gut. CYP enzymes are also functionally active at the neurovascular interface. CYP expression is modulated by disease states, impacting cellular functions, detoxification, and reactivity to toxic stimuli and brain drug biotransformation. Unveiling the physiological and molecular complexity of brain P450 enzymes will improve our understanding of the mechanisms underlying brain drug availability, pharmacological efficacy, and neurotoxic adverse effects from pharmacotherapy targeting brain disorders. PMID:27312874

Emerging Role of Corticosteroid-Binding Globulin in Glucocorticoid-Driven Metabolic Disorders.

PubMed

Moisan, Marie-Pierre; Castanon, Nathalie

2016-01-01

Glucocorticoid hormones (GCs) are critical for survival since they ensure the energy supply necessary to the body in an ever challenging environment. GCs are known to act on appetite, glucose metabolism, fatty acid metabolism, and storage. However, to be beneficial to the body, GC levels should be maintained in an optimal window of concentrations. Not surprisingly, conditions of GC excess or deficiency, e.g., Cushing's syndrome or Addison's disease, are associated with severe alterations of energy metabolism. Corticosteroid-binding globulin (CBG), through its high specific affinity for GCs, plays a critical role in regulating plasma GC levels and their access to target cells. Genetic studies in various species including humans have revealed that CBG is the major factor influencing interindividual genetic variability of plasma GC levels, both in basal and stress conditions. Some, but not all, of these genetic studies have also provided data linking CBG levels to body composition and insulin levels. The examination of CBG-deficient mice submitted to hyperlipidic diets unveiled specific roles for CBG in lipid storage and metabolism. An influence of CBG on appetite has not been reported but remains to be more finely analyzed. Finally, only male mice have been examined under high-fat diet, while obesity is affecting women even more than men. Overall, a role of CBG in GC-driven metabolic disorders is emerging in recent studies. Although subtle, the influence of CBG in these diseases could open the way to new therapeutic interventions since CBG is easily accessible in the blood.

Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders.

PubMed

Pistorio, Elisabetta; Luca, Maria; Luca, Antonina; Messina, Vincenzo; Calandra, Carmela

2011-10-28

To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker. 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated. Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

Drug-induced cerebral glucose metabolism resembling Alzheimer's Disease: a case study.

PubMed

Riepe, Matthias W; Walther, Britta; Vonend, Catharina; Beer, Ambros J

2015-07-11

With aging of society the absolute number and the proportion of patients with cognitive deficits increase. Multiple disorders and diseases can foster cognitive impairment, e.g., Alzheimer's disease (AD), depressive disorder, or polypharmacy. A 74 year old man presented to the Old Age Psychiatry Service with cognitive deficits while being treated for recurrent depressive episodes and essential tremor with Venlafaxine, Lithium, and Primidone. Neuropsychological testing revealed a medio-temporal pattern of deficits with pronounced impairment of episodic memory, particularly delayed recall. Likewise, cognitive flexibility, semantic fluency, and attention were impaired. Positron emission tomography (PET) with fluorodeoxyglucose was performed and revealed a pattern of glucose utilization deficit resembling AD. On cessation of treatment with Lithium and Primidone, cognitive performance improved, particularly episodic memory performance and cognitive flexibility. Likewise, glucose metabolism normalized. Despite normalization of both, clinical symptoms and glucose utilization, the patient remained worried about possible underlying Alzheimer's disease pathology. To rule this out, an amyloid-PET was performed. No cortical amyloid was observed. Pharmacological treatment of older subjects may mimic glucose metabolism and clinical symptoms of Alzheimer's disease. In the present case both, imaging and clinical findings, reversed to normal on change of treatment. Amyloid PET is a helpful tool to additionally rule out underlying Alzheimer's disease in situations of clinical doubt even if clinical or other imaging findings are suggestive of Alzheimer's disease.

Biochemical abnormalities in neonatal seizures.

PubMed

Sood, Arvind; Grover, Neelam; Sharma, Roshan

2003-03-01

The presence of seizure does not constitute a diagnoses but it is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. Biochemical disturbances occur frequently in the neonatal seizures either as an underlying cause or as an associated abnormality. In their presence, it is difficult to control seizure and there is a risk of further brain damage. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long term outcome. The present study was conducted in the department of pediatrics in IGMC Shimla on 59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases. Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal seizures, most common being hypocalcaemia followed by hypoglycemia, other metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates. Associated metabolic abnormalities were observed more often with Hypoxic-ischemic-encephalopathy (11 out of 19) cases and hypoglycemia was most common in this group. No infant had hyponateremia, hyperkelemia or low zinc level.

The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged.

PubMed

Craft, Suzanne

2009-03-01

In recent years a rapidly increasing number of studies has focused on the relationship between dementia and metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. Etiological heterogeneity and comorbidity pose challenges for determining relationships among metabolic disorders. The independent and interactive effects of brain vascular injury and classic pathological agents such as beta-amyloid have also proved difficult to distinguish in human patients, blurring the lines between Alzheimer disease and vascular dementia. This review highlights recent work aimed at identifying convergent mechanisms such as insulin resistance that may underlie comorbid metabolic disorders and thereby increase dementia risk. Identification of such convergent factors will not only provide important insight into the causes and interdependencies of late-life dementias but will also inspire novel strategies for treating and preventing these disorders.

The Role of Metabolic Disorders in Alzheimer's Disease and Vascular Dementia: Two Roads Converged?

PubMed Central

Craft, Suzanne

2009-01-01

In recent years, there has been a rapidly increasing number of studies focused on the relationship between dementia and metabolic disorders such as diabetes, obesity, hypertension and dyslipidemia. Etiological heterogeneity and co-morbidity pose challenges for determining relationships among metabolic disorders. The independent and interactive effects of brain vascular injury and classic pathological agents such as Aβ have also proved difficult to untangle in human patients, blurring the lines between Alzheimer's disease and vascular dementia. This review highlights recent work aimed at identifying convergent mechanisms such as insulin resistance that may underlie co-morbid metabolic disorders and thereby increase dementia risk. Identification of such convergent factors will not only provide important insights into the causes and interdependencies of late-life dementias, but will also inspire novel strategies for treating and preventing these disorders. PMID:19273747

Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development

PubMed Central

Mueller, Kristina M.; Themanns, Madeleine; Friedbichler, Katrin; Kornfeld, Jan-Wilhelm; Esterbauer, Harald; Tuckermann, Jan P.; Moriggl, Richard

2012-01-01

Growth hormone (GH) and glucocorticoids (GCs) are involved in the control of processes that are essential for the maintenance of vital body functions including energy supply and growth control. GH and GCs have been well characterized to regulate systemic energy homeostasis, particular during certain conditions of physical stress. However, dysfunctional signaling in both pathways is linked to various metabolic disorders associated with aberrant carbohydrate and lipid metabolism. In liver, GH-dependent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 controls a variety of physiologic functions within hepatocytes. Similarly, GCs, through activation of the glucocorticoid receptor (GR), influence many important liver functions such as gluconeogenesis. Studies in hepatic Stat5 or GR knockout mice have revealed that they similarly control liver function on their target gene level and indeed, the GR functions often as a cofactor of STAT5 for GH-induced genes. Gene sets, which require physical STAT5–GR interaction, include those controlling body growth and maturation. More recently, it has become evident that impairment of GH-STAT5 signaling in different experimental models correlates with metabolic liver disease, ranging from hepatic steatosis to hepatocellular carcinoma (HCC). While GH-activated STAT5 has a protective role in chronic liver disease, experimental disruption of GC-GR signaling rather seems to ameliorate metabolic disorders under metabolic challenge. In this review, we focus on the current knowledge about hepatic GH-STAT5 and GC-GR signaling in body growth, metabolism, and protection from fatty liver disease and HCC development. PMID:22564914

Inherited metabolic disorders in Thailand.

PubMed

Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

2002-08-01

The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

The impact of race on metabolic disease risk factors in women with and without posttraumatic stress disorder.

PubMed

Dedert, Eric A; Harper, Leia A; Calhoun, Patrick S; Dennis, Michelle F; Beckham, Jean C

2013-03-01

The literature on PTSD and metabolic disease risk factors has been limited by lacking investigation of the potential influence of commonly comorbid disorders and the role of race. In this study data were provided by a sample of 134 women (63 PTSD and 71 without PTSD). Separate sets of models examining associations of psychiatric disorder classifications with metabolic disease risk factors were used. Each model included race (African American or Caucasian), psychiatric disorder, and their interaction. There was an interaction of race and PTSD on body mass index, abdominal obesity, and triglycerides. While PTSD was not generally associated with deleterious health effects in African American participants, PTSD was related to worse metabolic disease risk factors in Caucasians. MDD was associated with metabolic disease risk factors, but there were no interactions with race. Results support the importance of race in the relationship between PTSD and metabolic disease risk factors. Future research would benefit from analysis of cultural factors to explain how race might influence metabolic disease risk factors in PTSD.

Newborn screening tests

MedlinePlus

... adrenal hyperplasia Congenital hypothyroidism Cystic fibrosis Fatty acid metabolism disorders Galactosemia Glucose-6-phosphate dehydrogenase deficiency (G6PD) Human immunodeficiency disease (HIV) Organic acid metabolism disorders Phenylketonuria ( ...

Effect of low gravity on calcium metabolism and bone formation (L-7)

NASA Technical Reports Server (NTRS)

Suda, Tatsuo

1993-01-01

Recently, attention has been focused on the disorders of bone and calcium metabolism during space flight. The skeletal system has evolved on the Earth under 1-g. Space flights under low gravity appear to cause substantial changes in bone and calcium homeostasis of the animals adapted to 1-g. A space experiment for the First Materials Processing Test (FMPT) was proposed to examine the effects of low gravity on calcium metabolism and bone formation using chick embryos loaded in a space shuttle. This space experiment was proposed based on the following two experimental findings. First, it has been reported that bone density decreases significantly during prolonged space flight. The data obtained from the US Skylab and the U.S.S.R. Salyut-6 cosmonauts have also documented that the degree of bone loss is related to the duration of space flight. Second, the US-Soviet joints space experiment demonstrated that the decrease in bone density under low gravity appears to be due to the decrease in bone formation rather than the increase in bone resorption. The purpose of our space experiment is, therefore, to investigate further the mechanisms of bone growth under low gravity using fertilized chick embryos.

[Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Non- invasive assessment of bone turn over markers could define the cause of metabolic bone diseases].

PubMed

Suzuki, Atsushi

2011-09-01

Recent advances of the measurement of bone turn over markers contribute to non-invasive assessment of bone-metabolic disorders. We can detect the cause of the metabolic disorders with bone turn over markers and hormonal profiles more easily than before. Today, we can diagnose and treat metabolic bone diseases without invasive procedure such as bone biopsy.

Treatment strategies for acute metabolic disorders in neonates

PubMed Central

2011-01-01

Acute metabolic emergencies in neonates represent a challenge to the medical and nursing staff. If not treated optimally, these disorders are associated with poor outcome. Early diagnosis, supportive therapy and specific measures addressing the derranged metabolic process are the gold standards for favorable results. This review highlights treatment strategies for Inborn Errors of Metabolism (IEM) presenting in the neonatal period. PMID:27493313

Maternal obesity disrupts circadian rhythms of clock and metabolic genes in the offspring heart and liver.

PubMed

Wang, Danfeng; Chen, Siyu; Liu, Mei; Liu, Chang

2015-06-01

Early life nutritional adversity is tightly associated with the development of long-term metabolic disorders. Particularly, maternal obesity and high-fat diets cause high risk of obesity in the offspring. Those offspring are also prone to develop hyperinsulinemia, hepatic steatosis and cardiovascular diseases. However, the precise underlying mechanisms leading to these metabolic dysregulation in the offspring remain unclear. On the other hand, disruptions of diurnal circadian rhythms are known to impair metabolic homeostasis in various tissues including the heart and liver. Therefore, we investigated that whether maternal obesity perturbs the circadian expression rhythms of clock, metabolic and inflammatory genes in offspring heart and liver by using RT-qPCR and Western blotting analysis. Offspring from lean and obese dams were examined on postnatal day 17 and 35, when pups were nursed by their mothers or took food independently. On P17, genes examined in the heart either showed anti-phase oscillations (Cpt1b, Pparα, Per2) or had greater oscillation amplitudes (Bmal1, Tnf-α, Il-6). Such phase abnormalities of these genes were improved on P35, while defects in amplitudes still existed. In the liver of 17-day-old pups exposed to maternal obesity, the oscillation amplitudes of most rhythmic genes examined (except Bmal1) were strongly suppressed. On P35, the oscillations of circadian and inflammatory genes became more robust in the liver, while metabolic genes were still kept non-rhythmic. Maternal obesity also had a profound influence in the protein expression levels of examined genes in offspring heart and liver. Our observations indicate that the circadian clock undergoes nutritional programing, which may contribute to the alternations in energy metabolism associated with the development of metabolic disorders in early life and adulthood.

Olfaction Under Metabolic Influences

PubMed Central

2012-01-01

Recently published work and emerging research efforts have suggested that the olfactory system is intimately linked with the endocrine systems that regulate or modify energy balance. Although much attention has been focused on the parallels between taste transduction and neuroendocrine controls of digestion due to the novel discovery of taste receptors and molecular components shared by the tongue and gut, the equivalent body of knowledge that has accumulated for the olfactory system, has largely been overlooked. During regular cycles of food intake or disorders of endocrine function, olfaction is modulated in response to changing levels of various molecules, such as ghrelin, orexins, neuropeptide Y, insulin, leptin, and cholecystokinin. In view of the worldwide health concern regarding the rising incidence of diabetes, obesity, and related metabolic disorders, we present a comprehensive review that addresses the current knowledge of hormonal modulation of olfactory perception and how disruption of hormonal signaling in the olfactory system can affect energy homeostasis. PMID:22832483

The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper

PubMed Central

Gillberg, Christopher; Fernell, Elisabeth; Kočovská, Eva; Minnis, Helen; Bourgeron, Thomas; Thompson, Lucy

2017-01-01

Based on evidence from the relevant research literature, we present a hypothesis that there may be a link between cholesterol, vitamin D, and steroid hormones which subsequently impacts on the development of at least some of the “autisms” [Coleman & Gillberg]. Our hypothesis, driven by the peer reviewed literature, posits that there may be links between cholesterol metabolism, which we will refer to as “steroid metabolism” and findings of steroid abnormalities of various kinds (cortisol, testosterone, estrogens, progesterone, vitamin D) in autism spectrum disorder (ASD). Further research investigating these potential links is warranted to further our understanding of the biological mechanisms underlying ASD. Autism Res 2017. © 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. Autism Res 2017, 10: 1022–1044. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. PMID:28401679

Epigenetics of sleep and chronobiology.

PubMed

Qureshi, Irfan A; Mehler, Mark F

2014-03-01

The circadian clock choreographs fundamental biological rhythms. This system is comprised of the master circadian pacemaker in the suprachiasmatic nucleus and associated pacemakers in other tissues that coordinate complex physiological processes and behaviors, such as sleep, feeding, and metabolism. The molecular circuitry that underlies these clocks and orchestrates circadian gene expression has been the focus of intensive investigation, and it is becoming clear that epigenetic factors are highly integrated into these networks. In this review, we draw attention to the fundamental roles played by epigenetic mechanisms in transcriptional and post-transcriptional regulation within the circadian clock system. We also highlight how alterations in epigenetic factors and mechanisms are being linked with sleep-wake disorders. These observations provide important insights into the pathogenesis and potential treatment of these disorders and implicate epigenetic deregulation in the significant but poorly understood interconnections now emerging between circadian processes and neurodegeneration, metabolic diseases, cancer, and aging.

Management of female infertility from hormonal causes.

PubMed

Luciano, Antony A; Lanzone, Antonio; Goverde, Angelique J

2013-12-01

Hormonal causes of female infertility involve ovulatory dysfunctions that may result from dysfunction of the hypothalamic-pituitary-ovarian axis, peripheral endocrine glands, nonendocrine organs, or metabolic disorders. It is important to think of anovulation not as a diagnosis but as a symptom of a metabolic or endocrine disorder that requires a thorough diagnostic evaluation to identify the specific cause and to implement effective therapies that assure the best possible pregnancy outcome and avoid long-term adverse health consequences. In most instances, the medical history points to the underlying dysfunction, which can usually be confirmed with laboratory or imaging tests. For more challenging cases, more extensive evaluations may be needed, including perturbation studies. Nevertheless, the management of anovulatory infertility is gratifying because its causes are often manifest and the treatment usually results in resumption of ovulatory cycles, restoration of fertility, and healthy offspring through natural conception without requiring expensive and intrusive assisted reproductive technologies. © 2013.

Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias

PubMed Central

Imperlini, Esther; Santorelli, Lucia; Orrù, Stefania; Scolamiero, Emanuela; Ruoppolo, Margherita

2016-01-01

Organic acidemias (OAs) are inherited metabolic disorders caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders result in the accumulation of mono-, di-, or tricarboxylic acids, generally referred to as organic acids. The OA outcomes can involve different organs and/or systems. Some OA disorders are easily managed if promptly diagnosed and treated, whereas, in others cases, such as propionate metabolism-related OAs (propionic acidemia, PA; methylmalonic acidemia, MMA), neither diet, vitamin therapy, nor liver transplantation appears to prevent multiorgan impairment. Here, we review the recent developments in dissecting molecular bases of OAs by using integration of mass spectrometry- (MS-) based metabolomic and proteomic strategies. MS-based techniques have facilitated the rapid and economical evaluation of a broad spectrum of metabolites in various body fluids, also collected in small samples, like dried blood spots. This approach has enabled the timely diagnosis of OAs, thereby facilitating early therapeutic intervention. Besides providing an overview of MS-based approaches most frequently used to study the molecular mechanisms underlying OA pathophysiology, we discuss the principal challenges of metabolomic and proteomic applications to OAs. PMID:27403441

Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics

PubMed Central

Bravo, Roberto; Gutierrez, Tomás; Paredes, Felipe; Gatica, Damián; Rodriguez, Andrea E.; Pedrozo, Zully; Chiong, Mario; Parra, Valentina; Quest, Andrew F.G.; Rothermel, Beverly A.; Lavandero, Sergio

2014-01-01

Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER–mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID:22064245

Beneficial Effects of Cinnamon on the Metabolic Syndrome, Inflammation, and Pain, and Mechanisms Underlying These Effects – A Review

PubMed Central

Shen, Yan; Jia, Liu-Nan; Honma, Natsumi; Hosono, Takashi; Ariga, Toyohiko; Seki, Taiichiro

2012-01-01

Cinnamon is one of the most important herbal drugs and has been widely used in Asia for more than 4000 years. As a folk medicine, cinnamon has been traditionally applied to the treatment of inflammatory disorders and gastric diseases. After chemical profiling of cinnamon's components, their biological activities including antimicrobial, antiviral, antioxidant, antitumor, antihypertension, antilipemic, antidiabetes, gastroprotective and immunomodulatory were reported by many investigators. As a result, current studies have been performed mostly focusing on the bioactivity of cinnamon toward the recently generalized metabolic syndrome involving diabetes. In this review article, we provide an overview of the recent literature describing cinnamon's potential for preventing the metabolic syndrome. PMID:24716111

Acquired pendular nystagmus.

PubMed

Kang, Sarah; Shaikh, Aasef G

2017-04-15

Acquired pendular nystagmus is comprised of quasi-sinusoidal oscillations of the eyes significantly affecting gaze holding and clarity of vision. The most common causes of acquired pendular nystagmus include demyelinating disorders such as multiple sclerosis and the syndrome of ocular palatal tremor. However, several other deficits, such as pharmacological intoxication, metabolic and genetic disorders, and granulomatous disorders can lead to syndromes mimicking acquired pendular nystagmus. Study of the kinematic features of acquired pendular nystagmus has suggested a putative pathophysiology of an otherwise mysterious neurological disorder. Here we review clinical features of neurological deficits that co-occur with acquired pendular nystagmus. Subsequent discussion of the pathophysiology of individual forms of pendular nystagmus speculates on mechanisms of the underlying disease while providing insights into pharmacotherapy of nystagmus. Copyright © 2017 Elsevier B.V. All rights reserved.

Current concepts in the management of hidradenitis suppurativa in children.

PubMed

Danby, F William

2015-08-01

This review is intended to provide the background aetiopathogenetic framework upon which management of this disorder can be based, particularly with relation to new concepts of the pathogenesis of the disorder. The emphasis is on the prevention of the disorder's full expression by addressing the metabolic changes that drive the underlying structural damage and the immune system's subsequent reaction to this damage. The mechanism by which dietary factors impact on this disease are elucidated, the anatomic defect suspected to be responsible for the disorder is introduced, and an updated flow sheet describing and linking the clinicopathological changes recently described are provided. Recent work in the understanding of the induction and evolution of the lesions provides a background upon which the preventive regimen and both the medical and surgical approaches can be effectively based.

Natural molecules for the therapy of hyperandrogenism and metabolic disorders in PCOS.

PubMed

Cappelli, V; Musacchio, M C; Bulfoni, A; Morgante, G; De Leo, V

2017-06-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of women of reproductive age and a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology. However, PCOS is also associated with other metabolic abnormalities such as insulin resistance, impaired glucose tolerance, and diabetes. There are few medications that are approved for the most common symptoms of PCOS, leading to the off-label use of medications that were approved for other indications. One of the most common medications being used off label for PCOS is metformin. Research of other effective therapeutic options has included the utility of inositol. A systematic literature search of PubMed was performed using the following combination of terms: 'PCOS', 'hyperandrogenism' 'inositol', 'natural molecules'. Only papers published between 2000 and 2016 were included in our analysis. The present review analyzes all aspects of the choice of natural molecules in the treatment of hyperandrogenism and metabolic disorders in PCOS women. The rationale underlying the use of inositols as a therapeutic application in PCOS derives from their activities as insulin mimetic agents and their salutary effects on metabolism and hyperandrogenism without side effects. In this review will discuss the role of a number of natural associations between inositol and different substances in the treatment of hyperandrogenic symptoms in PCOS women.

Heparanase augments insulin receptor signaling in breast carcinoma

PubMed Central

Goldberg, Rachel; Sonnenblick, Amir; Hermano, Esther; Hamburger, Tamar; Meirovitz, Amichay; Peretz, Tamar; Elkin, Michael

2017-01-01

Recently, growing interest in the potential link between metabolic disorders (i.e., diabetes, obesity, metabolic syndrome) and breast cancer has mounted, including studies which indicate that diabetic/hyperinsulinemic women have a significantly higher risk of bearing breast tumors that are more aggressive and associated with higher death rates. Insulin signaling is regarded as a major contributor to this phenomenon; much less is known about the role of heparan sulfate-degrading enzyme heparanase in the link between metabolic disorders and cancer. In the present study we analyzed clinical samples of breast carcinoma derived from diabetic/non-diabetic patients, and investigated effects of heparanase on insulin signaling in breast carcinoma cell lines, as well as insulin-driven growth of breast tumor cells. We demonstrate that heparanase activity leads to enhanced insulin signaling and activation of downstream tumor-promoting pathways in breast carcinoma cells. In agreement, heparanase enhances insulin-induced proliferation of breast tumor cells in vitro. Moreover, analyzing clinical data from diabetic breast carcinoma patients, we found that concurrent presence of both diabetic state and heparanase in tumor tissue (as opposed to either condition alone) was associated with more aggressive phenotype of breast tumors in the patient cohort analyzed in our study (two-sided Fisher's exact test; p=0.04). Our findings highlight the emerging role of heparanase in powering effect of hyperinsulinemic state on breast tumorigenesis and imply that heparanase targeting, which is now under intensive development/clinical testing, could be particularly efficient in a growing fraction of breast carcinoma patients suffering from metabolic disorders. PMID:28038446

Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats.

PubMed

Gaspar, Renato Simões; Benevides, Renata Ohana Alves; Fontelles, João Lucas de Lima; Vale, Caroline Castro; França, Lucas Martins; Barros, Paulo de Tarso Silva; Paes, Antonio Marcus de Andrade

2016-05-01

Obesity and metabolic syndrome are the common causes of reproductive and fertility disorders in women. In particular, polycystic ovary syndrome, which is clinically characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, has been increasingly associated with metabolic disorders. However, given the broad interplay between metabolic and reproductive functions, this remains a field of intense research. In this study, we investigated the effect of monosodium l-glutamate (MSG)-induced obesity on reproductive biology of female rats. Newborn female rats were subcutaneously injected with MSG (4g/kg/day) or equiosmolar saline (CTR) each 2 days up to postnatal day (pnd) 10. On pnd 60, estrous cycle was evaluated using vaginal smears twice a day for 15 days, which showed MSG rats to be oligocyclic. Thereafter, animals were killed on estrous phase for blood and tissue collection. MSG rats had increased body mass, accumulation of retroperitoneal and visceral fat pads, and visceral adipocyte hypertrophy compared with CTR rats. MSG rats were also dyslipidemic and hyperinsulinemic but were normoglycemic and normoandrogenic. Ovarian morphology analysis showed that MSG rats had a two-fold decrease in oocyte count but a six-fold increase on ovarian follicular cysts, along with a higher number of total primordial and atretic follicles. Moreover, MSG rats had a four-fold increase in anti-Müllerian hormone immunohistochemical staining on antral follicles. Taken together, data presented here characterize MSG obesity as a unique model to study the metabolic pathways underlying reproductive disorders in the absence of overactivated hypothalamic-pituitary-gonadal axis. © 2016 Society for Endocrinology.

Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives.

PubMed

Groen, Robin N; de Clercq, Nicolien C; Nieuwdorp, Max; Hoenders, H J Rogier; Groen, Albert K

2018-06-01

Psychiatric disorders are often associated with metabolic comorbidities. However, the mechanisms through which metabolic and psychiatric disorders are connected remain unclear. Pre-clinical studies in rodents indicate that the bidirectional signaling between the intestine and the brain, the so-called microbiome-gut-brain axis, plays an important role in the regulation of both metabolism and behavior. The gut microbiome produces a vast number of metabolites that may be transported into the host and play a part in homeostatic control of metabolism as well as brain function. In addition to short chain fatty acids, many of these metabolites have been identified in recent years. To what extent both microbiota and their products control human metabolism and behavior is a subject of intense investigation. In this review, we will discuss the most recent findings concerning alterations in the gut microbiota as a possible pathophysiological factor for the co-occurrence of metabolic comorbidities in psychiatric disorders.

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

PubMed

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

2014-09-01

Women with polycystic ovary syndrome (PCOS) are at high risk for metabolic disorders, which prompted the American Association of Clinical Endocrinologists (AACE) to publish a 2005 position statement recommending screening for metabolic disease.The purposes of the present study were to 1) to examine changes in screening rates for obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), hyperlipidemia (HL), nonalcoholic fatty liver disease (NAFLD), and hypertension (HTN) in women with PCOS after publication of the 2005 AACE position statement and 2) to determine if screening rates and metabolic disorders vary by race-ethnicity. PCOS cases in 2006 (n = 547) and 2011 (n = 1,159) and metabolic disorders were identified by International Classification of Diseases, 9th revision (ICD9) code. Screening rates for metabolic disorders were determined by the presence of blood tests (hemoglobin A1c [HbA1c], lipid profile, alanine aminotransferase/aspartate aminotransferase [ALT/AST]). In 2006, ≤25% of PCOS patients underwent recommended screening tests: HbA1c 18%; lipid profile <20%; ALT/AST ≤25%. By 2011, only HbA1c testing had increased (18% to 21%). Obesity increased from 35% to 40%, while other metabolic disorders remained stable. Black women had the highest rates of obesity and HTN in 2011 (Obesity: Black 48%, Hispanic 44%, White 33%, Other 31%, P<.0001; HTN: Black 18%, Hispanic 9%, White 10%, Other 7%, P<.0001). Blacks and Hispanics were screened more often with ALT/AST testing (Black 27/27%, Hispanic 28/27%, White 23/22%, Other 17/18%, P = .02/.03). Screening rates were higher in the endocrine clinic for all metabolic disorders than in other clinics (P<.05). Despite the publication of recommendations in 2005, screening rates for metabolic disease in women with PCOS remained low across all race-ethnicities in 2011.

Adiposopathy, metabolic syndrome, quantum physics, general relativity, chaos and the Theory of Everything.

PubMed

Bays, Harold

2005-05-01

Excessive fat (adiposity) and dysfunctional fat (adiposopathy) constitute the most common worldwide epidemics of our time -- and perhaps of all time. Ongoing efforts to explain how the micro (adipocyte) and macro (body organ) biologic systems interact through function and dysfunction in promoting Type 2 diabetes mellitus, hypertension and dyslipidemia are not unlike the mechanistic and philosophical thinking processes involved in reconciling the micro (quantum physics) and macro (general relativity) theories in physics. Currently, the term metabolic syndrome refers to a constellation of consequences often associated with excess body fat and is an attempt to unify the associations known to exist between the four fundamental metabolic diseases of obesity, hyperglycemia (including Type 2 diabetes mellitus), hypertension and dyslipidemia. However, the association of adiposity with these metabolic disorders is not absolute and the metabolic syndrome does not describe underlying causality, nor does the metabolic syndrome necessarily reflect any reasonably related pathophysiologic process. Just as with quantum physics, general relativity and the four fundamental forces of the universe, the lack of an adequate unifying theory of micro causality and macro consequence is unsatisfying, and in medicine, impairs the development of agents that may globally improve both obesity and obesity-related metabolic disease. Emerging scientific and clinical evidence strongly supports the novel concept that it is not adiposity alone, but rather it is adiposopathy that is the underlying cause of most cases of Type 2 diabetes mellitus, hypertension and dyslipidemia. Adiposopathy is a plausible Theory of Everything for mankind's greatest metabolic epidemics.

Metabolic myopathies

NASA Technical Reports Server (NTRS)

Martin, A.; Haller, R. G.; Barohn, R.; Blomqvist, C. G. (Principal Investigator)

1994-01-01

Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise.

Diagnosis of Disorders of Iron Metabolism in Dogs and Cats.

PubMed

Bohn, Andrea A

2015-09-01

Iron is an essential element and is used by every cell in the body. This article summarizes iron metabolism and disorders associated with iron metabolism in dogs and cats. The diagnostic tests currently in use for assessing iron status are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Inflammatory and Metabolic Dysregulation and the 2-Year Course of Depressive Disorders in Antidepressant Users

PubMed Central

Vogelzangs, Nicole; Beekman, Aartjan TF; van Reedt Dortland, Arianne KB; Schoevers, Robert A; Giltay, Erik J; de Jonge, Peter; Penninx, Brenda WJH

2014-01-01

Scarce evidence suggests that inflammatory and metabolic dysregulation predicts poor response to antidepressants, which could result in worse depression outcome. This study prospectively examined whether inflammatory and metabolic dysregulation predicted the 2-year course of depressive disorders among antidepressant users. Data were from the Netherlands Study of Depression and Anxiety, including 315 persons (18–65 years) with a current depressive disorder (major depressive disorder, dysthymia) at baseline according to the DSM-IV criteria and using antidepressants. Inflammatory (C-reactive protein, interleukin-6 (IL-6), tumor-necrosis factor-α) and metabolic (waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, fasting glucose) factors were measured at baseline. Primary outcome for course of depression was indicated by whether or not a DSM-IV depressive disorder diagnosis was still/again present at 2-year follow-up, indicating chronicity of depression. Elevated IL-6, low HDL cholesterol, hypertriglyceridemia, and hyperglycemia were associated with chronicity of depression in antidepressant users. Persons showing ⩾4 inflammatory or metabolic dysregulations had a 1.90 increased odds of depression chronicity (95% CI=1.12–3.23). Among persons who recently (ie, at most 3 months) started antidepressant medication (N=103), having ⩾4 dysregulations was associated with a 6.85 increased odds of depression chronicity (95% CI=1.95–24.06). In conclusion, inflammatory and metabolic dysregulations were found to predict a more chronic course of depressive disorders among patients using antidepressants. This could suggest that inflammatory and metabolic dysregulation worsens depression course owing to reduced antidepressant treatment response and that alternative intervention treatments may be needed for depressed persons with inflammatory and metabolic dysregulation. PMID:24442097

Microglia energy metabolism in metabolic disorder.

PubMed

Kalsbeek, Martin J T; Mulder, Laurie; Yi, Chun-Xia

2016-12-15

Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx. Fatty acids are another source of energy for microglia and have also been shown to strongly influence microglial immune activity. Glutamine, although possibly suitable for use as an energy substrate by microglia, has been shown to have neurotoxic effects when overloaded. Microglial fuel metabolism might be associated with microglial reactivity under different pathophysiological conditions and a microglial fuel switch may thus be the underlying cause of hypothalamic dysregulation, which is associated with obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Scientific activities of the Department of Skin and Venereal Diseases of the Kharkov Medical Institute during 1966--1971 (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zadorozhnyi, B.

1973-04-01

Investigations include radiation lesions of the skin, some aspects of the pathogenesis of psoriasis, as well as other important problems of dermatology and venereology. Data of numerous studies are presented on morphological lesions, on disorders in the physiological functions and metabolic processes in the skin and internal organs under the effect of ionizing radiation and under a combined . effect of radiation and temperature. In patients with psoriasis, the concentration of free radicals was studied by the method of electronic paramagnetic resonance, as well as protein metabolism, the kinine system, the enzymatic metabolism in the skin and blood serum, themore » functional status of the liver and the kidneys. Materials are presented on the study of dermatitis and eczema in workers of the machine-building industry with reference to the social- hygienic and economic factors. New therapeutic ointment bases (aminobenthonites) were studied. Original studies are dedicated to important problems of venereology. (auth)« less

Alterations in Gut Microbiota and Immunity by Dietary Fat.

PubMed

Yang, Bo Gie; Hur, Kyu Yeon; Lee, Myung Shik

2017-11-01

Gut microbiota play critical physiological roles in energy extraction from the intestine and in the control of systemic immunity, as well as local intestinal immunity. Disturbance of gut microbiota leads to the development of several diseases, such as colitis, inflammatory bowel diseases, metabolic disorders, cancer, etc. From a metabolic point of view, the gut is a large metabolic organ and one of the first to come into contact with dietary fats. Interestingly, excessive dietary fat has been incriminated as a primary culprit of metabolic syndrome and obesity. After intake of high-fat diet or Western diet, extensive changes in gut microbiota have been observed, which may be an underlying cause of alterations in whole body metabolism and nutrient homeostasis. Here, we summarize recent data on changes in the gut microbiota and immunity associated with dietary fat, as well as their relationships with the pathogenesis of metabolic syndrome. These findings may provide insight into the understanding of the complex pathophysiology related to the development of metabolic diseases and offer an opportunity to develop novel candidates for therapeutic agents. © Copyright: Yonsei University College of Medicine 2017.

Correlated FLIM and PLIM for cell metabolism

NASA Astrophysics Data System (ADS)

Rück, A.; Breymayer, J.; Kalinina, S.

2016-03-01

Correlated imaging of phosphorescence and fluorescence lifetime parameters of metabolic markers is a challenge for direct investigating mechanisms related to cell metabolism and oxygen tension. A large variety of clinical phenotypes is associated with mitochondrial defects accomplished with changes in cell metabolism. In many cases the hypoxic microenvironment of cancer cells shifts metabolism from oxidative phosphorylation (OXPHOS) to anaerobic or aerobic glycolysis, a process known as "Warburg" effect. Also during stem cell differentiation a switch in cell metabolism is observed. A defective mitochondrial function associated with hypoxia has been invoked in many complex disorders such as type 2 diabetes, Alzheimers disease, cardiac ischemia/reperfusion injury, tissue inflammation and cancer. Cellular responses to oxygen tension have been studied extensively, optical imaging techniques based on time correlated single photon counting (TCSPC) to detect the underlying metabolic mechanisms are therefore of prominent interest. They offer the possibility by inspecting fluorescence decay characteristics of intrinsic coenzymes to directly image metabolic pathways. Moreover oxygen tension can be determined by considering the phosphorescence lifetime of a phosphorescent probe. The combination of both fluorescence lifetime imaging (FLIM) of coenzymes like NADH and FAD and phosphorescence lifetime (PLIM) of phosphorescent dyes could provide valuable information about correlation of metabolic pathways and oxygen tension.

Endocrine and metabolic disorders associated with human immune deficiency virus infection.

PubMed

Unachukwu, C N; Uchenna, D I; Young, E E

2009-01-01

Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

Ghrelin-Derived Peptides: A Link between Appetite/Reward, GH Axis, and Psychiatric Disorders?

PubMed Central

Labarthe, Alexandra; Fiquet, Oriane; Hassouna, Rim; Zizzari, Philippe; Lanfumey, Laurence; Ramoz, Nicolas; Grouselle, Dominique; Epelbaum, Jacques; Tolle, Virginie

2014-01-01

Psychiatric disorders are often associated with metabolic and hormonal alterations, including obesity, diabetes, metabolic syndrome as well as modifications in several biological rhythms including appetite, stress, sleep–wake cycles, and secretion of their corresponding endocrine regulators. Among the gastrointestinal hormones that regulate appetite and adapt the metabolism in response to nutritional, hedonic, and emotional dysfunctions, at the interface between endocrine, metabolic, and psychiatric disorders, ghrelin plays a unique role as the only one increasing appetite. The secretion of ghrelin is altered in several psychiatric disorders (anorexia, schizophrenia) as well as in metabolic disorders (obesity) and in animal models in response to emotional triggers (psychological stress …) but the relationship between these modifications and the physiopathology of psychiatric disorders remains unclear. Recently, a large literature showed that this key metabolic/endocrine regulator is involved in stress and reward-oriented behaviors and regulates anxiety and mood. In addition, preproghrelin is a complex prohormone but the roles of the other ghrelin-derived peptides, thought to act as functional ghrelin antagonists, are largely unknown. Altered ghrelin secretion and/or signaling in psychiatric diseases are thought to participate in altered appetite, hedonic response and reward. Whether this can contribute to the mechanism responsible for the development of the disease or can help to minimize some symptoms associated with these psychiatric disorders is discussed in the present review. We will thus describe (1) the biological actions of ghrelin and ghrelin-derived peptides on food and drugs reward, anxiety and depression, and the physiological consequences of ghrelin invalidation on these parameters, (2) how ghrelin and ghrelin-derived peptides are regulated in animal models of psychiatric diseases and in human psychiatric disorders in relation with the GH axis. PMID:25386163

Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders

PubMed Central

Burrage, Lindsay C.; Nagamani, Sandesh C.S.; Campeau, Philippe M.; Lee, Brendan H.

2014-01-01

Branched-chain amino acid (BCAA) metabolism plays a central role in the pathophysiology of both rare inborn errors of metabolism and the more common multifactorial diseases. Although deficiency of the branched-chain ketoacid dehydrogenase (BCKDC) and associated elevations in the BCAAs and their ketoacids have been recognized as the cause of maple syrup urine disease (MSUD) for decades, treatment options for this disorder have been limited to dietary interventions. In recent years, the discovery of improved leucine tolerance after liver transplantation has resulted in a new therapeutic strategy for this disorder. Likewise, targeting the regulation of the BCKDC activity may be an alternative potential treatment strategy for MSUD. The regulation of the BCKDC by the branched-chain ketoacid dehydrogenase kinase has also been implicated in a new inborn error of metabolism characterized by autism, intellectual disability and seizures. Finally, there is a growing body of literature implicating BCAA metabolism in more common disorders such as the metabolic syndrome, cancer and hepatic disease. This review surveys the knowledge acquired on the topic over the past 50 years and focuses on recent developments in the field of BCAA metabolism. PMID:24651065

Associations of metabolic disorder factors with the risk of uncontrolled hypertension: a follow-up cohort in rural China.

PubMed

Xiao, Jing; Hua, Tianqi; Shen, Huan; Zhang, Min; Wang, Xiao-Jian; Gao, Yue-Xia; Lu, Qinyun; Wu, Chuanli

2017-04-07

We evaluated how metabolic disorders affected antihypertension therapy. 2,912 rural Chinese patients with hypertension who provided blood samples, demographic and clinical data at baseline and after 1 year of antihypertension therapy were evaluated. At baseline, 1,515 patients (52.0%) were already receiving drug therapy and 11.4% of them had controlled blood pressure (BP). After 1 year, all 2,912 patients were receiving antihypertension therapy that was administered by community physicians, and 59.42% of them had controlled BP. Central obesity and abnormal triglyceride, high-density lipoprotein cholesterol, and glucose were associated with 15-70% higher risks of uncontrolled hypertension. Metabolic syndrome using the JIS criteria was associated with poor BP control (odds ratio: 1.71 and 1.54 for the baseline and follow-up datasets, respectively). The risk of uncontrolled hypertension increased with the number of metabolic disorders (p for trend <0.01). The presence of ≥3 metabolic disorder factors was associated with higher risks of poor BP control. The associations of metabolic factors and uncontrolled hypertension were stronger for the standard and modified ATP III criteria, compared to the IDF and JIS criteria. Metabolic factors were associated with less effective antihypertension therapy, and all definitions of metabolic syndrome helped identify patients with elevated risks of uncontrolled hypertension.

[Aging and homeostasis. Management of disorders in bone and calcium metabolism associated with ageing.

PubMed

Takeuchi, Yasuhiro

Disorders in bone and calcium metabolism associated with aging are based on secondary hyperparathyroidism due to impaired intestinal calcium absorption caused by insufficient vitamin D actions and augmented bone resorption due to sex hormone deficiency. Both of them are involved in the development of osteoporosis that increases risk of fractures. Therefore, the most important thing for management of disorders in bone and calcium metabolism associated with aging is to prevent fractures with appropriate drugs for osteoporosis.

Disorders of bone and bone mineral metabolism.

PubMed

Komoroski, Monica; Azad, Nasrin; Camacho, Pauline

2014-01-01

Metabolic bone disorders are very common in the general population and untreated, they can cause a variety of neurologic symptoms. These diseases include osteoporosis, vitamin D deficiency, Paget's disease, and alterations in calcium, phosphorus, and magnesium metabolism. Diagnosis is made through analysis of metabolic bone blood chemistries as well as radiologic studies such as dual energy X-ray absorptiometry (DXA) scans, bone scans, and X-rays. Treatment options have advanced significantly in the past decade for osteoporosis and Paget's disease and mainly include antiresorptive therapy. New recommendations for treatment of primary hyperparathyroidism are discussed as well as therapy for calcium, phosphorus, and mineral disorders. © 2014 Elsevier B.V. All rights reserved.

Effect of cytokine antibodies in the immunomodulation of inflammatory response and metabolic disorders induced by scorpion venom.

PubMed

Taibi-Djennah, Zahida; Laraba-Djebari, Fatima

2015-07-01

Androctonus australis hector (Aah) venom and its neurotoxins may affect the neuro-endocrine immunological axis due to their binding to ionic channels of axonal membranes. This binding leads to the release of neurotransmitters and immunological mediators accompanied by pathophysiological effects. Although the hyperglycemia induced by scorpion venom is clearly established, the involved mediators in these deregulations are unknown. The strong relationship between inflammation and the wide variety of physiological processes can suggest that the activation of the inflammatory response and the massive release of IL-6 and TNF-α release induced by the venom may induce hyperglycemia and various biological disorders. We therefore investigated in this study the contribution of IL-6 and TNF-α in the modulation of inflammatory response and metabolic disorder induced by Aah venom. Obtained results revealed that Aah venom induced inflammatory response characterized by significant increase of inflammatory cells in sera and tissues homogenates accompanied by hyperglycemia and hyperinsulinemia, suggesting that the venom induced insulin resistance. It also induced severe alterations in hepatic parenchyma associated to metabolic disorders and imbalanced redox status. Cytokine antagonists injected 30 min prior to Aah venom allowed a significant reduction of inflammatory biomarker and plasma glucose levels, they also prevented metabolic disorders, oxidative stress and hepatic tissue damage induced by Aah venom. In conclusion, IL-6 and TNF-α appear to play a crucial role in the inflammatory response, hyperglycemia and associated complications to glucose metabolism disorders (carbohydrate and fat metabolism disorders, oxidative stress and hepatic damage) observed following scorpion envenoming. Copyright © 2014 Elsevier B.V. All rights reserved.

Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder.

PubMed

McElroy, S L; Kemp, D E; Friedman, E S; Reilly-Harrington, N A; Sylvia, L G; Calabrese, J R; Rabideau, D J; Ketter, T A; Thase, M E; Singh, V; Tohen, M; Bowden, C L; Bernstein, E E; Brody, B D; Deckersbach, T; Kocsis, J H; Kinrys, G; Bobo, W V; Kamali, M; McInnis, M G; Leon, A C; Faraone, S; Nierenberg, A A; Shelton, R C

2015-06-26

Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tailoring Gut Microbiota for Enhanced Resilience and Performance Under Sleep-Deprived Conditions

DTIC Science & Technology

2016-08-01

psychological disorders, we have developed a hypothesis that sleep deprivation initially degrades the functional and structural integrity of the...obesity. Interestingly, perturbation of gut microbiota presents a pattern of metabolic abnormalities mirroring those induced by sleep deprivation. In...sleep deprivation initially causes degradation in the functional and structural integrity of the gastrointestinal tract. Data generated will be

Antioxidant metabolism and gene expression during ‘‘stain’’ development on ‘Fuji’ apples during cold storage

USDA-ARS?s Scientific Manuscript database

A distinct type of postharvest skin browning of apple fruit called ‘stain’ is a frequent disorder of ‘Fuji’ apples grown under high light conditions. Symptoms typically develop only on sun-exposed regions of the peel regardless of the presence of prior sun-related injury, but usually on the margins...

What Choline Metabolism Can Tell Us About the Underlying Mechanisms of Fetal Alcohol Spectrum Disorders

PubMed Central

2013-01-01

The consequences of fetal exposure to alcohol are very diverse and the likely molecular mechanisms involved must be able to explain how so many developmental processes could go awry. If pregnant rat dams are fed alcohol, their pups develop abnormalities characteristic of fetal alcohol spectrum disorders (FASD), but if these rat dams were also treated with choline, the effects from ethanol were attenuated in their pups. Choline is an essential nutrient in humans, and is an important methyl group donor. Alcohol exposure disturbs the metabolism of choline and other methyl donors. Availability of choline during gestation directly influences epigenetic marks on DNA and histones, and alters gene expression needed for normal neural and endothelial progenitor cell proliferation. Maternal diets low in choline alter development of the mouse hippocampus, and decrement memory for life. Women eating low-choline diets have an increased risk of having an infant with a neural tube or or ofacial cleft birth defect. Thus, the varied effects of choline could affect the expression of FASD, and studies on choline might shed some light on the underlying molecular mechanisms responsible for FASD. PMID:21259123

Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders.

PubMed

Yoo, Ji Youn; Kim, Sung Soo

2016-03-18

Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual's quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area.

Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders

PubMed Central

Yoo, Ji Youn; Kim, Sung Soo

2016-01-01

Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual’s quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area. PMID:26999199

Effect of apple polyphenol concentrate on lipid metabolism in rats under experimental insulin resistance.

PubMed

Zagayko, Andriy L; Kravchenko, Ganna B; Fylymonenko, Viktoriia P; Krasilnikova, Oksana A

Obesity is strongly associated with an increased risk of developing insulin resistance as the metabolic indicator of prediabetes and a major risk factor in diabetes mellitus type 2 pathogenesis. Medicinal products obtained from apples can be used as potent prophylactic and therapeutic remedies in treatment of diabetes mellitus. Experiment was designed to study the effect of total apple polyphenol food concentrate on lipid metabolism under experimental IR. Male Wistar rats weighting 180-210 g were used in the experiment. IR was induced by high-calorie diet enriched with fructose. The effect of total apple polyphenol food concentrate was compared with the action of epigallocatechin gallate and quercetin. To estimate the alterations in lipid metabolism in liver homogenate were measured triacylglycerols, free fatty acids, total phospholipids, TBA-reactive substance and conjugated dienes contents. In blood serum were measured total lipids, triacylglycerols, cholesterol, total phospholipids and reduced glutathione levels. The obtained results indicated that feeding rats with high-calorie diet enriched with fructose caused the dyslipidemia and oxidative stress development. The administration of quercetin, epigallocatechin gallate and total apple polyphenol food concentrate improved disorders of lipid metabolism and pro-oxidant-antioxidant homeostasis. Total apple polyphenol food concentrate had a more pronounced effect on studied indices that is probably due to synergism and additive effect of extract numerous components.

A Clinical Approach to the Diagnosis of Acid-Base Disorders

PubMed Central

Bear, Robert A.

1986-01-01

The ability to diagnose and manage acid-base disorders rapidly and effectively is essential to the care of critically ill patients. This article presents an approach to the diagnosis of pure and mixed acid-base disorders, metabolic or respiratory. The approach taken is based on using the law of mass-action equation as it applies to the bicarbonate buffer system (Henderson equation), using sub-classifications for diagnostic purposes of causes of metabolic acidosis and metabolic alkalosis, and using a knowledge of the well-defined and predictable compensatory responses that attempt to limit the change in pH in each of the primary acid-base disorders. PMID:21267134

MicroRNAs and lipoproteins: a connection beyond atherosclerosis?

PubMed Central

Norata, Giuseppe Danilo; Sala, Federica; Catapano, Alberico Luigi; Fernández-Hernando, Carlos

2014-01-01

MicroRNAs (miRNAs) are involved in the pathogenesis of a number of cardiovascular diseases. In this review article, we have summarized the role of miRNAs in regulating lipid metabolism and how their therapeutical inhibition may lead to new approaches to treat cardiometabolic diseases, including atherosclerosis and metabolic syndrome. Specific miRNAs, such as miR-33a and -33b, represent one of the most interesting and attractive targets for metabolic-related disorders and anti-miR33 approaches are under intensive investigation. In addition to miR-33, other miRNAs, including miR-122, are also emerging as key players in lipid metabolism. More recently miRNAs were shown to exert their activities in a paracrine manner and also systemically. The latter is possible due to lipid-carriers, including lipoproteins, that transport and protect miRNAs from degradation. The emerging strong connection between miRNAs, lipoproteins and lipid metabolism indicates the existence of a reciprocal modulation that might go beyond atherosclerosis. PMID:23260873

Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha as a Novel Target for Bipolar Disorder and Other Neuropsychiatric Disorders.

PubMed

Nierenberg, Andrew A; Ghaznavi, Sharmin A; Sande Mathias, Isadora; Ellard, Kristen K; Janos, Jessica A; Sylvia, Louisa G

2018-05-01

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions. The purpose of this article is to review the physiology of PGC-1 alpha, PPARs, and the role of PPAR agonists to target PGC-1 alpha to treat neurodegenerative diseases and bipolar disorder. We also review clinical trials of repurposed antidiabetic thiazolidines and anti-triglyceride fibrates (PPAR agonists) for neurodegenerative diseases and bipolar disorder. PGC-1 alpha and PPARs are innovative potential targets for bipolar disorder and warrant future clinical trials. Copyright © 2018. Published by Elsevier Inc.

Steroidogenic versus Metabolic Programming of Reproductive Neuroendocrine, Ovarian and Metabolic Dysfunctions.

PubMed

Cardoso, Rodolfo C; Puttabyatappa, Muraly; Padmanabhan, Vasantha

2015-01-01

The susceptibility of the reproductive system to early exposure to steroid hormones has become a major concern in our modern societies. Human fetuses are at risk of abnormal programming via exposure to endocrine disrupting chemicals, inadvertent use of contraceptive pills during pregnancy, as well as from excess exposure to steroids due to disease states. Animal models provide an unparalleled resource to understand the developmental origin of diseases. In female sheep, prenatal exposure to testosterone excess results in an array of adult reproductive disorders that recapitulate those seen in women with polycystic ovary syndrome (PCOS), including disrupted neuroendocrine feedback mechanisms, increased pituitary sensitivity to gonadotropin-releasing hormone, luteinizing hormone excess, functional hyperandrogenism, and multifollicular ovarian morphology culminating in early reproductive failure. Prenatal testosterone treatment also leads to fetal growth retardation, insulin resistance, and hypertension. Mounting evidence suggests that developmental exposure to an improper steroidal/metabolic environment may mediate the programming of adult disorders in prenatal testosterone-treated females, and these defects are maintained or amplified by the postnatal sex steroid and metabolic milieu. This review addresses the steroidal and metabolic contributions to the development and maintenance of the PCOS phenotype in the prenatal testosterone-treated sheep model, including the effects of prenatal and postnatal treatment with an androgen antagonist or insulin sensitizer as potential strategies to prevent/ameliorate these dysfunctions. Insights obtained from these intervention strategies on the mechanisms underlying these defects are likely to have translational relevance to human PCOS. © 2015 S. Karger AG, Basel.

[Clinical application of mass spectrometry in the pediatric field: current topics].

PubMed

Yamaguchi, Seiji

2013-09-01

Mass spectrometry, including tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), is becoming prominent in the diagnosis of metabolic disorders in the pediatric field. It enables biochemical diagnosis of metabolic disorders from the metabolic profiles obtained by MS/MS and/or GC/MS. In neonatal mass screening for inherited metabolic disease (IMD) using MS/MS, amino acids and acylcarnitines on dried blood spots are analyzed. The target diseases include amino acidemia, urea cycle disorder, organic acidemia, and fatty acid oxidation disorder. In the MS/MS screening, organic acid analysis using GC/MS is required for differential and/or definite diagnosis of the IMDs. GC/MS data processing, however, is difficult, and metabolic diagnosis often requires the necessary skills and expertize. We developed an automated system of GC/MS data processing and autodiagnosis, and the biochemical diagnosis using GC/MS became markedly easier and user-friendly. Mass spectrometric techniques will expand from research laboratories to clinical laboratories in the near future.

Is the Gut Microbiota a New Factor Contributing to Obesity and Its Metabolic Disorders?

PubMed Central

Harris, Kristina; Kassis, Amira; Major, Geneviève; Chou, Chieh J.

2012-01-01

The gut microbiota refers to the trillions of microorganisms residing in the intestine and is integral in multiple physiological processes of the host. Recent research has shown that gut bacteria play a role in metabolic disorders such as obesity, diabetes, and cardiovascular diseases. The mechanisms by which the gut microbiota affects metabolic diseases are by two major routes: (1) the innate immune response to the structural components of bacteria (e.g., lipopolysaccharide) resulting in inflammation and (2) bacterial metabolites of dietary compounds (e.g., SCFA from fiber), which have biological activities that regulate host functions. Gut microbiota has evolved with humans as a mutualistic partner, but dysbiosis in a form of altered gut metagenome and collected microbial activities, in combination with classic genetic and environmental factors, may promote the development of metabolic disorders. This paper reviews the available literature about the gut microbiota and aforementioned metabolic disorders and reveals the gaps in knowledge for future study. PMID:22315672

Disorders of fuel metabolism: medical complications associated with starvation, eating disorders, dietary fads, and supplements.

PubMed

Judge, Bryan S; Eisenga, Bernard H

2005-08-01

Disorders of fuel metabolism as they relate to abnormal fuel intake,abnormal fuel expenditure, and dietary supplements are the focus of this article. The emergency physician should be aware of the medical complications that can occur as a result of starvation states,eating disorders, fad diets, hypermetabolic states, and ergogenic aids. Knowledge and understanding of the complications associated with these disorders will facilitate the diagnosis and management of patients who present to the emergency department with any of the disorders reviewed.

A Continuum Model for Metabolic Gas Exchange in Pear Fruit

PubMed Central

Ho, Q. Tri; Verboven, Pieter; Verlinden, Bert E.; Lammertyn, Jeroen; Vandewalle, Stefan; Nicolaï, Bart M.

2008-01-01

Exchange of O2 and CO2 of plants with their environment is essential for metabolic processes such as photosynthesis and respiration. In some fruits such as pears, which are typically stored under a controlled atmosphere with reduced O2 and increased CO2 levels to extend their commercial storage life, anoxia may occur, eventually leading to physiological disorders. In this manuscript we have developed a mathematical model to predict the internal gas concentrations, including permeation, diffusion, and respiration and fermentation kinetics. Pear fruit has been selected as a case study. The model has been used to perform in silico experiments to evaluate the effect of, for example, fruit size or ambient gas concentration on internal O2 and CO2 levels. The model incorporates the actual shape of the fruit and was solved using fluid dynamics software. Environmental conditions such as temperature and gas composition have a large effect on the internal distribution of oxygen and carbon dioxide in fruit. Also, the fruit size has a considerable effect on local metabolic gas concentrations; hence, depending on the size, local anaerobic conditions may result, which eventually may lead to physiological disorders. The model developed in this manuscript is to our knowledge the most comprehensive model to date to simulate gas exchange in plant tissue. It can be used to evaluate the effect of environmental stresses on fruit via in silico experiments and may lead to commercial applications involving long-term storage of fruit under controlled atmospheres. PMID:18369422

Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

PubMed

Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Nakamura, Hiroyuki; Misaka, Ryoichi; Nagai, Atsushi; Aoshiba, Kazutetsu

2017-05-01

Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Metabolomic Analysis in Brain Research: Opportunities and Challenges

PubMed Central

Vasilopoulou, Catherine G.; Margarity, Marigoula; Klapa, Maria I.

2016-01-01

Metabolism being a fundamental part of molecular physiology, elucidating the structure and regulation of metabolic pathways is crucial for obtaining a comprehensive perspective of cellular function and understanding the underlying mechanisms of its dysfunction(s). Therefore, quantifying an accurate metabolic network activity map under various physiological conditions is among the major objectives of systems biology in the context of many biological applications. Especially for CNS, metabolic network activity analysis can substantially enhance our knowledge about the complex structure of the mammalian brain and the mechanisms of neurological disorders, leading to the design of effective therapeutic treatments. Metabolomics has emerged as the high-throughput quantitative analysis of the concentration profile of small molecular weight metabolites, which act as reactants and products in metabolic reactions and as regulatory molecules of proteins participating in many biological processes. Thus, the metabolic profile provides a metabolic activity fingerprint, through the simultaneous analysis of tens to hundreds of molecules of pathophysiological and pharmacological interest. The application of metabolomics is at its standardization phase in general, and the challenges for paving a standardized procedure are even more pronounced in brain studies. In this review, we support the value of metabolomics in brain research. Moreover, we demonstrate the challenges of designing and setting up a reliable brain metabolomic study, which, among other parameters, has to take into consideration the sex differentiation and the complexity of brain physiology manifested in its regional variation. We finally propose ways to overcome these challenges and design a study that produces reproducible and consistent results. PMID:27252656

Transcriptomic analysis of fruit stored under cold conditions using controlled atmosphere in Prunus persica cv. "Red Pearl".

PubMed

Sanhueza, Dayan; Vizoso, Paula; Balic, Iván; Campos-Vargas, Reinaldo; Meneses, Claudio

2015-01-01

Cold storage (CS) can induce a physiological disorder known as chilling injury (CI) in nectarine fruits. The main symptom is mealiness that is perceived as non-juicy fruit by consumers. Postharvest treatments such as controlled atmosphere (CA; a high CO2 concentration and low O2) have been used under cold conditions to avoid this disorder. With the objective of exploring the mechanisms involved in the CA effect on mealiness prevention, we analyzed transcriptomic changes under six conditions of "Red Pearl" nectarines by RNA-Seq. Our analysis included just harvested nectarines, juicy non-stored fruits, fruits affected for CI after CS and fruits stored in a combination of CA plus CS without CI phenotype. Nectarines stored in cold conditions combined with CA treatment resulted in less mealiness; we obtained 21.6% of juice content compared with just CS fruits (7.7%; mealy flesh). RNA-Seq data analyses were carried out to study the gene expression for different conditions assayed. During ripening, we detected that nectarines exposed to CA treatment expressed a similar number of genes compared with fruits that were not exposed to cold conditions. Firm fruits have more differentially expressed genes than soft fruits, which suggest that most important changes occur during CS. On the other hand, gene ontology analysis revealed enrichment mainly in metabolic and cellular processes. Differentially expressed genes analysis showed that low O2 concentrations combined with cold conditions slows the metabolic processes more than just the cold storage, resulting mainly in the suppression of primary metabolism and cold stress response. This is a significant step toward unraveling the molecular mechanism that explains the effectiveness of CA as a tool to prevent CI development on fruits.

Transcriptomic analysis of fruit stored under cold conditions using controlled atmosphere in Prunus persica cv. “Red Pearl”

PubMed Central

Sanhueza, Dayan; Vizoso, Paula; Balic, Iván; Campos-Vargas, Reinaldo; Meneses, Claudio

2015-01-01

Cold storage (CS) can induce a physiological disorder known as chilling injury (CI) in nectarine fruits. The main symptom is mealiness that is perceived as non-juicy fruit by consumers. Postharvest treatments such as controlled atmosphere (CA; a high CO2 concentration and low O2) have been used under cold conditions to avoid this disorder. With the objective of exploring the mechanisms involved in the CA effect on mealiness prevention, we analyzed transcriptomic changes under six conditions of “Red Pearl” nectarines by RNA-Seq. Our analysis included just harvested nectarines, juicy non-stored fruits, fruits affected for CI after CS and fruits stored in a combination of CA plus CS without CI phenotype. Nectarines stored in cold conditions combined with CA treatment resulted in less mealiness; we obtained 21.6% of juice content compared with just CS fruits (7.7%; mealy flesh). RNA-Seq data analyses were carried out to study the gene expression for different conditions assayed. During ripening, we detected that nectarines exposed to CA treatment expressed a similar number of genes compared with fruits that were not exposed to cold conditions. Firm fruits have more differentially expressed genes than soft fruits, which suggest that most important changes occur during CS. On the other hand, gene ontology analysis revealed enrichment mainly in metabolic and cellular processes. Differentially expressed genes analysis showed that low O2 concentrations combined with cold conditions slows the metabolic processes more than just the cold storage, resulting mainly in the suppression of primary metabolism and cold stress response. This is a significant step toward unraveling the molecular mechanism that explains the effectiveness of CA as a tool to prevent CI development on fruits. PMID:26483806

Diagnosis and treatment of simple acid-base disorders.

PubMed

Ayers, Phil; Warrington, Laurie

2008-01-01

The ability to diagnose and treat acid-base disorders is an important component in the practice of the nutrition support clinician. A complete understanding of the basic principles of metabolic and respiratory disorders allows the practitioner to formulate educated decisions regarding fluids, parenteral nutrition salts, and the management of electrolytes. This review will discuss the diagnosis and treatment of common metabolic and respiratory disorders encountered in nutrition support practice.

Platform for systems medicine research and diagnostic applications in psychotic disorders-The METSY project.

PubMed

Frank, Elisabeth; Maier, Dieter; Pajula, Juha; Suvitaival, Tommi; Borgan, Faith; Butz-Ostendorf, Markus; Fischer, Alexander; Hietala, Jarmo; Howes, Oliver; Hyötyläinen, Tuulia; Janssen, Joost; Laurikainen, Heikki; Moreno, Carmen; Suvisaari, Jaana; Van Gils, Mark; Orešič, Matej

2018-04-01

Psychotic disorders are associated with metabolic abnormalities including alterations in glucose and lipid metabolism. A major challenge in the treatment of psychosis is to identify patients with vulnerable metabolic profiles who may be at risk of developing cardiometabolic co-morbidities. It is established that both central and peripheral metabolic organs use lipids to control energy balance and regulate peripheral insulin sensitivity. The endocannabinoid system, implicated in the regulation of glucose and lipid metabolism, has been shown to be dysregulated in psychosis. It is currently unclear how these endocannabinoid abnormalities relate to metabolic changes in psychosis. Here we review recent research in the field of metabolic co-morbidities in psychotic disorders as well as the methods to study them and potential links to the endocannabinoid system. We also describe the bioinformatics platforms developed in the EU project METSY for the investigations of the biological etiology in patients at risk of psychosis and in first episode psychosis patients. The METSY project was established with the aim to identify and evaluate multi-modal peripheral and neuroimaging markers that may be able to predict the onset and prognosis of psychiatric and metabolic symptoms in patients at risk of developing psychosis and first episode psychosis patients. Given the intrinsic complexity and widespread role of lipid metabolism, a systems biology approach which combines molecular, structural and functional neuroimaging methods with detailed metabolic characterisation and multi-variate network analysis is essential in order to identify how lipid dysregulation may contribute to psychotic disorders. A decision support system, integrating clinical, neuropsychological and neuroimaging data, was also developed in order to aid clinical decision making in psychosis. Knowledge of common and specific mechanisms may aid the etiopathogenic understanding of psychotic and metabolic disorders, facilitate early disease detection, aid treatment selection and elucidate new targets for pharmacological treatments. Copyright © 2017. Published by Elsevier Masson SAS.

The Gut Microbiota and Autism Spectrum Disorders

PubMed Central

Li, Qinrui; Han, Ying; Dy, Angel Belle C.; Hagerman, Randi J.

2017-01-01

Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD. PMID:28503135

Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells

PubMed Central

Liu, Y; Cheng, H; Zhou, Y; Zhu, Y; Bian, R; Chen, Y; Li, C; Ma, Q; Zheng, Q; Zhang, Y; Jin, H; Wang, X; Chen, Q; Zhu, D

2013-01-01

Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells. PMID:23412387

The dysmetabolic syndrome: epidemiology and etiology.

PubMed

Sauerwein, H P

2006-01-01

The metabolic syndrome is a common metabolic disorder that results from the increasing prevalence of obesity. It also refers to a clustering of specific cardiovascular disease risk factors whose underlying pathophysiology is thought to be related to insulin resistance with an excessive flux of fatty acids implicated. Opinions have varied as to whether the metabolic syndrome should be defined to indicate mainly insulin resistance, the metabolic consequences of obesity, risk of cardiovascular disease, or simply a collection of statistically related factors. Based on these different viewpoints 4 definition sets of the metabolic syndrome are formulated. The pros and cons of each of them are extensively discussed. A major role in the etiology of the metabolic syndrome is ascribed to the occurrence of insulin resistance. Data are provided that insulin resistance can worsen the expression of this syndrome, but cannot have a primary role. Therefore, insulin resistance is not the main player of the metabolic syndrome, but central obesity is. Free fatty acid induced insulin resistance is found and induced by central obesity. The metabolic syndrome is a cluster of abnormalities in which each of them deserves its own (maximal) treatment to diminish the risk for cardiovascular disease.

Nuts and Dried Fruits: An Update of Their Beneficial Effects on Type 2 Diabetes

PubMed Central

Hernández-Alonso, Pablo; Camacho-Barcia, Lucía; Bulló, Mònica; Salas-Salvadó, Jordi

2017-01-01

Nuts and dried fruit are essential foods in the Mediterranean diet. Their frequent consumption has been associated with the prevention and/or the management of such metabolic conditions as type 2 diabetes (T2D), metabolic syndrome and cardiovascular diseases. Several previous reviews of epidemiological studies and clinical trials have evaluated the associations of nuts and/or dried fruit with various metabolic disorders. However, no reviews have focused on the mechanisms underlying the role of nuts and/or dried fruit in insulin resistance and T2D. This review aims to report nut and dried-fruit nutritional interventions in animals and humans, and to focus on mechanisms that could play a significant role in the prevention and treatment of insulin resistance and T2D. PMID:28657613

Nuts and Dried Fruits: An Update of Their Beneficial Effects on Type 2 Diabetes.

PubMed

Hernández-Alonso, Pablo; Camacho-Barcia, Lucía; Bulló, Mònica; Salas-Salvadó, Jordi

2017-06-28

Nuts and dried fruit are essential foods in the Mediterranean diet. Their frequent consumption has been associated with the prevention and/or the management of such metabolic conditions as type 2 diabetes (T2D), metabolic syndrome and cardiovascular diseases. Several previous reviews of epidemiological studies and clinical trials have evaluated the associations of nuts and/or dried fruit with various metabolic disorders. However, no reviews have focused on the mechanisms underlying the role of nuts and/or dried fruit in insulin resistance and T2D. This review aims to report nut and dried-fruit nutritional interventions in animals and humans, and to focus on mechanisms that could play a significant role in the prevention and treatment of insulin resistance and T2D.

Inborn Errors of Metabolism and Epilepsy: Current Understanding, Diagnosis, and Treatment Approaches

PubMed Central

Sharma, Suvasini; Prasad, Asuri N.

2017-01-01

Inborn errors of metabolism (IEM) are a rare cause of epilepsy, but seizures and epilepsy are frequently encountered in patients with IEM. Since these disorders are related to inherited enzyme deficiencies with resulting effects on metabolic/biochemical pathways, the term “metabolic epilepsy” can be used to include these conditions. These epilepsies can present across the life span, and share features of refractoriness to anti-epileptic drugs, and are often associated with co-morbid developmental delay/regression, intellectual, and behavioral impairments. Some of these disorders are amenable to specific treatment interventions; hence timely and appropriate diagnosis is critical to improve outcomes. In this review, we discuss those disorders in which epilepsy is a dominant feature and present an approach to the clinical recognition, diagnosis, and management of these disorders, with a greater focus on primarily treatable conditions. Finally, we propose a tiered approach that will permit a clinician to systematically investigate, identify, and treat these rare disorders. PMID:28671587

The proteome of methylmalonic acidemia (MMA): the elucidation of altered pathways in patient livers.

PubMed

Caterino, Marianna; Chandler, Randy J; Sloan, Jennifer L; Dorko, Kenneth; Cusmano-Ozog, Kristina; Ingenito, Laura; Strom, Stephen C; Imperlini, Esther; Scolamiero, Emanuela; Venditti, Charles P; Ruoppolo, Margherita

2016-02-01

Methylmalonic acidemia (MMA) is a heterogeneous and severe autosomal recessive inborn error of metabolism most commonly caused by the deficient activity of the vitamin B12 dependent enzyme, methylmalonyl-CoA mutase (MUT). The main treatment for MMA patients is the dietary restriction of propiogenic amino acids and carnitine supplementation. Despite treatment, the prognosis for vitamin B12 non-responsive patients remains poor and is associated with neonatal lethality, persistent morbidity and decreased life expectancy. While multi-organ pathology is a feature of MMA, the liver is severely impacted by mitochondrial dysfunction which likely underlies the metabolic instability experienced by the patients. Liver and/or combined liver/kidney transplantation is therefore sometimes performed in severely affected patients. Using liver specimens from donors and MMA patients undergoing elective liver transplantation collected under a dedicated natural history protocol (clinicaltrials.gov: NCT00078078), we employed proteomics to characterize the liver pathology and impaired hepatic metabolism observed in the patients. Pathway analysis revealed perturbations of enzymes involved in energy metabolism, gluconeogenesis and Krebs cycle anaplerosis. Our findings identify new pathophysiologic and therapeutic targets that could be valuable for designing alternative therapies to alleviate clinical manifestations seen in this disorder.

Maternal Obesity and Developmental Programming of Metabolic Disorders in Offspring: Evidence from Animal Models

PubMed Central

Li, M.; Sloboda, D. M.; Vickers, M. H.

2011-01-01

The incidence of obesity and overweight has reached epidemic proportions in the developed world as well as in those countries transitioning to first world economies, and this represents a major global health problem. Concern is rising over the rapid increases in childhood obesity and metabolic disease that will translate into later adult obesity. Although an obesogenic nutritional environment and increasingly sedentary lifestyle contribute to our risk of developing obesity, a growing body of evidence links early life nutritional adversity to the development of long-term metabolic disorders. In particular, the increasing prevalence of maternal obesity and excess maternal weight gain has been associated with a heightened risk of obesity development in offspring in addition to an increased risk of pregnancy-related complications. The mechanisms that link maternal obesity to obesity in offspring and the level of gene-environment interactions are not well understood, but the early life environment may represent a critical window for which intervention strategies could be developed to curb the current obesity epidemic. This paper will discuss the various animal models of maternal overnutrition and their importance in our understanding of the mechanisms underlying altered obesity risk in offspring. PMID:21969822

Metabolic myopathies: functional evaluation by different exercise testing approaches.

PubMed

Volpi, L; Ricci, G; Orsucci, D; Alessi, R; Bertolucci, F; Piazza, S; Simoncini, C; Mancuso, M; Siciliano, G

2011-08-01

Metabolic myopathies are a clinically and etiologically heterogeneous group of disorders due to defects in muscular energy metabolism. They include glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders. The typical manifestations of a metabolic myopathy are exercise-induced myalgias, exercise intolerance, and cramps. Evaluating subjects with such symptoms is not easy because of the frequent lack of clinical features. Exercise tests are, therefore, reliable screening tools. Here, we discuss the possible role of such exercise testing techniques in the diagnostic approach of a patient with suspected metabolic myopathy.

Psychosocial and metabolic function by smoking status in individuals with binge eating disorder and obesity.

PubMed

Udo, Tomoko; White, Marney A; Barnes, Rachel D; Ivezaj, Valentina; Morgan, Peter; Masheb, Robin M; Grilo, Carlos M

2016-02-01

Individuals with binge eating disorder (BED) report smoking to control appetite and weight. Smoking in BED is associated with increased risk for comorbid psychiatric disorders, but its impact on psychosocial functioning and metabolic function has not been evaluated. Participants were 429 treatment-seeking adults (72.4% women; mean age 46.2±11.0years old) with BED comorbid with obesity. Participants were categorized into current smokers (n=66), former smokers (n=145), and never smokers (n=218). Smoking status was unrelated to most historical eating/weight variables and to current eating disorder psychopathology. Smoking status was associated with psychiatric, psychosocial, and metabolic functioning. Compared with never smokers, current smokers were more likely to meet lifetime diagnostic criteria for alcohol (OR=5.51 [95% CI=2.46-12.33]) and substance use disorders (OR=7.05 [95% CI=3.37-14.72]), poorer current physical quality of life, and increased risk for metabolic syndrome (OR=1.80 [95% CI=0.97-3.35]) and related metabolic risks (reduced HDL, elevated total cholesterol). On the other hand, the odds of meeting criteria for lifetime psychiatric comorbidity or metabolic abnormalities were not significantly greater in former smokers, relative to never smokers. Our findings suggest the importance of promoting smoking cessation in treatment-seeking patients with BED and obesity for its potential long-term implications for psychiatric and metabolic functioning. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emerging Potential of Natural Products as an Alternative Strategy to Pharmacological Agents Used Against Metabolic Disorders.

PubMed

Dias, Tânia R; Bernardino, Raquel L; Meneses, Maria J; Sousa, Mário; Sá, Rosália; Alves, Marco G; Silva, Branca M; Oliveira, Pedro F

2016-01-01

Human metabolism is an essential biological process that involves the consumption of different substrates to ensure the nutritional and energetic needs of cells. The disruption of this highly regulated system constitutes the onset of several disorders/dysfunctions such as diabetes mellitus, cardiovascular diseases and hypertension. In this review, we propose to discuss promising natural products that can act as modulators of cell metabolism and point towards possible targets to take into account in the development of new therapies against metabolic diseases. After having defined our main focus, we undertook an intensive search of bibliographic databases to select the peer-reviewed papers that fits within the review thematic. The information of the screened papers was described in an organized manner through the review and different types of studies were included. Two hundred and seventy papers were included in the review, as well as one reliable website from the World Health Organization. Several articles described that pharmacological agents are commonly used to counteract metabolic disorders. However, in many cases these products are insufficient, represent high costs to health care systems and are associated with several undesirable effects, highlighting the need to search for new therapies. Notably, many papers reported the promising results of natural products in the treatment of several metabolic disorders, constituting a possible alternative or complementary strategy to pharmacological agents. The findings of this review confirm that the currently available treatments for metabolic disorders and its associated complications remain far below the expected results.

Thyroid function in adult Nigerians with metabolic syndrome.

PubMed

Udenze, Ifeoma; Nnaji, Ilochi; Oshodi, Temitope

2014-01-01

Metabolic syndrome and thyroid dysfunction are two common disorders encountered in the metabolic clinic. Recently, there has been increased interest in the association between the two disorders because of the similarities between symptoms of hypothyroidism and components of the metabolic syndrome. While some reports suggest that metabolic syndrome is associated with subclinical hypothyroidism, this concept is largely under investigated in Nigerian adults with metabolic syndrome. The aim of this study is to determine the thyroid function status of adult Nigerians with metabolic syndrome and determine the association, if any, between metabolic syndrome and thyroid function. This was a cross sectional study of one hundred and fifty adults, members of staff of the College of Medicine of the University of Lagos. The participants were recruited using a cluster random sampling method. The Ethical Research & Review Committee of the institution approved the study protocol and signed informed consent was obtained from the participants. The statistics was analysed using the IBM SPSS Software of version 19.0. The Student's t test, Chi square test and multivariate regression analysis were employed for the analysis. Statistical significance was set at p < 0.05. Thirty nine (twenty-six percent) of the study participants had metabolic syndrome and one hundred and eleven (seventy-four percent) of the study participants did not have metabolic syndrome, served as controls. Those who had metabolic syndrome group were significantly older (p = 0.03), metabolic syndrome was significantly associated with the female gender (p = 0.0002), higher systolic blood pressure (p = 0.0034), diastolic blood pressure (p = 0.0009), waist circumference (p < 0.0001), body mass index (p < 0.0001), waist-hip ratio (p = 0.003), fasting serum glucose (p = 0.0457) and free thyroxine (fT4) levels (p = 0.0496). Those with metabolic syndrome had significantly lower HDL (P = 0.004) and free triiodothyronine (fT3) levels (p = 0.037). There was no statistically significant difference in the thyroid stimulating hormone (TSH) levels between individuals with and without metabolic syndrome. Thirty-three percent of the metabolic syndrome cases had sick euthyroid syndrome (p= < 0.0001). In multivariate regression, waist circumference was significantly and inversely associated with the sick euthyroid syndrome (p = 0.011). Metabolic syndrome is associated with the sick euthyroid syndrome in adult Nigerians. Abdominal obesity appears to be the link between metabolic syndrome and the sick euthyroid syndrome.

Genetics Home Reference: glutamate formiminotransferase deficiency

MedlinePlus

... two steps in the breakdown (metabolism) of the amino acid histidine, a building block of most proteins. It ... 4 links) Encyclopedia: Megaloblastic Anemia (image) Health Topic: Amino Acid Metabolism Disorders Health Topic: Genetic Brain Disorders Health ...

Length of psychiatric hospitalization is correlated with CYP2D6 functional status in inpatients with major depressive disorder.

PubMed

Ruaño, Gualberto; Szarek, Bonnie L; Villagra, David; Gorowski, Krystyna; Kocherla, Mohan; Seip, Richard L; Goethe, John W; Schwartz, Harold I

2013-06-01

This study aimed to determine the effect of the CYP2D6 genotype on the length of hospitalization stay for patients treated for major depressive disorder. A total of 149 inpatients with a diagnosis of major depressive disorder at the Institute of Living, Hartford Hospital (CT, USA), were genotyped to detect altered alleles in the CYP2D6 gene. Prospectively defined drug metabolism indices (metabolic reserve, metabolic alteration and allele alteration) were determined quantitatively and assessed for their relationship to length of hospitalization stay. Hospital stay was significantly longer in deficient CYP2D6 metabolizers (metabolic reserve <2) compared with functional or suprafunctional metabolizers (metabolic reserve ≥2; 7.8 vs 5.7 days, respectively; p = 0.002). CYP2D6 enzymatic functional status significantly affected length of hospital stay, perhaps due to reduced efficacy or increased side effects of the medications metabolized by the CYP2D6 isoenzyme. Functional scoring of CYP2D6 alleles may have a substantial impact on the quality of care, patient satisfaction and the economics of psychiatric treatment.

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

PubMed Central

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

Peak hyperammonemia and atypical acute liver failure: The eruption of an urea cycle disorder during hyperemesis gravidarum.

PubMed

Weiss, Nicolas; Mochel, Fanny; Rudler, Marika; Demeret, Sophie; Lebray, Pascal; Conti, Filomena; Galanaud, Damien; Ottolenghi, Chris; Bonnefont, Jean-Paul; Dommergues, Marc; Bernuau, Jacques; Thabut, Dominique

2017-09-20

Inborn urea cycle disorders are under-recognised metabolic causes of hyperammonemia in adults. A 28-year-old primigravida, seven weeks pregnant, affected by hyperemesis gravidarum developed acute liver injury (ALI) and then acute liver failure (ALF) in less than 48 h. Because the patient developed atypical features, especially mildly elevated aminotransferases contrasting with very high blood ammonia levels (281 μmol/L), concomitant with normal serum creatinine, an inborn error of metabolism was suspected. We performed emergency metabolic analyses, stopped all protein intake and started with intravenous (i.v.) high caloric intake, nitrogen scavenger drugs and haemodialysis. The neurological and hepatic status of the patient quickly improved together with normalisation of her ammonemia levels. High plasma glutamine and urinary orotic acid, alongside low plasma arginine, citrulline and ornithine were suggestive of an ornithine transcarbamylase deficiency, later confirmed by molecular analyses. Foetal sex was female, as determined by foetal DNA analysis in maternal blood, and foetal development was unremarkable throughout the pregnancy. Delivery was induced at 39 weeks with a close monitoring of ammonemia levels and i.v. perfusion of carbohydrates and lipids during labour and immediately post-partum to avoid hypercatabolism. Delivery was uneventful and the patient delivered a healthy female baby. Urea cycle disorders should be contemplated in non-jaundiced patients with ALI or ALF, severe hyperammonemia and normal serum creatinine regardless of serum aminotransferase levels. The prompt recognition of this rare condition and the rapid initiation of adequate metabolic therapy are mandatory to prevent irreversible neurological sequelae and to avoid liver transplantation. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

DHTKD1 Deficiency Causes Charcot-Marie-Tooth Disease in Mice.

PubMed

Xu, Wang-Yang; Zhu, Houbao; Shen, Yan; Wan, Ying-Han; Tu, Xiao-Die; Wu, Wen-Ting; Tang, Lingyun; Zhang, Hong-Xin; Lu, Shun-Yuan; Jin, Xiao-Long; Fei, Jian; Wang, Zhu-Gang

2018-07-01

DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 that we identified previously causes Charcot-Marie-Tooth disease (CMT) type 2Q, one of the most common inherited neurological disorders affecting the peripheral nerves in the musculature. However, the comprehensive molecular mechanism underlying CMT2Q remains elusive. Here, we show that Dhtkd1 -/- mice mimic the major aspects of CMT2 phenotypes, characterized by progressive weakness and atrophy in the distal parts of limbs with motor and sensory dysfunctions, which are accompanied with decreased nerve conduction velocity. Moreover, DHTKD1 deficiency causes severe metabolic abnormalities and dramatically increased levels of 2-ketoadipic acid (2-KAA) and 2-aminoadipic acid (2-AAA) in urine. Further studies revealed that both 2-KAA and 2-AAA could stimulate insulin biosynthesis and secretion. Subsequently, elevated insulin regulates myelin protein zero ( Mpz ) transcription in Schwann cells via upregulating the expression of early growth response 2 (Egr2), leading to myelin structure damage and axonal degeneration. Finally, 2-AAA-fed mice do reproduce phenotypes similar to CMT2Q phenotypes. In conclusion, we have demonstrated that loss of DHTKD1 causes CMT2Q-like phenotypes through dysregulation of Mpz mRNA and protein zero (P 0 ) which are closely associated with elevated DHTKD1 substrate and insulin levels. These findings further indicate an important role of metabolic disorders in addition to mitochondrial insufficiency in the pathogenesis of peripheral neuropathies. Copyright © 2018 American Society for Microbiology.

Consistent abnormalities in metabolic network activity in idiopathic rapid eye movement sleep behaviour disorder.

PubMed

Wu, Ping; Yu, Huan; Peng, Shichun; Dauvilliers, Yves; Wang, Jian; Ge, Jingjie; Zhang, Huiwei; Eidelberg, David; Ma, Yilong; Zuo, Chuantao

2014-12-01

Rapid eye movement sleep behaviour disorder has been evaluated using Parkinson's disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. 18F-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0±5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5±7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6±5.0 years) and 16 moderate parkinsonian patients (age 56.9±12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network characterized by increased activity in pons, thalamus, medial frontal and sensorimotor areas, hippocampus, supramarginal and inferior temporal gyri, and posterior cerebellum, with decreased activity in occipital and superior temporal regions. Compared to the healthy control subjects, network expressions were elevated (P<0.0001) in the patients with this disorder and in the parkinsonian cohorts but decreased with disease progression. Parkinson's disease-related network activity was also elevated (P<0.0001) in the patients with rapid eye movement sleep behaviour disorder but lower than in the hemi-parkinsonian cohort. Abnormal metabolic networks may provide markers of idiopathic rapid eye movement sleep behaviour disorder to identify those at higher risk to develop neurodegenerative parkinsonism. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Metabolic and nutritional aspects of cancer.

PubMed

Krawczyk, Joanna; Kraj, Leszek; Ziarkiewicz, Mateusz; Wiktor-Jędrzejczak, Wiesław

2014-08-22

Cancer, being in fact a generalized disease involving the whole organism, is most frequently associated with metabolic deregulation, a latent inflammatory state and anorexia of various degrees. The pathogenesis of this disorder is complex, with multiple dilemmas remaining unsolved. The clinical consequences of the above-mentioned disturbances include cancer-related cachexia and anorexia-cachexia syndrome. These complex clinical entities worsen the prognosis, and lead to deterioration of the quality of life and performance status, and thus require multimodal treatment. Optimal therapy should include nutritional support coupled with pharmacotherapy targeted at underlying pathomechanisms of cachexia. Nevertheless, many issues still need explanation, and efficacious and comprehensive therapy of cancer-related cachexia remains a future objective.

Fatty Acids Consumption: The Role Metabolic Aspects Involved in Obesity and Its Associated Disorders

PubMed Central

Carla Inada, Aline; Marcelino, Gabriela; Maiara Lopes Cardozo, Carla; de Cássia Freitas, Karine; de Cássia Avellaneda Guimarães, Rita; Pereira de Castro, Alinne; Aragão do Nascimento, Valter; Aiko Hiane, Priscila

2017-01-01

Obesity and its associated disorders, such as insulin resistance, dyslipidemia, metabolic inflammation, dysbiosis, and non-alcoholic hepatic steatosis, are involved in several molecular and inflammatory mechanisms that alter the metabolism. Food habit changes, such as the quality of fatty acids in the diet, are proposed to treat and prevent these disorders. Some studies demonstrated that saturated fatty acids (SFA) are considered detrimental for treating these disorders. A high fat diet rich in palmitic acid, a SFA, is associated with lower insulin sensitivity and it may also increase atherosclerosis parameters. On the other hand, a high intake of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids may promote positive effects, especially on triglyceride levels and increased high-density lipoprotein (HDL) levels. Moreover, polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) are effective at limiting the hepatic steatosis process through a series of biochemical events, such as reducing the markers of non-alcoholic hepatic steatosis, increasing the gene expression of lipid metabolism, decreasing lipogenic activity, and releasing adiponectin. This current review shows that the consumption of unsaturated fatty acids, MUFA, and PUFA, and especially EPA and DHA, which can be applied as food supplements, may promote effects on glucose and lipid metabolism, as well as on metabolic inflammation, gut microbiota, and hepatic metabolism. PMID:29065507

Maternal educational level and the risk of persistent post-partum glucose metabolism disorders in women with gestational diabetes mellitus.

PubMed

Gante, Inês; Ferreira, Ana Carina; Pestana, Gonçalo; Pires, Daniela; Amaral, Njila; Dores, Jorge; do Céu Almeida, Maria; Sandoval, José Luis

2018-03-01

Gestational diabetes mellitus (GDM) occurs in 5-15% of pregnancies, and lower maternal educational attainment has been associated with higher risk of GDM. We aimed to determine if maternal education level is associated with persistent post-partum glucose metabolism disorders in women with GDM. Retrospective cohort study of women with GDM followed in 25 Portuguese health institutions between 2008 and 2012. Educational attainment was categorised into four levels. Prevalence of post-partum glucose metabolism disorders (type 2 diabetes mellitus, increased fasting plasma glucose or impaired glucose tolerance) was compared and adjusted odds ratios calculated controlling for confounders using logistic regression. We included 4490 women diagnosed with GDM. Educational level ranged as follows: 6.8% (n = 307) were at level 1 (≤ 6th grade), 34.6% (n = 1554) at level 2 (6-9th grade), 30.4% (n = 1364) at level 3 (10-12th grade) and 28.2% (n = 1265) at level 4 (≥ university degree). At 6 weeks post-partum re-evaluation, 10.9% (n = 491) had persistent glucose metabolism disorders. Educational levels 1 and 2 had a higher probability of persistent post-partum glucose metabolism disorders when compared to level 4 (OR = 2.37 [1.69;3.32], p < 0.001 and OR = 1.39 [1.09;1.76], p = 0.008, for level 1 and 2, respectively), an association that persisted in multivariable logistic regression adjusting for confounders (level 1 OR = 2.25 [1.53;3.33], p < 0.001; level 2 OR = 1.43 [1.09;1.89], p = 0.01). Persistent post-partum glucose metabolism disorders are frequent in women with GDM and associated with lower maternal educational level. Interventions aimed at this risk group may contribute towards a decrease in prevalence of post-partum glucose metabolism disorders.

Evaluation of plasma cholestane-3β,5α,6β-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism[S

PubMed Central

Boenzi, Sara; Deodato, Federica; Taurisano, Roberta; Goffredo, Bianca Maria; Rizzo, Cristiano; Dionisi-Vici, Carlo

2016-01-01

Oxysterols are intermediates of cholesterol metabolism and are generated from cholesterol via either enzymatic or nonenzymatic pathways under oxidative stress conditions. Cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC) have been proposed as new biomarkers for the diagnosis of Niemann-Pick type C (NP-C) disease, representing an alternative tool to the invasive and time-consuming method of fibroblast filipin test. To test the efficacy of plasma oxysterol determination for the diagnosis of NP-C, we systematically screened oxysterol levels in patients affected by different inherited disorders related with cholesterol metabolism, which included Niemann-Pick type B (NP-B) disease, lysosomal acid lipase (LAL) deficiency, Smith-Lemli-Opitz syndrome (SLOS), congenital familial hypercholesterolemia (FH), and sitosterolemia (SITO). As expected, NP-C patients showed significant increase of both C-triol and 7-KC. Strong increase of both oxysterols was observed in NP-B and less pronounced in LAL deficiency. In SLOS, only 7-KC was markedly increased, whereas in both FH and in SITO, oxysterol concentrations were normal. Interestingly, in NP-C alone, we observed that plasma oxysterols correlate negatively with patient’s age and positively with serum total bilirubin, suggesting the potential relationship between oxysterol levels and hepatic disease status. Our results indicate that oxysterols are reliable and sensitive biomarkers of NP-C. PMID:26733147

Offspring neuroimmune consequences of maternal malnutrition: Potential mechanism for behavioral impairments that underlie metabolic and neurodevelopmental disorders.

PubMed

Smith, B L; Reyes, T M

2017-10-01

Maternal malnutrition significantly increases offspring risk for both metabolic and neurodevelopmental disorders. Animal models of maternal malnutrition have identified behavioral changes in the adult offspring related to executive function and reward processing. Together, these changes in executive and reward-based behaviors likely contribute to the etiology of both metabolic and neurodevelopmental disorders associated with maternal malnutrition. Concomitant with the behavioral effects, maternal malnutrition alters offspring expression of reward-related molecules and inflammatory signals in brain pathways that control executive function and reward. Neuroimmune pathways and microglial interactions in these specific brain circuits, either in early development or later in adulthood, could directly contribute to the maternal malnutrition-induced behavioral phenotypes. Understanding these mechanisms will help advance treatment strategies for metabolic and neurodevelopmental disorders, especially noninvasive dietary supplementation interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Tinnitus sensation pre and post nutritional intervention in metabolic disorders.

PubMed

Almeida, Thamine Andrade Siqueira; Samelli, Alessandra Giannella; Mecca, Fabíola Del Nero; De Martino, Eliana; Paulino, Adriana Machado

2009-01-01

Different etiologies are related to tinnitus including metabolic disorders (blood glucose and lipids). The aim of this study was compare tinnitus severity by self-report measures pre and post nutritional intervention, using the Tinnitus Handicap Inventory. Participants of this study were twenty one male and female subjects, with ages ranging from 40 to 82 years. Inclusion criteria involved the presence of tinnitus and metabolic disorder diagnosed by laboratory exams. All subjects were submitted to a nutritional intervention program. Audiological evaluation and the Tinnitus Handicap Inventory were applied pre and post intervention. When comparing the presence of tinnitus pre and post intervention, data analysis indicates statistical difference concerning tinnitus sensation--71.5% of the individuals referred less impact of tinnitus in daily activities. An important difference was observed concerning tinnitus influence in subject's life by self-report measures. A direct relation between tinnitus and metabolic disorders in cases related with this symptom was verified.

[Metabolic disorders as paraneoplastic syndromes].

PubMed

Krug, S; Michl, P

2018-02-01

Paraneoplastic syndromes are characterized by the tumor-induced release of peptide hormones and/or the initiation of immune phenomena, which elicit clinical changes and alterations in laboratory parameters independent of the tumor size and spread. In addition to neurological, endocrinal and rheumatological phenotypes, metabolic alterations play a special role in the clinical routine as they commonly present with acute symptoms in an emergency situation and necessitate immediate diagnosis and prompt initiation of treatment. Metabolic alterations within the framework of malignant diseases should be treated in a multidisciplinary team and it is often necessary to perform monitoring and treatment in an intensive care unit. This article focuses on the diagnostic and therapeutic options for metabolic disorders due to paraneoplastic syndromes, such as hypercalcemia, hypocalcemia, hyperglycemia, hypoglycemia and a special variant of tumor-induced metabolic disorders due to tumor lysis syndrome.

[Oxygen-dependent energy deficit as related to the problems of ontogenetic development disorders and human sociobiological adaptation (theoretical and applied aspects)].

PubMed

Ilyukhina, V A; Kataeva, G V; Korotkov, A D; Chernysheva, E M

2015-01-01

The review states and argues theoretical propositions on the pathogenetic role of pre- and perinatal hypoxic-ischemic brain damage in the formation of sustained oxygen-dependent energy deficit underlying in further ontogenesis the following neurobiological abnormalities: a) a decline in the level of health and compensatory-adaptive capacities of the organism, b) disorders of the psycho-speech development and adaptive behavior in children, c) early development of neuropsychic diseases, g) addition of other types of brain energy metabolism (including glucose metabolism) disorders in chronic polyetiologic diseases young and middle-aged individuals. We highlight and theoretically substantiate the integrated physiological parameters of the oxygen-dependent energy deficit types. We address the features of abnormalities in neuroreflectory and neurohumora regulatory mechanisms of the wakefulness level and its vegetative and hemodynamic provision in different types of energy deficit in children with DSMD, ADHD and school maladjustment. The use of the state-of-the-art neuroimaging techniques significantly increased the possibility of the disintegration of regulatory processes and cognitive functions in children with psycho-speech delays and in a wide range of chronic polyetiologic diseases.

Altered heavy metals and transketolase found in autistic spectrum disorder.

PubMed

Obrenovich, Mark E; Shamberger, Raymond J; Lonsdale, Derrick

2011-12-01

Autism and autism spectrum disorder (ASD) are developmental brain disorders with complex, obscure, and multifactorial etiology. Our recent clinical survey of patient records from ASD children under the age of 6 years and their age-matched controls revealed evidence of abnormal markers of thiol metabolism, as well as a significant alteration in deposition of several heavy metal species, particularly arsenic, mercury, copper, and iron in hair samples between the groups. Altered thiol metabolism from heavy metal toxicity may be responsible for the biochemical alterations in transketolase, and are mechanisms for oxidative stress production, dysautonomia, and abnormal thiamine homeostasis. It is unknown why the particular metals accumulate, but we suspect that children with ASD may have particular trouble excreting thiol-toxic heavy metal species, many of which exist as divalent cations. Accumulation or altered mercury clearance, as well as concomitant oxidative stress, arising from redox-active metal and arsenic toxicity, offers an intriguing component or possible mechanism for oxidative stress-mediated neurodegeneration in ASD patients. Taken together, these factors may be more important to the etiology of this symptomatically diverse disease spectrum and may offer insights into new treatment approaches and avenues of exploration for this devastating and growing disease.

Overview of the Genetics of Alcohol Use Disorder

PubMed Central

Tawa, Elisabeth A.; Hall, Samuel D.; Lohoff, Falk W.

2016-01-01

Aims Alcohol Use Disorder (AUD) is a chronic psychiatric illness characterized by harmful drinking patterns leading to negative emotional, physical, and social ramifications. While the underlying pathophysiology of AUD is poorly understood, there is substantial evidence for a genetic component; however, identification of universal genetic risk variants for AUD has been difficult. Recent efforts in the search for AUD susceptibility genes will be reviewed in this article. Methods In this review, we provide an overview of genetic studies on AUD, including twin studies, linkage studies, candidate gene studies, and genome-wide association studies (GWAS). Results Several potential genetic susceptibility factors for AUD have been identified, but the genes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), have been found to be protective against the development of AUD. GWAS have also identified a heterogeneous list of SNPs associated with AUD and alcohol-related phenotypes, emphasizing the complexity and heterogeneity of the disorder. In addition, many of these findings have small effect sizes when compared to alcohol metabolism genes, and biological relevance is often unknown. Conclusions Although studies spanning multiple approaches have suggested a genetic basis for AUD, identification of the genetic risk variants has been challenging. Some promising results are emerging from GWAS studies; however, larger sample sizes are needed to improve GWAS results and resolution. As the field of genetics is rapidly developing, whole genome sequencing could soon become the new standard of interrogation of the genes and neurobiological pathways which contribute to the complex phenotype of AUD. Short summary This review examines the genetic underpinnings of Alcohol Use Disorder (AUD), with an emphasis on GWAS approaches for identifying genetic risk variants. The most promising results associated with AUD and alcohol-related phenotypes have included SNPs of the alcohol metabolism genes ADH and ALDH. PMID:27445363

The central nervous system in animal models of hyperhomocysteinemia.

PubMed

Troen, Aron M

2005-09-01

Growing epidemiological evidence of associations between mildly elevated plasma homocysteine with age-related cognitive impairment, neurodegenerative and cerebrovascular disease has stimulated interest in the role of homocysteine in neurological and neuropsychiatric disorders. Homocysteine is an intermediate in the folate, vitamin B12 and B6 dependent pathways of one-carbon and sulfur amino acid metabolism. Impairments of these pathways may cause CNS dysfunction by promoting the intracellular generation of homocysteine, which is postulated to have vasotoxic and neurotoxic properties. It might also inhibit the methylation of myelin basic protein and membrane phospholipids, or disrupt biogenic amine metabolism and many other vital CNS reactions. However, it is unclear which, if any, of these putative mechanisms underlies the epidemiological associations. Genetic mouse models of hyperhomocysteinemia suggest that the primary metabolic disturbances rather than homocysteine per se may be important in determining neurological outcomes. However, severe and early developmental abnormalities in these mice limit their usefulness for understanding the relation of hyperhomocysteinemia to adult CNS disorders. Pharmacologic and dietary studies on homocysteine in rodents have reported heightened neuronal sensitivity to neurotoxic insults, neurochemical abnormalities and cerebrovascular dysfunction. Such studies are consistent with a causal relationship, but they fail to distinguish between effects that might result from a dietary imbalance and those that might be caused by homocysteine per se. Future work should be directed towards refining these models in order to distinguish between the effects of homocysteine and its determinants on neurological and behavioral outcomes that represent different CNS disorders.

Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

PubMed

Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

2013-01-01

Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

DTIC Science & Technology

2014-07-01

Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders PRINCIPAL INVESTIGATOR: Alexandre Bonnin, PhD CONTRACTING...Fetal Programming of Neurodevelopmental Disorders 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Alexandre Bonnin, PhD; Betty...metabolism by maternal inflammation during early gestation constitutes a new molecular pathway for the fetal programming of neurodevelopmental

Role of folate in nonalcoholic fatty liver disease.

PubMed

Sid, Victoria; Siow, Yaw L; O, Karmin

2017-10-01

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

Stepwise approach to myopathy in systemic disease.

PubMed

Chawla, Jasvinder

2011-01-01

Muscle diseases can constitute a large variety of both acquired and hereditary disorders. Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness myopathy, metabolic, and myopathies with other systemic disorders. Patients with systemic myopathies often present acutely or sub acutely. On the other hand, familial myopathies or dystrophies generally present in a chronic fashion with exceptions of metabolic myopathies where symptoms on occasion can be precipitated acutely. Most of the inflammatory myopathies can have a chance association with malignant lesions; the incidence appears to be specifically increased only in patients with dermatomyositis. In dealing with myopathies associated with systemic illnesses, the focus will be on the acquired causes. Management is beyond the scope of this chapter. Prognosis is based upon the underlying cause and, most of the time, carries a good prognosis. In order to approach a patient with suspected myopathy from systemic disease, a stepwise approach is utilized.

Biochemical Basis of CO2-Related Internal Browning Disorders in Pears (Pyrus communis L. cv. Rocha) during Long-Term Storage.

PubMed

Deuchande, Teresa; Larrigaudière, Christian; Giné-Bordonaba, Jordi; Carvalho, Susana M P; Vasconcelos, Marta W

2016-06-01

This study aimed at understanding the biochemical basis of internal browning disorders (IBDs) in 'Rocha' pear. For this purpose, the effects of storage under normal controlled atmosphere (CA) (3 kPa of O2 + 0.5 kPa of CO2) and IBD-inducing CA (1 kPa of O2 + 10 kPa of CO2) on the antioxidant and fermentative metabolisms and polyphenol oxidase (PPO) activity and phenolics concentration were studied. The higher IBD incidence in high CO2-stored fruits was positively correlated with fermentative metabolites and negatively with ascorbate and H2O2 concentrations, and it was linked to PPO activation. These results indicate that both the antioxidant and fermentative metabolisms are involved in the occurrence of IBD in 'Rocha' pear. From the integration of the biochemical and enzymatic data, a schematic model illustrating the effects of high CO2 and low O2 in 'Rocha' pears during long-term storage was constructed.

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models.

PubMed

Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H G

2011-03-01

The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders.

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

PubMed Central

Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H. G.

2011-01-01

The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders. PMID:21062955

NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.

PubMed

Xiao, Wusheng; Wang, Rui-Sheng; Handy, Diane E; Loscalzo, Joseph

2018-01-20

The nicotinamide adenine dinucleotide (NAD + )/reduced NAD + (NADH) and NADP + /reduced NADP + (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD + -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD + precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.

Green tea polyphenol treatment attenuates atherosclerosis in high-fat diet-fed apolipoprotein E-knockout mice via alleviating dyslipidemia and up-regulating autophagy

PubMed Central

Jiang, Jinjin; Yu, Pengxin; Zhang, Guofu; Zhang, Guanghui; Liu, Xiaoting

2017-01-01

Background: Green tea polyphenol (GTP) is a polyphenol source from green tea that has drawn wide attention owing to epidemiological evidence of its beneficial effects in the prevention of cardiovascular disease; the underlying molecular mechanisms of these effects are not well understood. This study aimed to investigate the effects of GTP treatment on autophagy regulation in the vessel wall and lipid metabolism of HFD-fed male ApoE-knockout mice. Methods: Adult male ApoE-knockout mice (n = 30) fed with a high-fat diet (HFD) were treated with either vehicle or GTP (3.2 or 6.4 g/L) administered via drinking water for 15 weeks, and C57BL/6J mice fed with standard chow diet (STD) were used as the control group. Metabolic parameters, expression of key mRNAs and proteins of hepatic lipid metabolism and autophagy in the vessel wall of mice were determined after the 15-week treatment. Results: A HFD induced atherosclerosis formation and lipid metabolism disorders as well as reduced autophagy expression in the vessel wall of ApoE-knockout mice, but GTP treatment alleviated the lipid metabolism disorders, decreased the oxLDL levels in serum, and increased the mRNA and protein expressions of hepatic PPARα and autophagy markers (LC3, Beclin1 and p62) in the vessel wall of ApoE-knockout mice. Conclusions: Our findings suggest that GTP supplementation showed marked suppression of atherogenesis through improved lipid metabolism as well as through a direct impact on oxLDL and autophagy flux in the vessel wall. PMID:28777810

Living with an inborn error of metabolism detected by newborn screening-parents' perspectives on child development and impact on family life.

PubMed

Gramer, Gwendolyn; Haege, Gisela; Glahn, Esther M; Hoffmann, Georg F; Lindner, Martin; Burgard, Peter

2014-03-01

Newborn screening for inborn errors of metabolism is regarded as highly successful by health professionals. Little is known about parents' perspectives on child development and social impact on families. Parents of 187 patients with metabolic disorders detected by newborn screening rated child development, perceived burdens on child and family, and future expectations on a questionnaire with standardized answers. Parental ratings were compared with standardized psychometric test results. Regression analysis was performed to identify factors associated with extent of perceived burden. In 26.2% of patients, parents perceived delays in global development and/or specific developmental domains (physical, social, intellectual, language). Parents expected normal future development in 95.7%, and an independent adult life for their child in 94.6%. Comparison with psychometric test results showed that parents of children with cognitive impairments tended to overrate their child's abilities. Mild/medium burden posed on the family (child) by the metabolic disorder was stated by 56.1% (48.9%) of parents, severe/very severe burden by 19.3% (8.6%). One third of families reported financial burden due to the metabolic disorder. Dietary treatment and diagnoses with risk for metabolic decompensation despite treatment were associated with higher perceived burden for the family. Disorders rated as potentially very burdensome by experts were not rated accordingly by parents, demonstrating different perspectives of professionals and parents. Although newborn screening leads to favourable physical and cognitive outcome, living with a metabolic disorder may cause considerable stress on patients and families, emphasizing the need for comprehensive multidisciplinary care including psychological and social support.

Metabolic effect of obesity on polycystic ovary syndrome in adolescents: a meta-analysis.

PubMed

Li, Li; Feng, Qiong; Ye, Ming; He, Yaojuan; Yao, Aling; Shi, Kun

2017-11-01

This meta-analysis provides an updated and comprehensive estimate of the effects of obesity on metabolic disorders in adolescent polycystic ovary syndrome (PCOS). Relevant articles consistent with the search terms published up to 31 January 2014 were retrieved from PubMed, EMBASE, PsycINFO and CENTRAL. Thirteen articles (16 independent studies) conformed to the inclusion criteria. The evaluated outcomes were the metabolic parameters of obese adolescents with PCOS (case group) relative to normal-weight adolescents with PCOS, or obese adolescents without PCOS. Compared with normal-weight adolescents with PCOS, the case group had significantly lower sex hormone-binding globulin and high-density lipoprotein cholesterol, and significantly higher triglycerides, leptin, fasting insulin, low-density lipoprotein cholesterol and free testosterone levels. Relative to obese adolescents without PCOS, the case group had significantly higher fasting insulin, low-density lipoprotein cholesterol, free testosterone levels and 2-h glucose during the oral glucose tolerance test. These results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Impact statement What is already known about this subject: Obesity and PCOS share many of the same metabolic disorders, for example, hyperandrogenism and hyperinsulinemia with subsequent insulin resistance. Knowledge regarding metabolic features in obese adolescents with PCOS is limited, and there is concern whether obesity and PCOS are related. What do the results of this study add: Relative to PCOS adolescents of normal weight, obese adolescents with PCOS (the case group) had significantly lower SHBG and HDL-C, and significantly higher triglycerides, leptin, fasting insulin, LDL-C and free testosterone levels. The results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. What are the implications of these findings for clinical practice and/or further research: Obesity, metabolic disorders and PCOS in adolescents are associated. Obesity exacerbates metabolic disorders in adolescent PCOS. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Therapeutic intervention combined with lifestyle modification may provide better treatment for adolescent PCOS. The aetiologies of PCOS combined with obesity in adolescents require further investigation.

Bone scan in metabolic bone diseases. Review.

PubMed

Abdelrazek, Saeid; Szumowski, Piotr; Rogowski, Franciszek; Kociura-Sawicka, Agnieszka; Mojsak, Małgorzata; Szorc, Małgorzata

2012-08-25

Metabolic bone disease encompasses a number of disorders that tend to present a generalized involvement of the whole skeleton. The disorders are mostly related to increased bone turnover and increased uptake of radiolabelled diphosphonate. Skeletal uptake of 99mTc-labelled diphosphonate depends primarily upon osteoblastic activity, and to a lesser extent, skeletal vascularity. A bone scan image therefore presents a functional display of total skeletal metabolism and has valuable role to play in the assessment of patients with metabolic bone disorders. However, the bone scan appearances in metabolic bone disease are often non-specific, and their recognition depends on increased tracer uptake throughout the whole skeleton. It is the presence of local lesions, as in metastatic disease, that makes a bone scan appearance obviously abnormal. In the early stages, there will be difficulty in evaluating the bone scans from many patients with metabolic bone disease. However, in the more severe cases scan appearances can be quite striking and virtually diagnostic.

Strategies for Reversing the Effects of Metabolic Disorders Induced as a Consequence of Developmental Programming

PubMed Central

Vickers, M. H.; Sloboda, D. M.

2012-01-01

Obesity and the metabolic syndrome have reached epidemic proportions worldwide with far-reaching health care and economic implications. The rapid increase in the prevalence of these disorders suggests that environmental and behavioral influences, rather than genetic causes, are fueling the epidemic. The developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal, and early infant phases of life and the subsequent development of metabolic disorders in later life. In particular, the impact of poor maternal nutrition on susceptibility to later life metabolic disease in offspring is now well documented. Several studies have now shown, at least in experimental animal models, that some components of the metabolic syndrome, induced as a consequence of developmental programming, are potentially reversible by nutritional or targeted therapeutic interventions during windows of developmental plasticity. This review will focus on critical windows of development and possible therapeutic avenues that may reduce metabolic and obesogenic risk following an adverse early life environment. PMID:22783205

The use of ketogenic diet in special situations: expanding use in intractable epilepsy and other neurologic disorders

PubMed Central

2012-01-01

The ketogenic diet has been widely used and proved to be effective for intractable epilepsy. Although the mechanisms underlying its anti-epileptic effects remain to be proven, there are increasing experimental evidences for its neuroprotective effects along with many researches about expanding use of the diet in other neurologic disorders. The first success was reported in glucose transporter type 1 deficiency syndrome, in which the diet served as an alternative metabolic source. Many neurologic disorders share some of the common pathologic mechanisms such as mitochondrial dysfunction, altered neurotransmitter function and synaptic transmission, or abnormal regulation of reactive oxygen species, and the role of the ketogenic diet has been postulated in these mechanisms. In this article, we introduce an overview about the expanding use and emerging trials of the ketogenic diet in various neurologic disorders excluding intractable epilepsy and provide explanations of the mechanisms in that usage. PMID:23049588

[Neurotic disorders: clinical and biochemical comparison].

PubMed

Riazantseva, N V; Novitskiĭ, V V

2003-05-01

Parameters of lipid peroxidation (LP) and those of the lipid composition of membrane erythrocytes were examined in 22 patients with neurotic disorders (adaptation disorders and neurasthenia). 45 healthy donors were in the control group. The deposition of cholesterol and of lysophosphotidylcholine as well as a reduced mean level of phosphatidylethanolamine were observed in the erythrocyte membrane of patients with neuroses. An increased mean content of malonic dialdehyde and of diene conjugates in the erythrocyte membrane and reduced mean values of the activity of antioxidant catalase enzyme were detected. However, the cluster analysis made it possible to establish an intensification of LP processes only in patients with the disease duration below three months. It is not ruled out that the reason of the detected heterogeneity of changed parameters characterizing the structural-and-metabolic status of erythrocytes in patients with neurotic disorders is related with differing natures of the adaptation abilities of the body under the influence of various stress factors.

[THE FACTORS OF THE PROGRESSION OF METABOLIC DISORDERS IN THE PANCREAS IN PATIENTS WITH ASSOCIATED CLINICAL VARIANTS OF THE CHRONIC PANCREATITIS AND TYPE 2 DIABETES MELLITUS].

PubMed

Zhuravlyova, L V; Shekhovtsova, Y O

2015-01-01

The purpose of the present study was to determine the causal factors of the progression of metabolic disorders in pancreatic tissue and their relationships in patients with assotiated clinical variants of chronic pancreatitis (CP) and type 2 diabetes mellitus (T2DM). The study involved of 76 patients with CP and T2DM. The causes of progression of metabolic disorders in the pancreas in patients with associated clinical variants of CP and T2DM has been analyzed. The most significant of them were insulin resistance and abdominal obesity, which promotes early formation of the metabolic syndrome and the activation of fibrogenesis and steatosis in the pancreas and is caused by dyslipidemia, impaired glucose metabolism and the development of systemic inflammation and imbalance of adipocytokines. The relationships between adipocytokines, body weight and individual components of the metabolic syndrome in patients with CP and T2DM suggests the involvement of these hormones of adipose tissue in the formation of the metabolic syndrome and its components.

Stress, autonomic imbalance, and the prediction of metabolic risk: A model and a proposal for research.

PubMed

Wulsin, Lawson; Herman, James; Thayer, Julian F

2018-03-01

Devising novel prevention strategies for metabolic disorders will depend in part on the careful elucidation of the common pathways for developing metabolic risks. The neurovisceral integration model has proposed that autonomic imbalance plays an important role in the pathway from acute and chronic stress to cardiovascular disease. Though generally overlooked by clinicians, autonomic imbalance (sympathetic overactivity and/or parasympathetic underactivity) can be measured and modified by methods that are available in primary care. This review applies the neurovisceral integration concept to the clinical setting by proposing that autonomic imbalance plays a primary role in the development of metabolic risks. We present a testable model, a systematic review of the evidence in support of autonomic imbalance as a predictor for metabolic risks, and specific approaches to test this model as a guide to future research on the role of stress in metabolic disorders. We propose that autonomic imbalance deserves consideration by researchers, clinicians, and policymakers as a target for early interventions to prevent metabolic disorders. Published by Elsevier Ltd.

Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy.

PubMed

Vanni, Nicola; Fruscione, Floriana; Ferlazzo, Edoardo; Striano, Pasquale; Robbiano, Angela; Traverso, Monica; Sander, Thomas; Falace, Antonio; Gazzerro, Elisabetta; Bramanti, Placido; Bielawski, Jacek; Fassio, Anna; Minetti, Carlo; Genton, Pierre; Zara, Federico

2014-08-01

Alterations of sphingolipid metabolism are implicated in the pathogenesis of many neurodegenerative disorders. We identified a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, in 4 siblings affected by a progressive disorder with myoclonic epilepsy and dementia. CerS1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. We demonstrated that the mutation decreases C18-ceramide levels. In addition, we showed that downregulation of CerS1 in a neuroblastoma cell line triggers ER stress response and induces proapoptotic pathways. This study demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans. © 2014 American Neurological Association.

Genetic overlap between type 2 diabetes and major depressive disorder identified by bioinformatics analysis.

PubMed

Ji, Hong-Fang; Zhuang, Qi-Shuai; Shen, Liang

2016-04-05

Our study investigated the shared genetic etiology underlying type 2 diabetes (T2D) and major depressive disorder (MDD) by analyzing large-scale genome wide association studies statistics. A total of 496 shared SNPs associated with both T2D and MDD were identified at p-value ≤ 1.0E-07. Functional enrichment analysis showed that the enriched pathways pertained to immune responses (Fc gamma R-mediated phagocytosis, T cell and B cell receptors signaling), cell signaling (MAPK, Wnt signaling), lipid metabolism, and cancer associated pathways. The findings will have potential implications for future interventional studies of the two diseases.

Genetics Home Reference: isolated sulfite oxidase deficiency

MedlinePlus

... Metabolic Disorders (CLIMB) March of Dimes: Amino Acid Metabolism Disorders The Compassionate Friends GeneReviews (1 link) Isolated Sulfite Oxidase Deficiency ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...

Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder.

PubMed

Saito, Tomoyuki; Tamura, Maasa; Chiba, Yuhei; Katsuse, Omi; Suda, Akira; Kamada, Ayuko; Ikura, Takahiro; Abe, Kie; Ogawa, Matsuyoshi; Minegishi, Kaoru; Yoshimi, Ryusuke; Kirino, Yohei; Ihata, Atsushi; Hirayasu, Yoshio

2017-08-15

Depression is frequently observed in patients with systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) patients often exhibit cerebral hypometabolism, but the association between cerebral metabolism and depression remains unclear. To elucidate the features of cerebral metabolism in SLE patients with depression, we performed brain 18F-fluoro-d-glucose positron emission tomography (FDG-PET) on SLE patients with and without major depressive disorder. We performed brain FDG-PET on 20 SLE subjects (5 male, 15 female). The subjects were divided into two groups: subjects with major depressive disorder (DSLE) and subjects without major depressive disorder (non-DSLE). Cerebral glucose metabolism was analyzed using the three-dimensional stereotactic surface projection (3D-SSP) program. Regional metabolism was evaluated by stereotactic extraction estimation (SEE), in which the whole brain was divided into segments. Every SLE subject exhibited cerebral hypometabolism, in contrast to the normal healthy subjects. Regional analysis revealed a significantly lower ER in the left medial frontal gyrus (p=0.0055) and the right medial frontal gyrus (p=0.0022) in the DSLE group than in the non-DSLE group. Hypometabolism in the medial frontal gyrus may be related to major depressive disorder in SLE. Larger studies are needed to clarify this relationship. Copyright © 2017 Elsevier B.V. All rights reserved.

Insurance coverage of medical foods for treatment of inherited metabolic disorders

PubMed Central

Berry, Susan A.; Kenney, Mary Kay; Harris, Katharine B.; Singh, Rani H.; Cameron, Cynthia A.; Kraszewski, Jennifer N.; Levy-Fisch, Jill; Shuger, Jill F.; Greene, Carol L.; Lloyd-Puryear, Michele A.; Boyle, Coleen A.

2015-01-01

Purpose Treatment of inherited metabolic disorders is accomplished by use of specialized diets employing medical foods and medically necessary supplements. Families seeking insurance coverage for these products express concern that coverage is often limited; the extent of this challenge is not well defined. Methods To learn about limitations in insurance coverage, parents of 305 children with inherited metabolic disorders completed a paper survey providing information about their use of medical foods, modified low-protein foods, prescribed dietary supplements, and medical feeding equipment and supplies for treatment of their child's disorder as well as details about payment sources for these products. Results Although nearly all children with inherited metabolic dis orders had medical coverage of some type, families paid “out of pocket” for all types of products. Uncovered spending was reported for 11% of families purchasing medical foods, 26% purchasing supplements, 33% of those needing medical feeding supplies, and 59% of families requiring modified low-protein foods. Forty-two percent of families using modified low-protein foods and 21% of families using medical foods reported additional treatment-related expenses of $100 or more per month for these products. Conclusion Costs of medical foods used to treat inherited metabolic disorders are not completely covered by insurance or other resources. PMID:23598714

Red-koji fermented red ginseng ameliorates high fat diet-induced metabolic disorders in mice.

PubMed

Kim, Chang Man; Yi, Seong Joon; Cho, Il Je; Ku, Sae Kwang

2013-10-30

Fermentation of medicinal herbs improves their pharmacological efficacy. In this study, we investigated the effects of red-koji fermented red ginseng (fRG) on high-fat diet (HFD)-mediated metabolic disorders, and those effects were compared to those of non-fermented red ginseng (RG). fRG (500, 250 or 125 mg/kg), RG (250 mg/kg), simvastatin (10 mg/kg), silymarin (100 mg/kg) and metformin (250 mg/kg) were orally administered from 1 week after initiation of HFD supply for 84 days. The diameter of adipocytes in periovarian and abdominal fat pads and the thickness of the abdominal fat were significantly decreased by fRG treatment, while HFD-mediated weight gain was partly alleviated by fRG in a dose-dependent manner. Moreover, biochemical and histomorphometrical analyses clearly indicated that fRG significantly inhibited HFD-induced metabolic disorders such as hyperglycemia, hyperlipidemia, hepatopathy and nephropathy in a dose-dependent manner. More favorable pharmacological effects on HFD-mediated metabolic disorders were also observed with fRG compared to an equal dose of RG. This finding provides direct evidence that the pharmacological activities of RG were enhanced by red-koji fermentation, and fRG could be a neutraceutical resource for the alleviation of obesity-mediated metabolic disorders.

Molecular Mechanisms in Amyotrophic Lateral Sclerosis: The Role of Angiogenin, a Secreted RNase

PubMed Central

Aparicio-Erriu, Isabela M.; Prehn, Jochen H. M.

2012-01-01

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease caused by the loss of motoneurons. The precise molecular and cellular basis for neuronal death is not yet well established, but the contemporary view is that it is a culmination of multiple aberrant biological processes. Among the proposed mechanisms of motoneuron degeneration, alterations in the homeostasis of RNA binding proteins (RBP) and the consequent changes in RNA metabolism have received attention recently. The ribonuclease, angiogenin was one of the first RBPs associated with familial and sporadic ALS. It is enriched in motoneurons under physiological conditions, and is required for motoneuron survival under stress conditions. Furthermore, delivery of angiogenin protects cultured motoneurons against stress-induced injury, and significantly increases the survival of motoneurons in SODG93A mice. In this overview on the role of angiogenin in RNA metabolism and in the control of motoneuron survival, we discuss potential pathogenic mechanisms of angiogenin dysfunction relevant to ALS and other neurodegenerative disorders. We also discuss recent evidence demonstrating that angiogenin secreted from stressed motoneurons may alter RNA metabolism in astrocytes. PMID:23181008

Molecular Mechanisms in Amyotrophic Lateral Sclerosis: The Role of Angiogenin, a Secreted RNase.

PubMed

Aparicio-Erriu, Isabela M; Prehn, Jochen H M

2012-01-01

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease caused by the loss of motoneurons. The precise molecular and cellular basis for neuronal death is not yet well established, but the contemporary view is that it is a culmination of multiple aberrant biological processes. Among the proposed mechanisms of motoneuron degeneration, alterations in the homeostasis of RNA binding proteins (RBP) and the consequent changes in RNA metabolism have received attention recently. The ribonuclease, angiogenin was one of the first RBPs associated with familial and sporadic ALS. It is enriched in motoneurons under physiological conditions, and is required for motoneuron survival under stress conditions. Furthermore, delivery of angiogenin protects cultured motoneurons against stress-induced injury, and significantly increases the survival of motoneurons in SOD(G93A) mice. In this overview on the role of angiogenin in RNA metabolism and in the control of motoneuron survival, we discuss potential pathogenic mechanisms of angiogenin dysfunction relevant to ALS and other neurodegenerative disorders. We also discuss recent evidence demonstrating that angiogenin secreted from stressed motoneurons may alter RNA metabolism in astrocytes.

Developmental programming of hypothalamic neuronal circuits: impact on energy balance control

PubMed Central

Gali Ramamoorthy, Thanuja; Begum, Ghazala; Harno, Erika; White, Anne

2015-01-01

The prevalence of obesity in adults and children has increased globally at an alarming rate. Mounting evidence from both epidemiological studies and animal models indicates that adult obesity and associated metabolic disorders can be programmed by intrauterine and early postnatal environment- a phenomenon known as “fetal programming of adult disease.” Data from nutritional intervention studies in animals including maternal under- and over-nutrition support the developmental origins of obesity and metabolic syndrome. The hypothalamic neuronal circuits located in the arcuate nucleus controlling appetite and energy expenditure are set early in life and are perturbed by maternal nutritional insults. In this review, we focus on the effects of maternal nutrition in programming permanent changes in these hypothalamic circuits, with experimental evidence from animal models of maternal under- and over-nutrition. We discuss the epigenetic modifications which regulate hypothalamic gene expression as potential molecular mechanisms linking maternal diet during pregnancy to the offspring's risk of obesity at a later age. Understanding these mechanisms in key metabolic genes may provide insights into the development of preventative intervention strategies. PMID:25954145

Incidence, nature, and etiology of metabolic acidosis in dogs and cats.

PubMed

Hopper, K; Epstein, S E

2012-01-01

Metabolic acidosis is an important abnormality in ill and injured dogs and cats. To describe the incidence, nature, and etiology of metabolic acidosis in dogs and cats that had arterial or venous blood gases measured for any reason at a university teaching hospital. Dogs and cats at the Veterinary Medical Teaching Hospital. Acid base parameters and electrolyte and lactate concentrations in dogs and cats measured during a 13-month period were retrospectively retrieved from a computer database. Metabolic acidosis was defined as a standardized base excess (SBE) in dogs of <-4 mmol/L and in cats <-5 mmol/L. A total of 1,805 dogs and cats were included; of these, 887 (49%) were classified as having a metabolic acidosis (753 dogs and 134 cats). Primary metabolic acidosis was the most common disorder in dogs, whereas mixed acid base disorder of metabolic acidosis and respiratory acidosis was most common in cats. Hyperchloremic metabolic acidosis was more common than a high anion gap (AG) metabolic acidosis; 25% of dogs and 34% of cats could not be classified as having either a hyperchloremic metabolic acidosis or a high AG metabolic acidosis. Metabolic acidosis was found commonly in this patient population and was associated with a wide variety of disease processes. Mixed acid base disorders occur frequently and routine categorization of metabolic acidosis based on the presence of high AG or hyperchloremia may be misleading in a large proportion of cases. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Length of psychiatric hospitalization is correlated with CYP2D6 functional status in inpatients with major depressive disorder

PubMed Central

Ruaño, Gualberto; Szarek, Bonnie L; Villagra, David; Gorowski, Krystyna; Kocherla, Mohan; Seip, Richard L; Goethe, John W; Schwartz, Harold I

2016-01-01

Aim This study aimed to determine the effect of the CYP2D6 genotype on the length of hospitalization stay for patients treated for major depressive disorder. Methods A total of 149 inpatients with a diagnosis of major depressive disorder at the Institute of Living, Hartford Hospital (CT, USA), were genotyped to detect altered alleles in the CYP2D6 gene. Prospectively defined drug metabolism indices (metabolic reserve, metabolic alteration and allele alteration) were determined quantitatively and assessed for their relationship to length of hospitalization stay. Results Hospital stay was significantly longer in deficient CYP2D6 metabolizers (metabolic reserve <2) compared with functional or suprafunctional metabolizers (metabolic reserve ≥2; 7.8 vs 5.7 days, respectively; p = 0.002). Conclusion CYP2D6 enzymatic functional status significantly affected length of hospital stay, perhaps due to reduced efficacy or increased side effects of the medications metabolized by the CYP2D6 isoenzyme. Functional scoring of CYP2D6 alleles may have a substantial impact on the quality of care, patient satisfaction and the economics of psychiatric treatment. PMID:23734807

Hearing Loss, Dizziness, and Carbohydrate Metabolism

PubMed Central

Albernaz, Pedro L. Mangabeira

2015-01-01

Introduction  Metabolic activity of the inner ear is very intense, and makes it sensitive to changes in the body homeostasis. This study involves a group of patients with inner ear disorders related to carbohydrate metabolism disturbances, including hearing loss, tinnitus, dizziness, and episodes of vertigo. Objectives  To describe the symptoms of metabolic inner ear disorders and the examinations required to establish diagnoses. These symptoms are often the first to allow for an early diagnosis of metabolic disorders and diabetes. Methods  Retrospective study of 376 patients with inner ear symptoms suggestive of disturbances of carbohydrate metabolism. The authors present patientś clinical symptoms and clinical evaluations, with emphasis on the glucose and insulin essays. Results  Authors based their conclusions on otolaryngological findings, diagnostic procedures and treatment principles. They found that auditory and vestibular symptoms usually occur prior to other manifestations of metabolic changes, leading to an early diagnosis of hyperinsulinemia, intestinal sugar malabsorption or diabetes. Previously undiagnosed diabetes mellitus type II was found in 39 patients. Conclusions  The identification of carbohydrate metabolism disturbances is important not only to minimize the patients' clinical symptoms, but also to help maintain their general health. PMID:27413410

Chronic exposure to low concentrations of lead induces metabolic disorder and dysbiosis of the gut microbiota in mice.

PubMed

Xia, Jizhou; Jin, Cuiyuan; Pan, Zihong; Sun, Liwei; Fu, Zhengwei; Jin, Yuanxiang

2018-08-01

Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that can contaminate food and water. In this study, effects of chronic exposure to low concentrations of Pb on metabolism and gut microbiota were evaluated in mice. It was observed that exposure of mice to 0.1mg/L Pb, supplied via drinking water, for 15weeks increased hepatic TG and TCH levels. The levels of some key genes related to lipid metabolism in the liver increased significantly in Pb-treated mice. For the gut microbiota, at the phylum level, the relative abundance of Firmicutes and Bacteroidetes changed obviously in the feces and the cecal contents of mice exposed to 0.1mg/L Pb for 15weeks. In addition, 16s rRNA gene sequencing further discovered that Pb exposure affected the structure and richness of the gut microbiota. Moreover, a 1 H NMR metabolic analysis unambiguously identified 31 metabolites, and 15 metabolites were noticeably altered in 0.1mg/L Pb-treated mice. Taken together, the data indicate that chronic Pb exposure induces dysbiosis of the gut microbiota and metabolic disorder in mice. Chronic Pb exposure induces metabolic disorder, dysbiosis of the gut microbiota and hepatic lipid metabolism disorder in mice. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder.

PubMed

Yoon, Sujung; Kim, Jieun E; Hwang, Jaeuk; Kim, Tae-Suk; Kang, Hee Jin; Namgung, Eun; Ban, Soonhyun; Oh, Subin; Yang, Jeongwon; Renshaw, Perry F; Lyoo, In Kyoon

2016-09-15

Creatine monohydrate (creatine) augmentation has the potential to accelerate the clinical responses to and enhance the overall efficacy of selective serotonin reuptake inhibitor treatment in women with major depressive disorder (MDD). Although it has been suggested that creatine augmentation may involve the restoration of brain energy metabolism, the mechanisms underlying its antidepressant efficacy are unknown. In a randomized, double-blind, placebo-controlled trial, 52 women with MDD were assigned to receive either creatine augmentation or placebo augmentation of escitalopram; 34 subjects participated in multimodal neuroimaging assessments at baseline and week 8. Age-matched healthy women (n = 39) were also assessed twice at the same intervals. Metabolic and network outcomes were measured for changes in prefrontal N-acetylaspartate and changes in rich club hub connections of the structural brain network using proton magnetic resonance spectroscopy and diffusion tensor imaging, respectively. We found MDD-related metabolic and network dysfunction at baseline. Improvement in depressive symptoms was greater in patients receiving creatine augmentation relative to placebo augmentation. After 8 weeks of treatment, prefrontal N-acetylaspartate levels increased significantly in the creatine augmentation group compared with the placebo augmentation group. Increment in rich club hub connections was also greater in the creatine augmentation group than in the placebo augmentation group. N-acetylaspartate levels and rich club connections increased after creatine augmentation of selective serotonin reuptake inhibitor treatment. Effects of creatine administration on brain energy metabolism and network organization may partly underlie its efficacy in treating women with MDD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Metabolic and vascular origins of the BOLD effect: Implications for imaging pathology and resting-state brain function.

PubMed

Mark, Clarisse I; Mazerolle, Erin L; Chen, J Jean

2015-08-01

The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes in blood oxygenation resulting from the relative balance between cerebral oxygen metabolism (through neural activity) and oxygen supply (through cerebral blood flow and volume). As such, there are cases in which BOLD signals might be dissociated from neural activity, leading to misleading results. The emphasis of this review is to develop a critical perspective for interpreting BOLD results, through a comprehensive consideration of BOLD's metabolic and vascular underpinnings. We demonstrate that such an understanding is especially important under disease or resting conditions. We also describe state-of-the-art acquisition and analytical techniques to reveal physiological information on the mechanisms underlying measured BOLD signals. With these goals in mind, this review is structured to provide a fundamental understanding of: 1) the physiological and physical sources of the BOLD contrast; 2) the extraction of information regarding oxidative metabolism and cerebrovascular reactivity from the BOLD signal, critical to investigating neuropathology; and 3) the fundamental importance of metabolic and vascular mechanisms for interpreting resting-state BOLD measurements. © 2015 Wiley Periodicals, Inc.

Regional cerebral glucose metabolic abnormality in Prader-Willi syndrome: A 18F-FDG PET study under sedation.

PubMed

Kim, Sang Eun; Jin, Dong-Kyu; Cho, Sang Soo; Kim, Ji-Hae; Hong, Sungdo David; Paik, Kyung Hoon; Oh, Yoo Joung; Kim, An Hee; Kwon, Eun Kyung; Choe, Yon Ho

2006-07-01

Prader-Willi syndrome (PWS) is a genetic disorder caused by the nonexpression of paternal genes in the PWS region of chromosome 15q11-13 and is the most common cause of human syndromic obesity. We investigated regional brain metabolic impairment in children with PWS by 18F-FDG PET. Sixteen children with PWS (9 males, 7 females; mean age +/- SD, 4.2 +/- 1.1 y) and 7 healthy children (4 males, 3 females; mean age +/- SD, 4.0 +/- 1.7 y) underwent brain 18F-FDG PET in the resting state. The images of PWS children were compared using statistical parametric mapping analysis with those of healthy children in a voxelwise manner. Group comparison showed that children with PWS had decreased glucose metabolism in the right superior temporal gyrus and left cerebellar vermis, regions that are associated with taste perception/food reward and cognitive and emotional function, respectively. Metabolism was increased in the right orbitofrontal, bilateral middle frontal, right inferior frontal, left superior frontal, and bilateral anterior cingulate gyri, right temporal pole, and left uncus, regions that are involved in cognitive functions related to eating or obsessive-compulsive behavior. Interestingly, no significant metabolic abnormality was found in the hypothalamus, the brain region believed to be most involved in energy intake and expenditure. This study describes the neural substrate underlying the abnormal eating behavior and psychobehavioral problems of PWS.

Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders.

PubMed

Menale, Ciro; Piccolo, Maria Teresa; Cirillo, Grazia; Calogero, Raffaele A; Papparella, Alfonso; Mita, Luigi; Del Giudice, Emanuele Miraglia; Diano, Nadia; Crispi, Stefania; Mita, Damiano Gustavo

2015-06-01

Bisphenol A (BPA) is a xenobiotic endocrine-disrupting chemical. In vitro and in vivo studies have indicated that BPA alters endocrine-metabolic pathways in adipose tissue, which increases the risk of metabolic disorders and obesity. BPA can affect adipose tissue and increase fat cell numbers or sizes by regulating the expression of the genes that are directly involved in metabolic homeostasis and obesity. Several studies performed in animal models have accounted for an obesogen role of BPA, but its effects on human adipocytes - especially in children - have been poorly investigated. The aim of this study is to understand the molecular mechanisms by which environmentally relevant doses of BPA can interfere with the canonical endocrine function that regulates metabolism in mature human adipocytes from prepubertal, non-obese children. BPA can act as an estrogen agonist or antagonist depending on the physiological context. To identify the molecular signatures associated with metabolism, transcriptional modifications of mature adipocytes from prepubertal children exposed to estrogen were evaluated by means of microarray analysis. The analysis of deregulated genes associated with metabolic disorders allowed us to identify a small group of genes that are expressed in an opposite manner from that of adipocytes treated with BPA. In particular, we found that BPA increases the expression of pro-inflammatory cytokines and the expression of FABP4 and CD36, two genes involved in lipid metabolism. In addition, BPA decreases the expression of PCSK1, a gene involved in insulin production. These results indicate that exposure to BPA may be an important risk factor for developing metabolic disorders that are involved in childhood metabolism dysregulation. © 2015 Society for Endocrinology.

Metabolic disorders and cardiovascular risk in people living with HIV/AIDS without the use of antiretroviral therapy.

PubMed

Raposo, Mariana Amaral; Armiliato, Geyza Nogueira de Almeida; Guimarães, Nathalia Sernizon; Caram, Camila Abrahão; Silveira, Raíssa Domingues de Simoni; Tupinambás, Unaí

2017-01-01

Metabolic disorders in people living with HIV/AIDS (PLH) have been described even before the introduction of antiretroviral (ARV) drugs in the treatment of HIV infection and are risk factors for cardiovascular diseases. Based on this, the purpose of this study was to assess metabolic disorders and cardiovascular risk in PLH before the initiation of antiretroviral treatment (ART). This was a cross-sectional descriptive study of 87 PLH without the use of ART, which was carried out between January and September 2012 at a specialized infectious diseases center in Minas Gerais, Brazil. The main metabolic disorders in the population were low serum levels of HDL-cholesterol, hypertriglyceridemia and abdominal obesity. Dyslipidemia was prevalent in 62.6% of the study population, whereas metabolic syndrome (MS) was prevalent in 11.5% of patients assessed by the International Diabetes Federation (IDF) criteria and 10.8% assessed by the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATPIII) criteria. Regarding cardiovascular risk, 89.7% of the population presented a low coronary risk according to the Framingham Risk Score. A greater proportion of patients diagnosed with MS presented low cardiovascular risk (80% assessed by IDF criteria and 77.8% assessed by NCEP-ATPIII criteria). Metabolic disorders in this population may be due to HIV infection or lifestyle (smoking, sedentary lifestyle and inadequate diet). The introduction of ART can enhance dyslipidemia, increasing cardiovascular risk, especially among those who have classic risks of cardiovascular disease.

Foetoplacental epigenetic changes associated with maternal metabolic dysfunction.

PubMed

Kerr, Bredford; Leiva, Andrea; Farías, Marcelo; Contreras-Duarte, Susana; Toledo, Fernando; Stolzenbach, Francisca; Silva, Luis; Sobrevia, Luis

2018-04-12

Metabolic-related diseases are attributed to a sedentary lifestyle and eating habits, and there is now an increased awareness regarding pregnancy as a preponderant window in the programming of adulthood health and disease. The developing foetus is susceptible to the maternal environment; hence, any unfavourable condition will result in foetal physiological adaptations that could have a permanent impact on its health. Some of these alterations are maintained via epigenetic modifications capable of modifying gene expression in metabolism-related genes. Children born to mothers with dyslipidaemia, pregestational or gestational obesity, and gestational diabetes mellitus, have a predisposition to develop metabolic alterations during adulthood. CpG methylation-associated alterations to the expression of several genes in the human placenta play a crucial role in the mother-to-foetus transfer of nutrients and macromolecules. Identification of epigenetic modifications in metabolism-related tissues of offspring from metabolic-altered pregnancies is essential to obtain insights into foetal programming controlling newborn, childhood, and adult metabolism. This review points out the importance of the foetal milieu in the programming and development of human disease and provides evidence of this being the underlying mechanism for the development of adulthood metabolic disorders in maternal dyslipidaemia, pregestational or gestational obesity, and gestational diabetes mellitus. Copyright © 2018. Published by Elsevier Ltd.

Recent Updates on Peroxisome Proliferator-Activated Receptor δ Agonists for the Treatment of Metabolic Syndrome.

PubMed

Grewal, Ajmer S; Beniwal, Meenu; Pandita, Deepti; Sekhon, Bhupinder S; Lather, Viney

2016-01-01

Metabolic syndrome is a disorder described by reduced insulin sensitivity, overweight, hyperlipidaemia, high blood pressure and myocardial disorders, mainly due to high fat diet and lack of physical activity. The peroxisome proliferator activated receptors (PPARs) are type II nuclear hormone receptors that regulate a number of processes in living systems, such as metabolism of carbohydrates and fatty acids, growth and differentiation of cell, and inflammatory reactions. Alpha, gamma and delta are the three distinct isoforms of PPAR. The stimulation of PPARδ alters body's energy fuel preference from glucose to fat. The PPARδ isoform is expressed ubiquitously in all tissues, especially in those tissues which involved in metabolism of lipids like adipose tissue, liver, kidney, and muscle. Currently, PPARδ is an emerging therapeutic target for the pharmacological therapy of disorders associated with metabolic syndrome. Several PPARδ selective agonists had been reported in last ten years, many of them had been advanced into the late phase of clinical trials such as Endurobol (GW501516). However, no PPARδ agonists are yet approved for human use. The present work had been planned to cover wide variety of PPARδ agonists reported till now along with their potential role to tackle various metabolic disorders. The present review has been planned to focus mainly the most popular PPARδ agonists.

Iron deficiency affects nitrogen metabolism in cucumber (Cucumis sativus L.) plants

PubMed Central

2012-01-01

Background Nitrogen is a principal limiting nutrient in plant growth and development. Among factors that may limit NO3- assimilation, Fe potentially plays a crucial role being a metal cofactor of enzymes of the reductive assimilatory pathway. Very few information is available about the changes of nitrogen metabolism occurring under Fe deficiency in Strategy I plants. The aim of this work was to study how cucumber (Cucumis sativus L.) plants modify their nitrogen metabolism when grown under iron deficiency. Results The activity of enzymes involved in the reductive assimilation of nitrate and the reactions that produce the substrates for the ammonium assimilation both at root and at leaf levels in Fe-deficient cucumber plants were investigated. Under Fe deficiency, only nitrate reductase (EC 1.7.1.1) activity decreased both at the root and leaf level, whilst for glutamine synthetase (EC 6.3.1.2) and glutamate synthase (EC 1.4.1.14) an increase was found. Accordingly, the transcript analysis for these enzymes showed the same behaviour except for root nitrate reductase which increased. Furthermore, it was found that amino acid concentration greatly decreased in Fe-deficient roots, whilst it increased in the corresponding leaves. Moreover, amino acids increased in the xylem sap of Fe-deficient plants. Conclusions The data obtained in this work provided new insights on the responses of plants to Fe deficiency, suggesting that this nutritional disorder differentially affected N metabolism in root and in leaf. Indeed under Fe deficiency, roots respond more efficiently, sustaining the whole plant by furnishing metabolites (i.e. aa, organic acids) to the leaves. PMID:23057967

Role of orexins in the central and peripheral regulation of glucose homeostasis: Evidences & mechanisms.

PubMed

Rani, Monika; Kumar, Raghuvansh; Krishan, Pawan

2018-04-01

Orexins (A & B), neuropeptides of hypothalamic origin, act through G-protein coupled receptors, orexin 1 receptor (OX 1 R) and orexin 2 receptor (OX 2 R). The wide projection of orexin neurons in the hypothalamic region allows them to interact with the other neurons and regulate food intake, emotional status, sleep wake cycle and energy metabolism. The autonomic nervous system plays an important regulatory role in the energy metabolism as well as glucose homeostasis. Orexin neurons are also under the control of GABAergic neurons. Emerging preclinical as well as clinical research has reported the role of orexins in the glucose homeostasis since orexins are involved in hypothalamic metabolism circuitry and also rely on sensing peripheral metabolic signals such as gut, adipose derived and pancreatic peptides. Apart from the hypothalamic origin, integration and control in various physiological functions, peripheral origin in wide organs, raises the possibility of use of orexins as a therapeutic biomarker in the management of metabolic disorders. The present review focuses the central as well as peripheral roles of orexins in the glucose homeostasis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diet and cognition: interplay between cell metabolism and neuronal plasticity.

PubMed

Gomez-Pinilla, Fernando; Tyagi, Ethika

2013-11-01

To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders. Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long-term neuronal plasticity. The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid docosahexenoic acid, disrupting neuronal signaling. Thus, dietary docosahexenoic acid seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation.

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors.

PubMed

Phua, Wendy Wen Ting; Wong, Melissa Xin Yu; Liao, Zehuan; Tan, Nguan Soon

2018-05-10

Skeletal muscle comprises 30⁻40% of the total body mass and plays a central role in energy homeostasis in the body. The deregulation of energy homeostasis is a common underlying characteristic of metabolic syndrome. Over the past decades, peroxisome proliferator-activated receptors (PPARs) have been shown to play critical regulatory roles in skeletal muscle. The three family members of PPAR have overlapping roles that contribute to the myriad of processes in skeletal muscle. This review aims to provide an overview of the functions of different PPAR members in energy homeostasis as well as during skeletal muscle metabolic disorders, with a particular focus on human and relevant mouse model studies.

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors

PubMed Central

Phua, Wendy Wen Ting; Wong, Melissa Xin Yu; Liao, Zehuan

2018-01-01

Skeletal muscle comprises 30–40% of the total body mass and plays a central role in energy homeostasis in the body. The deregulation of energy homeostasis is a common underlying characteristic of metabolic syndrome. Over the past decades, peroxisome proliferator-activated receptors (PPARs) have been shown to play critical regulatory roles in skeletal muscle. The three family members of PPAR have overlapping roles that contribute to the myriad of processes in skeletal muscle. This review aims to provide an overview of the functions of different PPAR members in energy homeostasis as well as during skeletal muscle metabolic disorders, with a particular focus on human and relevant mouse model studies. PMID:29747466

Resveratrol restores the circadian rhythmic disorder of lipid metabolism induced by high-fat diet in mice.

PubMed

Sun, Linjie; Wang, Yan; Song, Yu; Cheng, Xiang-Rong; Xia, Shufang; Rahman, Md Ramim Tanver; Shi, Yonghui; Le, Guowei

2015-02-27

Circadian rhythmic disorders induced by high-fat diet are associated with metabolic diseases. Resveratrol could improve metabolic disorder, but few reports focused on its effects on circadian rhythm disorders in a variety of studies. The aim of the present study was to analyze the potential effects of resveratrol on high-fat diet-induced disorders about the rhythmic expression of clock genes and clock-controlled lipid metabolism. Male C57BL/6 mice were divided into three groups: a standard diet control group (CON), a high-fat diet (HFD) group and HFD supplemented with 0.1% (w/w) resveratrol (RES). The body weight, fasting blood glucose and insulin, plasma lipids and leptin, whole body metabolic status and the expression of clock genes and clock-controlled lipogenic genes were analyzed at four different time points throughout a 24-h cycle (8:00, 14:00, 20:00, 2:00). Resveratrol, being associated with rhythmic restoration of fasting blood glucose and plasma insulin, significantly decreased the body weight in HFD mice after 11 weeks of feeding, as well as ameliorated the rhythmities of plasma leptin, lipid profiles and whole body metabolic status (respiratory exchange ratio, locomotor activity, and heat production). Meanwhile, resveratrol modified the rhythmic expression of clock genes (Clock, Bmal1 and Per2) and clock-controlled lipid metabolism related genes (Sirt1, Pparα, Srebp-1c, Acc1 and Fas). The response pattern of mRNA expression for Acc1 was similar to the plasma triglyceride. All these results indicated that resveratrol reduced lipogenesis and ultimately normalized rhythmic expression of plasma lipids, possibly via its action on clock machinery. Copyright © 2015 Elsevier Inc. All rights reserved.

Weight Gain and Metabolic Effects of Mood Stabilizers and Antipsychotics in Pediatric Bipolar Disorder: A Systematic Review and Pooled Analysis of Short-Term Trials

ERIC Educational Resources Information Center

Correll, Christoph U.

2007-01-01

Objective: To review weight and metabolic effects of mood-stabilizing treatments in pediatric bipolar disorder. Method: Systematic PubMed/Medline search of studies reporting on change in weight and/or glucose/lipid values with mood-stabilizing drugs in at least nine pediatric patients with bipolar disorder. Results: Nineteen studies, including 24…

[Changes in carbohydrate metabolism and insulin resistance in patients with Prader-Willi Syndrome (PWS) under growth hormone therapy].

PubMed

Lämmer, Constanze; Weimann, Edda

2007-02-01

Life expectance and life quality have markedly changed in PWS patients within the last 10-15 years. A strict diet, improved physical activity and an additive growth hormone treatment have led to these changes. Growth hormone therapy decreases body fat and improves final height. But growth hormone also antagonizes insulin and therefore increases the diabetic potential. The purpose of our study was to investigate incidence and multiple dependencies of development of impaired carbohydrate metabolism in patients with PWS under growth hormone therapy and to determine suitable parameters for the work-up. 34 patients with genetically approved PWS have been treated with growth hormone for at least 0.5 years. The mean duration of growth hormone treatment was 2.15 years (0.5-4.51). At the start of growth hormone treatment patients were 1.33 to 16.47 years old. The clinical picture and the nutritional situation of children with PWS change age-dependent and can be divided up into three phases. The patients were duty subdivided into three age-groups at the beginning of growth hormone treatment. Group 1: 15 PWS patients, mean age 2.62 years (1.33-3.78). Group 2: 10 PWS patients, mean age 5.54 years (4.08-7.61). Group 3: 9 PWS patients, mean age 11.35 years (8.89-16.47). Data were collected within 0.3-0.38 years before start of treatment and every 6 months throughout the treatment period. Anthropometrical data, fat mass by bioelectric impedance analysis (BIA), fasting insulin, HbA1c, C-peptide, blood fats and the blood sugar profile in oral glucose tolerance tests (OGT/1.75 g glucose/kg body mass) were obtained. Growth hormone therapy was started with an average dose of 0.031 mg/kg body mass in all groups. Insulin resistance was based on Homeostasis Model Assessment-Test (HOMA). No IR or pathological OGT were detected when growth hormone therapy started before the 4th year of life. When therapy started between the 4th and 8th year, PWS patients with normal weight did not develop an IR under GH therapy. 6% developed a glucose tolerance (IGT) disorder and 4% developed an increased fasting glucose (IFG). 5 of 9 PWS patients older than 8 years at therapystart showed a transient disorder of glucose metabolism: 11% of the results obtained in these patients presented an IR with no pathological OGT, 13% showed an IR with IGT, 7% showed an IR with IFG, and 2% showed an IR with transient diabetes. For 4% the IFG persisted with no IR, for 4% the IGT persisted with no IR. These patients differed from younger ones by an increased average BMI, an increase fat body ratio and an increase fasting insulin as well as an already reached puberty. No difference was found in C-peptide, HbA1c or GH dose/kg/body mass. Transient glucose metabolism disorders with no development of manifest insulin resistance are shown by PWS patients with normal weight starting from 4th year under GH therapy. Changes in the glucose metabolism with and with no development of IR appear after start of puberty and weight increase. Changes persisted partially for 18 months. GH therapy was not interrupted for any patient, whereby physical training and dietetic measurements were increased for all patients. HOMA-index and OGT shall be used in parallel to monitor glucose metabolism as both show independently distinctive features. HbA1c and C-peptide are not suitable parameters for monitoring carbohydrate metabolism in PWS patients under GH treatment.

Food for thought: the role of appetitive peptides in age-related cognitive decline.

PubMed

Fadel, Jim R; Jolivalt, Corinne G; Reagan, Lawrence P

2013-06-01

Through their well described actions in the hypothalamus, appetitive peptides such as insulin, orexin and leptin are recognized as important regulators of food intake, body weight and body composition. Beyond these metabolic activities, these peptides also are critically involved in a wide variety of activities ranging from modulation of immune and neuroendocrine function to addictive behaviors and reproduction. The neurological activities of insulin, orexin and leptin also include facilitation of hippocampal synaptic plasticity and enhancement of cognitive performance. While patients with metabolic disorders such as obesity and diabetes have greater risk of developing cognitive deficits, dementia and Alzheimer's disease (AD), the underlying mechanisms that are responsible for, or contribute to, age-related cognitive decline are poorly understood. In view of the importance of these peptides in metabolic disorders, it is not surprising that there is a greater focus on their potential role in cognitive deficits associated with aging. The goal of this review is to describe the evidence from clinical and pre-clinical studies implicating insulin, orexin and leptin in the etiology and progression of age-related cognitive decline. Collectively, these studies support the hypothesis that leptin and insulin resistance, concepts normally associated with the hypothalamus, are also applicable to the hippocampus. Copyright © 2013 Elsevier B.V. All rights reserved.

From "Kidneys Govern Bones" to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science.

PubMed

Wang, Xiao-Qin; Zou, Xin-Rong; Zhang, Yuan Clare

2016-01-01

Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes.

Erythropoietin and diabetes mellitus

PubMed Central

Maiese, Kenneth

2015-01-01

Erythropoietin (EPO) is a 30.4 kDa growth factor and cytokine that governs cell proliferation, immune modulation, metabolic homeostasis, vascular function, and cytoprotection. EPO is under investigation for the treatment of variety of diseases, but appears especially suited for the treatment of disorders of metabolism that include diabetes mellitus (DM). DM and the complications of this disease impact a significant portion of the global population leading to disability and death with currently limited therapeutic options. In addition to its utility for the treatment of anemia, EPO can improve cardiac function, reduce fatigue, and improve cognition in patients with DM as well as regulate cellular energy metabolism, obesity, tissue repair and regeneration, apoptosis, and autophagy in experimental models of DM. Yet, EPO can have adverse effects that involve the vasculature system and unchecked cellular proliferation. Critical to the cytoprotective capacity and the potential for a positive clinical outcome with EPO are the control of signal transduction pathways that include protein kinase B, the mechanistic target of rapamycin, Wnt signaling, mammalian forkhead transcription factors of the O class, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae), and AMP activated protein kinase. Therapeutic strategies that can specifically target and control EPO and its signaling pathways hold great promise for the development of new and effective clinical treatments for DM and the complications of this disorder. PMID:26516410

Assessment of metabolic status in young Japanese females using postprandial glucose and insulin levels

PubMed Central

Sakuma, Masae; Sasaki, Megumi; Katsuda, Sayaka; Kobayashi, Kana; Takaya, Chiaki; Umeda, Minako; Arai, Hidekazu

2014-01-01

Lifestyle-related diseases develop through the accumulation of undesirable lifestyle habits both prior to the onset of disease as well as during normal healthy life. Accordingly, early detection of, and intervention in, metabolic disorders is desirable, but is hampered by the lack of an established evaluation index for young individuals. The purpose of this study was to investigate the utility of a biomarker of health in young female subjects. The subjects were young healthy Japanese females in whom energy expenditure was measured for a period of 210 min after a test meal. In addition, Δplasma glucose and Δserum insulin were calculated from the fasting and 30 min values. ΔPlasma glucose and Δserum insulin levels varied widely compared to fasting levels. Both the area under the curve of carbohydrate oxidation rate and serum free fatty acid levels were higher in individuals in the high Δplasma glucose group. Moreover, Δplasma glucose was higher in individuals in the high Δserum insulin group than in the low Δserum insulin group. We conclude that nutritional balanced liquid loading test using Δplasma glucose and Δserum insulin as the evaluation index is useful for the detection of primary metabolic disorders in young females. PMID:24895484

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives.

PubMed

Lamonaca, Palma; Prinzi, Giulia; Kisialiou, Aliaksei; Cardaci, Vittorio; Fini, Massimo; Russo, Patrizia

2017-03-20

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI).

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

PubMed

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

2016-03-01

Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility disorders were those between BCS and MET in both first and later lactations. Results indicated a limited value of a joint genetic evaluation model for metabolic disease traits and fertility disorders in Canadian Holsteins. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Neuroimaging Insights into the Pathophysiology of Sleep Disorders

PubMed Central

Desseilles, Martin; Dang-Vu, Thanh; Schabus, Manuel; Sterpenich, Virginie; Maquet, Pierre; Schwartz, Sophie

2008-01-01

Neuroimaging methods can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. However, it is still unclear how these new data might improve our understanding of the pathophysiology underlying adult sleep disorders. Here we review functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). The studies reviewed include neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy), metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging), and ligand marker measurements. Based on the current state of the research, we suggest that brain imaging is a useful approach to assess the structural and functional correlates of sleep impairments as well as better understand the cerebral consequences of various therapeutic approaches. Modern neuroimaging techniques therefore provide a valuable tool to gain insight into possible pathophysiological mechanisms of sleep disorders in adult humans. Citation: Desseilles M; Dang-Vu TD; Schabus M; Sterpenich V; Maquet P; Schwartz S. Neuroimaging insights into the pathophysiology of sleep disorders. SLEEP 2008;31(6):777–794. PMID:18548822

Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part I. Metabolic and digestive disorders.

PubMed

Stangaferro, M L; Wijma, R; Caixeta, L S; Al-Abri, M A; Giordano, J O

2016-09-01

The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metabolic and digestive disorders-including displaced abomasum, ketosis, and indigestion-based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of the disorders by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. A HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as a HIS of <86 during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, β-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The sensitivity of the HIS was 98% [95% confidence interval (CI): 93, 100] for displaced abomasum (n=41); 91% (95% CI: 83, 99) for ketosis (n=54); 89% (95% CI: 68, 100) for indigestion (n=9); and 93% (95% CI: 89, 98) for all metabolic and digestive disorders combined (n=104). Days (mean and 95% CI) from the first positive HIS <86 and CD were -3 (-3.7, -2.3), -1.6 (-2.3, -1.0), -0.5 (-1.5, 0.5), and -2.1 (-2.5, -1.6) for displaced abomasum, ketosis, indigestion, and all metabolic and digestive disorders, respectively. The patterns of rumination, activity, and HIS for cows flagged by the AHMS were characterized by lower levels than for cows without a health disorder and cows not flagged by the AHMS from -5 to 5 d after CD, depending on the disorder and parameter. Differences between cows without health disorders and those flagged by the AHMS for blood markers of metabolic and health status confirmed the observations of the CD and AHMS alerts. The overall sensitivity and timing of the AHMS alerts for cows with metabolic and digestive disorders indicated that AHMS that combine rumination and activity could be a useful tool for identifying cows with metabolic and digestive disorders. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION.

ERIC Educational Resources Information Center

CENTERWALL, WILLARD R.; CENTERWALL, SIEGRIED A.

ADDRESSED TO PUBLIC HEALTH WORKERS AND PHYSICIANS IN GENERAL PRACTICE, THE PAMPHLET INTRODUCES METHODS OF DETECTING AND MANAGING PHENYLKETONURIA, AN INHERITED METABOLIC DISORDER ASSOCIATED WITH MENTAL RETARDATION. INFORMATION, UPDATED FROM THE 1961 EDITION, IS INCLUDED ON THE INCIDENCE AND GENETICS, BIOCHEMISTRY, AND CLINICAL COURSE OF THE…

Drug correction of behavioral reactions and metabolic disorders in rats with craniocerebral trauma.

PubMed

Zarubina, I V

2003-07-01

Intraperitoneal injection of bemithyl in a dose of 25 mg/kg for 3 days after craniocerebral injury reduced psychopathological symptoms in rats with different resistance to acute hypoxia, restored the structure of individual behavior, and prevented metabolic disorders in the brain.

The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome

PubMed Central

Putnam, Kelly; Shoemaker, Robin; Yiannikouris, Frederique

2012-01-01

The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment. PMID:22227126

Adipocytes properties and crosstalk with immune system in obesity-related inflammation.

PubMed

Maurizi, Giulia; Della Guardia, Lucio; Maurizi, Angela; Poloni, Antonella

2018-01-01

Obesity is a condition likely associated with several dysmetabolic conditions or worsening of cardiovascular and other chronic disturbances. A key role in this mechanism seem to be played by the onset of low-grade systemic inflammation, highlighting the importance of the interplay between adipocytes and immune system cells. Adipocytes express a complex and highly adaptive biological profile being capable to selectively activate different metabolic pathways in order to respond to environmental stimuli. It has been demonstrated how adipocytes, under appropriate stimulation, can easily differentiate and de-differentiate thereby converting themselves into different phenotypes according to metabolic necessities. Although underlying mechanisms are not fully understood, growing in adipocyte size and the inability of storing triglycerides under overfeeding conditions seem to be crucial for the switching to a dysfunctional metabolic profile, which is characterized by inflammatory and apoptotic pathways activation, and by the shifting to pro-inflammatory adipokines secretion. In obesity, changes in adipokines secretion along with adipocyte deregulation and fatty acids release into circulation contribute to maintain immune cells activation as well as their infiltration into regulatory organs. Over the well-established role of macrophages, recent findings suggest the involvement of new classes of immune cells such as T regulatory lymphocytes and neutrophils in the development inflammation and multi systemic worsening. Deeply understanding the pathways of adipocyte regulation and the de-differentiation process could be extremely useful for developing novel strategies aimed at curbing obesity-related inflammation and related metabolic disorders. © 2017 Wiley Periodicals, Inc.

Genome-wide association studies for the identification of biomarkers in metabolic diseases.

PubMed

Pattin, Kristine A; Moore, Jason H

2010-01-01

The field of genetics as it relates to metabolic disorders such as obesity and type II diabetes is complicated, and along with the medical research community, great strides are being taken to begin to understand the biological and genetic underpinnings of these diseases, with the hope of improving therapeutic, diagnostic and preventive strategies. Although research on metabolic disorders has been continuing for decades, the completion of the Human Genome Project in 2003 and the International HapMap Project in 2005 gave rise to an abundance of research tools, such as genome-wide genotyping, which allow researchers to conduct genome-wide association studies (GWAS) for detecting genetic variants that confer increased or decreased susceptibility to such complex diseases. In this review, the complex nature of metabolic disorders is discussed, specifically obesity and type II diabetes, as well as the limitations of the GWAS as applied to these disorders. While acknowledging limitations of GWAS, it is hoped to provide an insight about how GWAS can be adapted and advantageous in the clinical setting, enhancing prevention, diagnosis and treatment of these diseases. To be able to use the GWAS in a clinical setting is a complex challenge, yet it is hoped that in the future this tool will ultimately allow the development of pharmaceutical options that are capable of targeting the cause of metabolic disorders, not just the symptoms themselves.

Genetic linkage study of bipolar disorder and the serotonin transporter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelsoe, J.R.; Morison, M.; Mroczkowski-Parker, Z.

1996-04-09

The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Oldmore » Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter. 20 refs., 2 tabs.« less

Umbilical Cord Blood Transplantation From Unrelated Donors

ClinicalTrials.gov

2018-02-17

Acute Leukemia; Immune Deficiency Disorder; Congenital Hematological Disorder; Metabolism Disorder; Aplastic Anemia; Myelodysplastic Syndromes; Chronic Leukemia; Lymphoma; Multiple Myeloma; Solid Tumor

Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice.

PubMed

Otsuka, Tsuyoshi; Kawai, Misato; Togo, Yuki; Goda, Ryosei; Kawase, Takahiro; Matsuo, Haruka; Iwamoto, Ayaka; Nagasawa, Mao; Furuse, Mitsuhiro; Yasuo, Shinobu

2014-02-01

Seasonal affective disorder (SAD) is characterized by depression during specific seasons, generally winter. The pathophysiological mechanisms underlying SAD remain elusive due to a limited number of animal models with high availability and validity. Here we show that laboratory C57BL/6J mice display photoperiodic changes in depression-like behavior and brain serotonin content. C57BL/6J mice maintained under short-day conditions, as compared to those under long-day conditions, demonstrated prolonged immobility times in the forced swimming test with lower brain levels of serotonin and its precursor l-tryptophan. Furthermore, photoperiod altered multiple parameters reflective of peripheral metabolism, including the ratio of plasma l-tryptophan to the sum of other large neutral amino acids that compete for transport across the blood-brain barrier, responses of circulating glucose and insulin to glucose load, sucrose intake under restricted feeding condition, and sensitivity of the brain serotonergic system to peripherally administered glucose. These data suggest that the mechanisms underlying SAD involve the brain-peripheral tissue network, and C57BL/6J mice can serve as a powerful tool for investigating the link between seasons and mood. Copyright © 2013 Elsevier Ltd. All rights reserved.

Histochemical stains as promising means for the laser histochemical surgery of a number of pathologies

NASA Astrophysics Data System (ADS)

Piruzyan, L. A.; Mikhailovskiy, Ye. M.; Piruzyan, A. L.

1999-12-01

The directions of laboratory and clinical studies oriented to experimental confirmation of the priority concept of `laser histochemical surgery' are presented. The goal of the studies is reproduction on experimental model of a number of pathologies (in vivo and in vitro) of the `sensitization to laser radiation by staining' effect. Testing of the histochemical stains as sensitizers to laser irradiation of their `address substrates', i.e. vitally stained intracellular structures which participate in the pathologic processes evolution is under planning. The processes include: (a) metabolic disorders in the brain cells, i.e. disseminated sclerosis; (b) generalized metabolic disorders- -mucopolysaccharidosis and collagenosises (periarteritis nodosa, rheumatism, rheumatoid arthritis, sclerodermia); (3) metabolic disorders in individual organs--vessel atherosclerosis, hypercholesterolemia, myocardial infarction, cardiosclerosis, caries and parodontosis. The conditions of the studies are detailed in the recommendations along the positions: (1) disease name; (2) disease characteristics: (a) pathomorphologic, (b) biochemical; (3) stains revealing the disease signs and recommended for testing; (4) `address substrates' of the stains that are targets for laser radiation; (5) lasers recommended for the testing after the cells staining in vivo in the corresponding pathology; (6) experimental models of the pathologies suggested for the testing; (7) criteria of the stain efficiency as target sensitizer to the laser light (criteria of the `laser sensitization by staining' efficiency). Possible perspectives for the experimental clinical medicine are indicated of common histochemical stains and lasers use and of practice introduction of the `laser histochemical surgery' in the case the described concept is confirmed in experiments and clinically.

TRUSS exacerbates NAFLD development by promoting IκBα degradation.

PubMed

Yu, Chang-Jiang; Wang, Qiu-Shi; Wu, Ming-Ming; Song, Bin-Lin; Liang, Chen; Lou, Jie; Tang, Liang-Liang; Yu, Xiao-Di; Niu, Na; Yang, Xu; Zhang, Bao-Long; Qu, Yao; Liu, Yang; Dong, Zhi-Chao; Zhang, Zhi-Ren

2018-04-27

There is no effective treatment method for non-alcoholic fatty liver disease (NAFLD), the most common liver disease. The exact mechanism underlying the pathogenesis of NAFLD remains to be elucidated. Here, we report that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS) acts as a positive regulator of NAFLD and in a variety of metabolic disorders. TRUSS expression was respectively increased in the human liver specimens with NAFLD or non-alcoholic steatohepatitis (NASH), and in the livers of high-fat diet (HFD)-induced and genetically obese (ob/ob) mice. Conditional knockout of TRUSS in hepatocytes significantly ameliorated hepatic steatosis, insulin resistance (IR), glucose intolerance, and inflammatory responses in mice after HFD challenge or in spontaneous obese mice with normal chow (NC) feeding. All these HFD-induced pathological phenotypes were exacerbated in mice overexpressing TRUSS in hepatocytes. We show that TRUSS physically interacts with IκBα and promotes the ubiquitination and degradation of IκBα, which leading to aberrant activation of NF-κB. Overexpressing IκBα S32A/S36A , a phosphorylation-resistant mutant of IκBα, in the hepatocyte-specific TRUSS overexpressing mice almost abolished HFD-induced NAFLD and metabolic disorders. Hepatocyte TRUSS promotes pathological stimuli-induced NAFLD and metabolic disorders, via activation of NF-κB by promoting ubiquitination and degradation of IκBα. Our findings may provide a novel strategy for prevention and treatment of NAFLD by targeting TRUSS. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

PubMed Central

Marini, Francesca; Cianferotti, Luisella; Brandi, Maria Luisa

2016-01-01

Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2), the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs). Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine’s principles. PMID:27529237

Blueberries and Metabolic Syndrome

USDA-ARS?s Scientific Manuscript database

Metabolic Syndrome is a cluster of metabolic disorders that increase the risk of cardiovascular diseases. Type 2 diabetes, elevated blood pressure, and atherogenic dyslipidemia are among the metabolic alterations that predispose the individual to several adverse cardiovascular complications. The hea...

The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders

PubMed Central

Stafstrom, Carl E.; Rho, Jong M.

2012-01-01

Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more “natural” treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component. PMID:22509165

Impact of Gut Microbiota on Obesity, Diabetes, and Cardiovascular Disease Risk.

PubMed

Miele, Luca; Giorgio, Valentina; Alberelli, Maria Adele; De Candia, Erica; Gasbarrini, Antonio; Grieco, Antonio

2015-12-01

Gut microbiota has been recently established to have a contributory role in the development of cardiometabolic disorders, such as atherosclerosis, obesity, and type 2 diabetes. Growing interest has focused on the modulation of gut microbiota as a therapeutic strategy in cardiovascular diseases and metabolic disorders. In this paper, we have reviewed the impact of gut microbiota on metabolic disorders and cardiovascular disease risk, focusing on the newest findings in this field.

[Principles of changes of structural organization of cell membranes and functional properties of erythrocytes in neurotic disorders].

PubMed

Riazantseva, N V; Novitskiĭ, V V

2003-02-01

Investigation into structural, metabolic, and functional conditions of red blood cells was performed in 24 patients with a neurosis (neurasthenia, disturbance of asaptation) with the aid of electrophoretic division of proteins of the erythrocyte membrane, thin-layer chromatography, fluorescent probing of membranes, evaluation of peroxidative oxidation process, scanning and transmission electron microscopy, laser diphractometry, photometry. The patients with neurotic disorders at the early period after the influence of psychogenic factors (up to 3 months) revealed disorganization of lipid and protein composition of the red cell membrane, increase in microviscosity of its lipid phase, impairment of surface architectonics and ultrastructure of red cells, decrease of a deformation ability and increase of aggregate properties of erythrocytes. The authors treat stability of erythrocytes' homeostasis under the long-term influence of psychogenic factors from a viewpoint of adaptive changes in organism under the influence of neurogenic factors.

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

PubMed Central

Stankiewicz, James; Panter, Scott S; Neema, Mohit; Arora, Ashish; Batt, Courtney; Bakshi, Rohit

2007-01-01

Summary Iron is important for brain oxygen transport, electron transfer, neurotransmitter synthesis, and myelin production. Though iron deposition has been observed in the brain with normal aging, increased iron has also been shown in many chronic neurologic disorders including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. In vitro studies have demonstrated that excessive iron can lead to free radical production, which can promote neurotoxicity. However, the link between observed iron deposition and pathologic processes underlying various diseases of the brain is not well understood. It is not known whether excessive in vivo iron directly contributes to tissue damage or is solely an epiphenomenon. In this article we focus on the imaging of brain iron and the underlying physiology and metabolism relating to iron deposition. We conclude with a discussion of the potential implications of iron-related toxicity to neurotherapeutic development. PMID:17599703

[Pediatric neurotransmitter disease in Japan].

PubMed

Shintaku, Haruo

2012-09-01

Pediatric neurotransmitter disease (PND) encompasses a range of rare genetic disorders that affect the metabolism of neurotransmitters in children. While these neurological disorders are often studied independently of each other, they all manifest central nervous system symptoms and require proper diagnosis and intervention at early stages. Since clinical symptoms of PND can be nonspecific, the conditions are often under-diagnosed, leaving patients without a chance to receive effective treatment. Envisioning PND as a whole, a comprehensive research effort is underway for a better understanding of pathophysiology and epidemiology in Japan, and toward the establishment of diagnostic criteria. The early diagnosis and development of new effective therapies are of urgent importance for these rare disorders that are not covered by newborn mass screening. For rarer forms of PND, at the same time, it is important to encourage recognition and understanding of the disease concept among healthcare professionals.

Deconstructing Black Swans: An Introductory Approach to Inherited Metabolic Disorders in the Neonate.

PubMed

Mew, Nicholas Ah; Viall, Sarah; Kirmse, Brian; Chapman, Kimberly A

2015-08-01

Inherited metabolic disorders (IMDs) are individually rare but collectively common disorders that frequently require rapid or urgent therapy. This article provides a generalized approach to IMDs, as well as some investigations and safe therapies that may be initiated pending the metabolic consult. An overview of the research supporting management strategies is provided. In addition, the newborn metabolic screen is reviewed. Caring for infants with IMDs can seem difficult because each of the types is rarely seen; however, collectively the management can be seen as similar. When an IMD is suspected, a metabolic specialist should be consulted for expert advice regarding appropriate laboratory investigations and management. Because rapid intervention of IMDs before the onset of symptoms may prevent future irreversible sequelae, each abnormal newborn screen must be addressed promptly. Management can be difficult. Research in this area is limited and can be difficult without multisite coordination since sample sizes of any significance are difficult to achieve.

Short-term feeding at the wrong time is sufficient to desynchronize peripheral clocks and induce obesity with hyperphagia, physical inactivity and metabolic disorders in mice.

PubMed

Yasumoto, Yuki; Hashimoto, Chiaki; Nakao, Reiko; Yamazaki, Haruka; Hiroyama, Hanako; Nemoto, Tadashi; Yamamoto, Saori; Sakurai, Mutsumi; Oike, Hideaki; Wada, Naoyuki; Yoshida-Noro, Chikako; Oishi, Katsutaka

2016-05-01

The circadian clock regulates various physiological and behavioral rhythms such as feeding and locomotor activity. Feeding at unusual times of the day (inactive phase) is thought to be associated with obesity and metabolic disorders in experimental animals and in humans. The present study aimed to determine the underlying mechanisms through which time-of-day-dependent feeding influences metabolic homeostasis. We compared food consumption, wheel-running activity, core body temperature, hormonal and metabolic variables in blood, lipid accumulation in the liver, circadian expression of clock and metabolic genes in peripheral tissues, and body weight gain between mice fed only during the sleep phase (DF, daytime feeding) and those fed only during the active phase (NF, nighttime feeding). All mice were fed with the same high-fat high-sucrose diet throughout the experiment. To the best of our knowledge, this is the first study to examine the metabolic effects of time-imposed restricted feeding (RF) in mice with free access to a running wheel. After one week of RF, DF mice gained more weight and developed hyperphagia, higher feed efficiency and more adiposity than NF mice. The daily amount of running on the wheel was rapidly and obviously reduced by DF, which might have been the result of time-of-day-dependent hypothermia. The amount of daily food consumption and hypothalamic mRNA expression of orexigenic neuropeptide Y and agouti-related protein were significantly higher in DF, than in NF mice, although levels of plasma leptin that fluctuate in an RF-dependent circadian manner, were significantly higher in DF mice. These findings suggested that the DF induced leptin resistance. The circadian phases of plasma insulin and ghrelin were synchronized to RF, although the corticosterone phase was unaffected. Peak levels of plasma insulin were remarkably higher in DF mice, although HOMA-IR was identical between the two groups. Significantly more free fatty acids, triglycerides and cholesterol accumulated in the livers of DF, than NF mice, which resulted from the increased expression of lipogenic genes such as Scd1, Acaca, and Fasn. Temporal expression of circadian clock genes became synchronized to RF in the liver but not in skeletal muscle, suggesting that uncoupling metabolic rhythms between the liver and skeletal muscle also contribute to DF-induced adiposity. Feeding at an unusual time of day (inactive phase) desynchronizes peripheral clocks and causes obesity and metabolic disorders by inducing leptin resistance, hyperphagia, physical inactivity, hepatic fat accumulation and adiposity. Copyright © 2016 Elsevier Inc. All rights reserved.

Relative variations of gut microbiota in disordered cholesterol metabolism caused by high-cholesterol diet and host genetics.

PubMed

Bo, Tao; Shao, Shanshan; Wu, Dongming; Niu, Shaona; Zhao, Jiajun; Gao, Ling

2017-08-01

Recent studies performed provide mechanistic insight into effects of the microbiota on cholesterol metabolism, but less focus was given to how cholesterol impacts the gut microbiota. In this study, ApoE -/- Sprague Dawley (SD) rats and their wild-type counterparts (n = 12) were, respectively, allocated for two dietary condition groups (normal chow and high-cholesterol diet). Total 16S rDNA of fecal samples were extracted and sequenced by high-throughput sequencing to determine differences in microbiome composition. Data were collected and performed diversity analysis and phylogenetic analysis. The influence of cholesterol on gut microbiota was discussed by using cholesterol dietary treatment as exogenous cholesterol disorder factor and genetic modification as endogenous metabolic disorder factor. Relative microbial variations were compared to illustrate the causality and correlation of cholesterol and gut microbiota. It turned out comparing to genetically modified rats, exogenous cholesterol intake may play more effective role in changing gut microbiota profile, although the serum cholesterol level of genetically modified rats was even higher. Relative abundance of some representative species showed that the discrepancies due to dietary variation were more obvious, whereas some low abundance species changed because of genetic disorders. Our results partially demonstrated that gut microbiota are relatively more sensitive to dietary variation. Nevertheless, considering the important effect of bacteria in cholesterol metabolism, the influence to gut flora by "genetically caused cholesterol disorder" cannot be overlooked. Manipulation of gut microbiota might be an effective target for preventing cholesterol-related metabolic disorders. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Metabolomics differences between silkworms (Bombyx mori) reared on fresh mulberry (Morus) leaves or artificial diets.

PubMed

Dong, Hui-Ling; Zhang, Sheng-Xiang; Tao, Hui; Chen, Zhuo-Hua; Li, Xue; Qiu, Jian-Feng; Cui, Wen-Zhao; Sima, Yang-Hu; Cui, Wei-Zheng; Xu, Shi-Qing

2017-09-08

Silkworms (Bombyx mori) reared on artificial diets have great potential applications in sericulture. However, the mechanisms underlying the enhancement of metabolic utilization by altering silkworm nutrition are unclear. The aim of this study was to investigate the mechanisms responsible for the poor development and low silk protein synthesis efficiency of silkworms fed artificial diets. After multi-generational selection of the ingestive behavior of silkworms to artificial diets, we obtained two strains, one of which developed well and another in which almost all its larvae starved to death on the artificial diets. Subsequently, we analyzed the metabolomics of larval hemolymph by gas chromatography/liquid chromatography-mass spectrometry, and the results showed that vitamins were in critically short supply, whereas the nitrogen metabolic end product of urea and uric acid were enriched substantially, in the hemolymph of the silkworms reared on the artificial diets. Meanwhile, amino acid metabolic disorders, as well as downregulation of carbohydrate metabolism, energy metabolism, and lipid metabolism, co-occurred. Furthermore, 10 male-dominant metabolites and 27 diet-related metabolites that differed between male and female silkworms were identified. These findings provide important insights into the regulation of silkworm metabolism and silk protein synthesis when silkworms adapt to an artificial diet.

Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism

PubMed Central

Bruce, Kimberley D.; Zsombok, Andrea; Eckel, Robert H.

2017-01-01

Metabolic disorders, particularly aberrations in lipid homeostasis, such as obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest together as the metabolic syndrome (MetS). Despite major advances in our understanding of the pathogenesis of these disorders, the prevalence of the MetS continues to rise. It is becoming increasingly apparent that intermediary metabolism within the central nervous system is a major contributor to the regulation of systemic metabolism. In particular, lipid metabolism within the brain is tightly regulated to maintain neuronal structure and function and may signal nutrient status to modulate metabolism in key peripheral tissues such as the liver. There is now a growing body of evidence to suggest that fatty acid (FA) sensing in hypothalamic neurons via accumulation of FAs or FA metabolites may signal nutritional sufficiency and may decrease hepatic glucose production, lipogenesis, and VLDL-TG secretion. In addition, recent studies have highlighted the existence of liver-related neurons that have the potential to direct such signals through parasympathetic and sympathetic nervous system activity. However, to date whether these liver-related neurons are FA sensitive remain to be determined. The findings discussed in this review underscore the importance of the autonomic nervous system in the regulation of systemic metabolism and highlight the need for further research to determine the key features of FA neurons, which may serve as novel therapeutic targets for the treatment of metabolic disorders. PMID:28421037

Dynapenic obesity as an associated factor to lipid and glucose metabolism disorders and metabolic syndrome in older adults - Findings from SABE Study.

PubMed

Alexandre, Tiago da Silva; Aubertin-Leheudre, Mylène; Carvalho, Lívia Pinheiro; Máximo, Roberta de Oliveira; Corona, Ligiana Pires; Brito, Tábatta Renata Pereira de; Nunes, Daniella Pires; Santos, Jair Licio Ferreira; Duarte, Yeda Aparecida de Oliveira; Lebrão, Maria Lúcia

2018-08-01

There is little evidence showing that dynapenic obesity is associated with lipid and glucose metabolism disorders, high blood pressure, chronic disease and metabolic syndrome. Our aim was to analyze whether dynapenic abdominal obesity can be associated with lipid and glucose metabolism disorders, high blood pressure, metabolic syndrome and cardiovascular diseases in older adults living in São Paulo. This cross-sectional study included 833 older adults who took part of the third wave of the Health, Well-being and Aging Study in 2010. Based on waist circumference (>88 cm women and >102 cm men) and handgrip strength (<16 kg women and <26 kg men), four groups were identified: non-dynapenic/non-abdominal obese (ND/NAO), abdominal obese alone (AOA), dynapenic alone (DA) and dynapenic/abdominal obese (D/AO). Dependent variables were blood pressure, lipid profile, fasting glucose and glycated-haemoglobin, metabolic syndrome and cardiovascular diseases. Logistic regression was used to analyze the associations between dynapenia and abdominal obesity status and lipid and glucose metabolic profiles, blood pressure, cardiovascular diseases and metabolic syndrome. The fully adjusted models showed that D/AO individuals had higher prevalence of low HDL plasma concentrations (OR = 2.51, 95%CI: 1.40-4.48), hypertriglyceridemia (OR = 2.53, 95%CI: 1.43-4.47), hyperglycemia (OR = 2.05, 95%CI: 1.14-3.69), high glycated-haemoglobin concentrations (OR = 1.84, 95%CI: 1.03-3.30) and metabolic syndrome (OR = 12.39, 95%CI: 7.38-20.79) than ND/NAO. Dynapenic and D/AO individuals had higher prevalence of heart disease (OR = 2.05, 95%CI: 1.17-3.59 and OR = 1.92, 95%CI: 1.06-3.48, respectively) than ND/NAO. D/AO was associated with high prevalence of lipid and glucose metabolism disorders and metabolic syndrome while dynapenia and D/AO were associated with high prevalence of heart disease. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Making the invisible visible.

PubMed

van Steensel, Maurice A M

2016-04-01

In this review, I will discuss how careful scrutiny of genetic skin disorders could help us to understand human biology. Like other organs, the skin and its appendages, such as hairs and teeth, experience fundamental biological processes ranging from lipid metabolism to vesicular transport and cellular migration. However, in contrast to other organ systems, they are accessible and can be studied with relative ease. By visually revealing the functional consequences of single gene defects, genetic skin diseases offer a unique opportunity to study human biology. Here, I will illustrate this concept by discussing how human genetic disorders of skin pigmentation reflect the mechanisms underlying this complex and vital process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomarkers in Autism

PubMed Central

Goldani, Andre A. S.; Downs, Susan R.; Widjaja, Felicia; Lawton, Brittany; Hendren, Robert L.

2014-01-01

Autism spectrum disorders (ASDs) are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression, and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers. PMID:25161627

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

PubMed

Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

PubMed Central

Zhong, Hong; Ma, Minjuan

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction. PMID:29484304

Microbial contributions to chronic inflammation and metabolic disease.

PubMed

Shanahan, Fergus; Sheehan, Donal

2016-07-01

It is long known that immune and metabolic cascades intersect at various cross-points. More recently, the regulatory influence of the microbiota on both of these cascades has emerged. Advances with therapeutic implications for chronic immunologic and metabolic disorders are examined. Disturbances of the microbiota, particularly in early life, may be the proximate environmental risk factor in socioeconomically developed societies for development of chronic immune-allergic and metabolic disorders, including obesity. Antibiotics and dietary factors contribute to this risk. Multiple microbial signalling molecules mediate host-microbe interactions including bacterial metabolites such as short-chain fatty acids, bile salts and others. New strategies for manipulating the composition and metabolic activity of the gut microbiota have emerged and offer a realistic prospect of personalized therapeutic options in immune and metabolic diseases.

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

PubMed

Lorenz, Carmen; Prigione, Alessandro

2017-12-01

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

Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents.

PubMed

Juárez-López, Carlos; Klünder-Klünder, Miguel; Medina-Bravo, Patricia; Madrigal-Azcárate, Adrián; Mass-Díaz, Eliezer; Flores-Huerta, Samuel

2010-06-07

Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents. An analytical, cross-sectional and population-based study was performed in forty-four public primary schools in Campeche City, Mexico. A total of 466 obese children and adolescents between 11-13 years of age were recruited. Fasting glucose and insulin concentrations, high density lipoprotein cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressures were measured; insulin resistance and metabolic syndrome were also evaluated. Out of the total population studied, 69% presented low values of high density lipoprotein cholesterol, 49% suffered from abdominal obesity, 29% had hypertriglyceridemia, 8% presented high systolic and 13% high diastolic blood pressure, 4% showed impaired fasting glucose, 51% presented insulin resistance and 20% metabolic syndrome. In spite of being obese, 13% of the investigated population did not present any metabolic disorder. For each one of the components of the metabolic syndrome, when insulin resistance increased so did odds ratios as cardiometabolic risk factors. Regardless of age and gender an increased degree of insulin resistance is associated with a higher prevalence of disorders in each of the components of the metabolic syndrome and with a heightened risk of suffering metabolic syndrome among obese children and adolescents.

ATOMIC ENERGY COMMISSION PROGRESS REPORT ON BONE RESEARCH , 1960-1961

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1962-10-31

A review of osteoporosis concepts is presented. Activities in an experimental program to study osteoporosis by examining mineral metabolism in bone and by examining bone composition and density are reported. Sr/sup 85/ was administered to seven osteoporotic patients as a tracer for skeletal mineral metabolism. The activity levels in the blood and the excretion rate were measured. From these data the accretion rate and the diffusible component volume were calculated. It was found that the accretion rate was not increased in any case. The size of the diffusible component was normal in six patients and reduced in one. Concurrent experimentsmore » with estrogen administration were conducted. Over-all results indicate that in osteoporosis, the rate of bone accretion is never elevated and an effect of estrogen administration was the decrease of bone resorption rather than stimulation of bone formation. In studies of skeletal metabolism, the kinetics of Sr/sup 85/ metabolism was compared in normal subjects and patients with skeletal disorders. Various aspects of the results are analyzed and it is concluded that values obtained by kinetic studies appear to be quantitative, reproducible, and to correlate with presently established information on alterations of bone metabolism in systemic deseases. In studies of peripheral circulation and bone growth, I/sup 131tagged human serum albumin was injected in animals. The investigation was conducted to determine blood volumne turnover rate in extremities, to correlate changes in this rate with fractures and bone disorders, and to examine the method for use in evaluation of circulation under certain pathological conditions. Data and findings are included. Data are also included on in vitro mobilization of Sr/ sup 85/ during bone formation and bone density studies. (J.R.D.)« less

Metabolic abnormalities in Williams-Beuren syndrome.

PubMed

Palacios-Verdú, María Gabriela; Segura-Puimedon, Maria; Borralleras, Cristina; Flores, Raquel; Del Campo, Miguel; Campuzano, Victoria; Pérez-Jurado, Luis Alberto

2015-04-01

Williams-Beuren syndrome (WBS, OMIM-194050) is a neurodevelopmental disorder with multisystemic manifestations caused by a 1.55-1.83 Mb deletion at 7q11.23 including 26-28 genes. Reported endocrine and metabolic abnormalities include transient hypercalcaemia of infancy, subclinical hypothyroidism in ∼ 30% of children and impaired glucose tolerance in ∼ 75% of adult individuals. The purpose of this study was to further study metabolic alterations in patients with WBS, as well as in several mouse models, to establish potential candidate genes. We analysed several metabolic parameters in a cohort of 154 individuals with WBS (data available from 69 to 151 cases per parameter), as well as in several mouse models with complete and partial deletions of the orthologous WBS locus, and searched for causative genes and potential modifiers. Triglyceride plasma levels were significantly decreased in individuals with WBS while cholesterol levels were slightly decreased compared with controls. Hyperbilirubinemia, mostly unconjugated, was found in 18.3% of WBS cases and correlated with subclinical hypothyroidism and hypotriglyceridemia, suggesting common pathogenic mechanisms. Haploinsufficiency at MLXIPL and increased penetrance for hypomorphic alleles at the UGT1A1 gene promoter might underlie the lipid and bilirubin alterations. Other disturbances included increased protein and iron levels, as well as the known subclinical hypothyroidism and glucose intolerance. Our results show that several unreported biochemical alterations, related to haploinsufficiency for specific genes at 7q11.23, are relatively common in WBS. The early diagnosis, follow-up and management of these metabolic disturbances could prevent long-term complications in this disorder. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Amino acid metabolic processes in the temporal lobes assessed by proton magnetic resonance spectroscopy (1H MRS) in children with Down syndrome.

PubMed

Śmigielska-Kuzia, Joanna; Boćkowski, Leszek; Sobaniec, Wojciech; Kułak, Wojciech; Sendrowski, Krzysztof

2010-01-01

Down syndrome (DS), or trisomy 21, is one of the most common autosomal mutations. The overexpression of the β-amyloid precursor protein gene, located on chromosome 21, causes an increased production of the specific amyloid. The current study is a continuation of our earlier investigations relating to the profile of metabolic changes in the frontal lobes of DS patients as assessed by proton magnetic resonance spectroscopy ((1)H MRS). The aims of the study were the morphological assessment of the brain using magnetic resonance imaging (MRI) and the evaluation of metabolic disorders of the temporal lobes using (1)H MRS in DS children. The study group included 20 children with DS aged 3-15 years and treated in the Department of Pediatric Neurology and Rehabilitation, Medical University of Białystok. The control group included healthy children (n = 20). MRI scans of the heads of DS children were performed using a 1.5 T MR scanner under standard conditions. (1)H MRS investigations were also carried out to assess metabolic changes in the temporal lobes. Metabolites, such as N-acetylaspartate (NAA), glutamate-glutamine complex (Glx), choline (Cho), myoinositol (mI) and γ-aminobutyric acid (GABA), were determined in both temporal lobes with reference to the internal marker creatine (Cr). Results were compared with the control group.We found a statistically significant decrease in NAA/Cr, Cho/Cr, mI/Cr and GABA/Cr ratios. The Glx/Cr ratio in both temporal lobes of DS patients did not differ from the control group. Our results indicate metabolic neurotransmitter disorders in the central nervous system in children with DS.

[Biochemical evaluation of metabolic disorders in the tissues of the locomotor system in patients with occupational diseases caused by physical stress].

PubMed

Shatskaia, N N; Tarasova, A A; Fedorova, V I; Shardakova, E F; Selezneva, A I; Fedosova, N F

1991-01-01

A group of patients with occupational disease and female sewing-machine operators were medically examined with a broad set of biochemical techniques aimed at the detection of metabolic disorders in the locomotor system tissues. Noninflammatory dystrophic changes were found. The muscular component was dominating in comparison with the osseous one in the genesis of the degenerative dystrophic processes, which manifested in the clinical course. Laboratory manifestations were revealed related to the lowered energy supply and oxygenation of the skeleton muscles in patients with neuromuscular and osteo-muscular++ syndromes. The metabolic disorders were diagnosed at the early stages of myalgia.

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives

PubMed Central

Lamonaca, Palma; Prinzi, Giulia; Kisialiou, Aliaksei; Cardaci, Vittorio; Fini, Massimo; Russo, Patrizia

2017-01-01

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI). PMID:28335527

[Clinical implications of polycystic ovary syndrome].

PubMed

Dravecká, Ingrid

Polycystic ovary syndrome (PCOS) is a heterogeneous and complex endocrine disease which among the female population belongs to the most widespread endocrinopathies and it is the most frequent cause of hyperthyroidism, anticoagulation and infertility. Insulin resistance is one of the important diabetology factors impacting hyperglycaemia in a majority of women with PCOS (60-80 %). Clinical expressions of PCOS include reproduction disorders, metabolic characteristics and psychological implications. Reproduction disorders include hyperthyroidism, menstruation cycle disorders, infertility and pregnancy complications as well as early abortions, gestational diabetes and pregnancy induced hypertension. Long-term metabolic risks of PCOS include type 2 diabetes mellitus, dyslipidemia, arterial hypertension and endothelial dysfunction. The available data confirms higher incidence of cardiovascular diseases in women with PCOS. In particular among obese women PCOS is more frequently associated with non-alcoholic hepatic steatosis, sleep apnoea syndrome and endometrial cancer. The literature includes some controversial data about the relationship between PCOS and autoimmunity. Women with PCOS are more prone to suffer from insufficient confidence with higher incidence of anxiety, depression, bipolar disorder and eating disorders. autoimmunity - diabetes mellitus - pregnancy - insulin resistance - metabolic syndrome - menstrual disorders - polycystic ovary syndrome.

Inflammatory pathways in children with insufficient or disordered sleep.

PubMed

Kim, Jinkwan; Hakim, Fahed; Kheirandish-Gozal, Leila; Gozal, David

2011-09-30

Sleep is not only an essential physiological function, but also serves important roles in promoting growth, maturation, and overall health of children and adolescents. There is increasing interest regarding the impact of sleep and its disorders on the regulation of inflammatory processes and end-organ morbidities, particularly in the context of metabolic and cardiovascular diseases (CVD) and their complications. Obstructive sleep apnea syndrome (OSAS) is an increasingly common health problem in children, and in the last decade, the emergence of increasing obesity rates has further led to remarkable increases in the prevalence of OSAS, along with more prominent neurocognitive, behavioral, cardiovascular and metabolic morbidities. Although the underlying mechanisms leading to OSAS-induced morbidities are likely multi-factorial, and remain to be fully elucidated, activation of inflammatory pathways by OSAS has emerged as an important pathophysiological component of the end-organ injury associated with this disorder. To this effect, it would appear that OSAS could be viewed as a chronic, low-grade inflammatory disorder. Furthermore, the concurrent presence of obesity and OSAS poses a theoretically increased risk of OSAS-related complications. In this review, we will critically review the current state of research regarding the impact of insufficient and disrupted sleep and OSAS on the immune processes and inflammatory pathways that underlie childhood OSAS as a distinctive systemic inflammatory condition in children, and will explore potential interactions between OSAS and obesity. Copyright © 2011 Elsevier B.V. All rights reserved.

Classification of Systemic and Localized Sweating Disorders.

PubMed

Ohshima, Yuichiro; Tamada, Yasuhiko

2016-01-01

Hyperhidrosis can be subdivided into generalized hyperhidrosis, with increased sweating over the entire body, and focal hyperhidrosis, in which the excessive sweating is restricted to specific parts of the body. Generalized hyperhidrosis may be either primary (idiopathic) or secondary. Secondary generalized hyperhidrosis may be caused by infections such as tuberculosis, hyperthyroidism, endocrine and metabolic disturbances such as pheochromocytoma, neurological disorders, or drugs. Focal hyperhidrosis may also be primary (idiopathic) or secondary. Frey's syndrome is one form of secondary focal hyperhidrosis that occurs during eating together with reddening of the area in front of the ear following parotid gland surgery or injury. Primary focal hyperhidrosis is particularly common on the palms and soles of the feet, in the axilla, and on the head. Anhidrosis may be either congenital/genetic or acquired. Some of the most typical forms of congenital/genetic anhidrosis include hypohidrotic ectodermal dysplasia, congenital insensitivity to pain and anhidrosis, and Fabry disease. Acquired anhidrosis is classified as secondary anhidrosis, which may be due to an underlying disorder such as a neurological disorder, an endocrine or metabolic disturbance, or the effect of drugs, or idiopathic anhidrosis for which the pathology, cause, and mechanism are unknown. Idiopathic anhidrosis is classified into acquired idiopathic generalized anhidrosis (AIGA), idiopathic segmental anhidrosis, and Ross syndrome. AIGA is divided into three categories according to differences in the site of disturbance: (1) sudomotor neuropathy, (2) idiopathic pure sudomotor failure, and (3) sweat gland failure. © 2016 S. Karger AG, Basel.

A new coding system for metabolic disorders demonstrates gaps in the international disease classifications ICD-10 and SNOMED-CT, which can be barriers to genotype-phenotype data sharing.

PubMed

Sollie, Annet; Sijmons, Rolf H; Lindhout, Dick; van der Ploeg, Ans T; Rubio Gozalbo, M Estela; Smit, G Peter A; Verheijen, Frans; Waterham, Hans R; van Weely, Sonja; Wijburg, Frits A; Wijburg, Rudolph; Visser, Gepke

2013-07-01

Data sharing is essential for a better understanding of genetic disorders. Good phenotype coding plays a key role in this process. Unfortunately, the two most widely used coding systems in medicine, ICD-10 and SNOMED-CT, lack information necessary for the detailed classification and annotation of rare and genetic disorders. This prevents the optimal registration of such patients in databases and thus data-sharing efforts. To improve care and to facilitate research for patients with metabolic disorders, we developed a new coding system for metabolic diseases with a dedicated group of clinical specialists. Next, we compared the resulting codes with those in ICD and SNOMED-CT. No matches were found in 76% of cases in ICD-10 and in 54% in SNOMED-CT. We conclude that there are sizable gaps in the SNOMED-CT and ICD coding systems for metabolic disorders. There may be similar gaps for other classes of rare and genetic disorders. We have demonstrated that expert groups can help in addressing such coding issues. Our coding system has been made available to the ICD and SNOMED-CT organizations as well as to the Orphanet and HPO organizations for further public application and updates will be published online (www.ddrmd.nl and www.cineas.org). © 2013 WILEY PERIODICALS, INC.

Natural History Study of Children With Metachromatic Leukodystrophy

ClinicalTrials.gov

2016-04-19

Lipid Metabolism Disorders; Metachromatic Leukodystrophy (MLD); Nervous System Diseases; Brain Diseases; Central Nervous System Diseases; Demyelinating Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Sphingolipidoses; Hereditary Central Nervous System Demyelinating Diseases; Metabolic Inborn Brain Diseases; Lysosomal Storage Diseases; Metabolic Diseases; Sulfatidosis

Effects of stevia on synaptic plasticity and NADPH oxidase level of CNS in conditions of metabolic disorders caused by fructose.

PubMed

Chavushyan, V A; Simonyan, K V; Simonyan, R M; Isoyan, A S; Simonyan, G M; Babakhanyan, M A; Hovhannisyian, L E; Nahapetyan, Kh H; Avetisyan, L G; Simonyan, M A

2017-12-19

Excess dietary fructose intake associated with metabolic syndrome and insulin resistance and increased risk of developing type 2 diabetes. Previous animal studies have reported that diabetic animals have significantly impaired behavioural and cognitive functions, pathological synaptic function and impaired expression of glutamate receptors. Correction of the antioxidant status of laboratory rodents largely prevents the development of fructose-induced plurimetabolic changes in the nervous system. We suggest a novel concept of efficiency of Stevia leaves for treatment of central diabetic neuropathy. By in vivo extracellular studies induced spike activity of hippocampal neurons during high frequency stimulation of entorhinal cortex, as well as neurons of basolateral amygdala to high-frequency stimulation of the hippocampus effects of Stevia rebaudiana Bertoni plant evaluated in synaptic activity in the brain of fructose-enriched diet rats. In the conditions of metabolic disorders caused by fructose, antioxidant activity of Stevia rebaudiana was assessed by measuring the NOX activity of the hippocampus, amygdala and spinal cord. In this study, the characteristic features of the metabolic effects of dietary fructose on synaptic plasticity in hippocampal neurons and basolateral amygdala and the state of the NADPH oxidase (NOX) oxidative system of these brain formations are revealed, as well as the prospects for development of multitarget and polyfunctional phytopreparations (with adaptogenic, antioxidant, antidiabetic, nootropic activity) from native raw material of Stevia rebaudiana. Stevia modulates degree of expressiveness of potentiation/depression (approaches but fails to achieve the norm) by shifting the percentage balance in favor of depressor type of responses during high-frequency stimulation, indicating its adaptogenic role in plasticity of neural networks. Under the action of fructose an increase (3-5 times) in specific quantity of total fraction of NOX isoforms isolated from the central nervous system tissue (amygdala, hippocampus, spinal cord) was revealed. Stevia exhibits an antistress, membrane-stabilizing role reducing the level of total fractions of NOX isoforms from central nervous system tissues and regulates NADPH-dependent O 2 - -producing activity. Generally, in condition of metabolic disorders caused by intensive consumption of dietary fructose Stevia leaves contributes to the control of neuronal synaptic plasticity possibly influencing the conjugated NOX-specific targets.

[Non-alcoholic fatty liver disease, as a component of the metabolic syndrome, and its causal correlations with other extrahepatic diseases].

PubMed

Halmos, Tamás; Suba, Ilona

2017-12-01

Non-alcoholic fatty liver disease is the most common non-infectious chronic liver-disease in our age, and is a spectrum of all the diseases associated with increased fat accumulation in the hepatocytes. Its development is promoted by sedentary life-style, over-feeding, and certain genetic predisposition. Prevalence in the adult population, even in Hungary is ~30%. In a part of cases, this disease may pass into non-alcoholic steatohepatitis, later into fibrosis, rarely into primary hepatocellular cancer. Fatty liver is closely and bidirectionally related to the metabolic syndrome and type 2 diabetes, and nowadays there is a general consensus that fatty liver is the hepatic manifestation of the metabolic sycndrome. The importance of the fatty liver has been highly emphasized recently. In addition to the progression into steatohepatitis, its causal relationship with numerous extrahepatic disorders has been discovered. In our overview, we deal with the epidemiology, pathomechanism of the disease, discuss the possibilities of diagnosis, its relationship with the intestinal microbiota, its recently recognized correlations with bile acids and their receptors, and its supposed correlations with the circadian CLOCK system. Hereinafter, we overview those extrahepatic disorders, which have been shown to be causal link with the non-alcoholic fatty liver disease. Among these, we emphasize the metabolic syndrome/type 2 diabetes, cardiovascular disorders, chronic kidney disease, sleep apnea/hypoventilation syndrome, inflammatory bowel disease, Alzheimer's disease, osteoporosis, and psoriasis, as well. Based on the above, it can be stated, that high risk individuals with non-alcoholic fatty liver disease need systemic care, and require the detection of other components of this systemic pathological condition. While currently specific therapy for the disease is not yet known, life-style changes, adequate use of available medicines can prevent disease progression. Promising research is under way, including drugs, manipulation of the intestinal flora or the possibility of therapeutic use of bile acid receptors, and also bariatric surgery. Orv Hetil. 2017; 158(52): 2051-2061.

Subclinical hypothyroidism in patients with non-alcoholic fatty liver disease at the background of carbohydrate metabolism disorders.

PubMed

Feisa, Snizhana V; Chopei, Ivan V

2018-01-01

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) is 25-30% in the general population and more than 75% among patients with carbohydrate metabolism disorders. One in six patients with NAFLD has concomitant subclinical hypothyroidism. The aim is to compare lipid and carbohydrate metabolism states in patients with NAFLD depending on the functional state of the thyroid gland. Materials and methods:215 patients with NAFLD and type 2 diabetes mellitus (T2-DM) or pre-diabetes (PD) were involved in study and devided into 6 groups according to the functional state of the thyroid gland. Results: In cases of adding subclinical hypothyroidism systolic and diastolic blood pressure are rising. In patients with overt hypothyroidism average HOMA-IR index is 29,98±1,05, which exceeds the corresponding figure in patients with concomitant subclinical hypothyroidism. In patients whose hypothyroidism has been compensated by levothyroxine, HOMA-IR index was reduced to 18,56±1,58, indicating a tendency to restore the sensitivity of peripheral tissues to insulin, on the assumption under the medicatedcorrection of thyroid functional status. Levels of common cholesterol and triglycerides were higher in cases of NAFLD with subclinical or overt hypothyroidism than in patients with NAFLD and normal thyroid function. Replacement therapy by levothyroxine leads to improving of lipid changes in patients with NAFLD and concomitant overt hypothyroidism: the levels of common cholesterol and triglycerides were reducing from 6,04±1,18 mmol/l and 3,96±1,34 mmol/l to 5,97±1,1 mmol/l and 3,45±1,13 mmol/l in accordance. Conclusions: Concomitant subclinical hypothyroidism in patients with NAFLD at the background of carbohydrate metabolism disorders leads to atherogenic dyslipidemia, increasing of blood atherogenicity. The index of lipid accumulated product (LAP) and the resistance of peripheral tissues to insulin also increases.

Phosphorylation of Threonine 175 Tau in the Induction of Tau Pathology in Amyotrophic Lateral Sclerosis-Frontotemporal Spectrum Disorder (ALS-FTSD). A Review.

PubMed

Moszczynski, Alexander J; Hintermayer, Matthew A; Strong, Michael J

2018-01-01

Approximately 50-60% of all patients with amyotrophic lateral sclerosis (ALS) will develop a deficit of frontotemporal function, ranging from frontotemporal dementia (FTD) to one or more deficits of neuropsychological, speech or language function which are collectively known as the frontotemporal spectrum disorders of ALS (ALS-FTSD). While the neuropathology underlying these disorders is most consistent with a widespread alteration in the metabolism of transactive response DNA-binding protein 43 (TDP-43), in both ALS with cognitive impairment (ALSci) and ALS with FTD (ALS-FTD; also known as MND-FTD) there is evidence for alterations in the metabolism of the microtubule associated protein tau. This alteration in tau metabolism is characterized by pathological phosphorylation at residue Thr 175 (pThr 175 tau) which in vitro is associated with activation of GSK3β (pTyr 216 GSK3β), phosphorylation of Thr 231 tau, and the formation of cytoplasmic inclusions with increased rates of cell death. This putative pathway of pThr 175 induction of pThr 231 and the formation of pathogenic tau inclusions has been recently shown to span a broad range of tauopathies, including chronic traumatic encephalopathy (CTE) and CTE in association with ALS (CTE-ALS). This pathway can be experimentally triggered through a moderate traumatic brain injury, suggesting that it is a primary neuropathological event and not secondary to a more widespread neuronal dysfunction. In this review, we discuss the neuropathological underpinnings of the postulate that ALS is associated with a tauopathy which manifests as a FTSD, and examine possible mechanisms by which phosphorylation at Thr 175 tau is induced. We hypothesize that this might lead to an unfolding of the hairpin structure of tau, activation of GSK3β and pathological tau fibril formation through the induction of cis -Thr 231 tau conformers. A potential role of TDP-43 acting synergistically with pathological tau metabolism is proposed.

Metabolic disorders causing childhood ataxia.

PubMed

Parker, Colette C; Evans, Owen B

2003-09-01

Ataxia is a common neurologic finding in many disease processes of the nervous system, and has classically been associated with numerous metabolic disorders. An error of metabolism should be considered when the ataxia is either intermittent or progressive. Acute exacerbation or worsening after high protein ingestion, concurrent febrile illness, or other physical stress is also suggestive. A positive family history can be an important diagnostic clue. Progressive molecular and biochemical techniques are revolutionizing this area of medicine, and there has been rapid advancement in understanding of the disease processes.

Newborn screening of metabolic disorders: recent progress and future developments.

PubMed

Rinaldo, Piero; Lim, James S; Tortorelli, Silvia; Gavrilov, Dimitar; Matern, Dietrich

2008-01-01

Tandem mass spectrometry has been the main driver behind a significant expansion in newborn screening programs. The ability to detect more than 40 conditions by a single test underscores the need to better understand the clinical and laboratory characteristics of the conditions being tested, and the complexity of pattern recognition and differential diagnoses of one or more elevated markers. The panel of conditions recommended by the American College of Medical Genetics, including 20 primary conditions and 22 secondary targets that are detectable by tandem mass spectrometry has been adopted as the standard of care in the vast majority of US states. The evolution of newborn screening is far from being idle as a large number of infectious, genetic, and metabolic conditions are currently under investigation at variable stages of test development and clinical validation. In the US, a formal process with oversight by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children has been established for nomination and evidence-based review of new candidate conditions. If approved, these conditions could be added to the uniform panel and consequently pave the way to large scale implementation.

Bisphenol A, Obesity, and Type 2 Diabetes Mellitus: Genuine Concern or Unnecessary Preoccupation?

PubMed Central

Mirmira, Priyadarshini; Evans-Molina, Carmella

2014-01-01

Bisphenol A or BPA is a ubiquitious industrial chemical found in a variety of plastic containers intended for food storage and in the epoxy resin linings of metal food and beverage cans, where it is used to prevent corrosion, food contamination, and spoilage. BPA has been recently linked to a wide variety of medical disorders and is known to have estrogenic activity with genomic as well as non-genomic estrogen-receptor mediated effects. Given rapidly increasing prevalence rates of metabolic disorders like obesity and Type 2 diabetes, BPA has recently come under intense scrutiny in scientific and lay communities as a potential endocrine disrupting compound with diabetogenic effects. The purpose of this review is to critically examine available literature investigating the link between BPA and alterations in metabolic health. Here, we discuss typical levels of exposure to BPA in daily life and analyze both epidemiological human data and mechanistic preclinical studies that have tested associations between BPA and obesity and diabetes. Finally, we summarize the current policies and views of national and international regulatory agencies regarding the safety of BPA use. PMID:24686036

X-linked hypophosphataemia: a homologous disorder in humans and mice.

PubMed

Tenenhouse, H S

1999-02-01

X-linked hypophosphatemia is an inherited disorder of phosphate (Pi) homeostasis characterized by growth retardation, rickets and osteomalacia, hypophosphataemia, and aberrant renal Pi reabsorption and vitamin D metabolism. Studies in murine Hyp and Gy homologues have identified a specific defect in Na+-Pi cotransport at the brush border membrane, abnormal regulation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) synthesis and degradation, and an intrinsic defect in bone mineralization. The mutant gene has been identified in XLH patients, by positional cloning, and in Hyp and Gy mice, and was designated PHEX/Phex to signify a PHosphate-regulating gene with homology to Endopeptidases on the X chromosome. PHEX/Phex is expressed in bones and teeth but not in kidney and efforts are under way to elucidate how loss of PHEX/Phex function elicits the mutant phenotype. Based on its homology to endopeptidases, it is postulated that PHEX/Phex is involved in the activation or inactivation of a peptide hormone(s) which plays a key role in the regulation of bone mineralization, renal Pi handling and vitamin D metabolism.

FoxO Transcription Factors and Regenerative Pathways in Diabetes Mellitus

PubMed Central

Maiese, Kenneth

2015-01-01

Mammalian forkhead transcription factors of the O class (FoxO) are exciting targets under consideration for the development of new clinical entities to treat metabolic disorders and diabetes mellitus (DM). DM, a disorder that currently affects greater than 350 million individuals globally, can become a devastating disease that leads to cellular injury through oxidative stress pathways and affects multiple systems of the body. FoxO proteins can regulate insulin signaling, gluconeogenesis, insulin resistance, immune cell migration, and cell senescence. FoxO proteins also control cell fate through oxidative stress and pathways of autophagy and apoptosis that either lead to tissue regeneration or cell demise. Furthermore, FoxO signaling can be dependent upon signal transduction pathways that include silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), Wnt, and Wnt1 inducible signaling pathway protein 1 (WISP1). Cellular metabolic pathways driven by FoxO proteins are complex, can lead to variable clinical outcomes, and require in-depth analysis of the epigenetic and post-translation protein modifications that drive FoxO protein activation and degradation. PMID:26256004

Approach to the genetics of alcoholism: a review based on pathophysiology.

PubMed

Köhnke, Michael D

2008-01-01

Alcohol dependence is a common disorder with a heterogenous etiology. The results of family, twin and adoption studies on alcoholism are reviewed. These studies have revealed a heritability of alcoholism of over 50%. After evaluating the results, it was epidemiologically stated that alcoholism is heterogenous complex disorder with a multiple genetic background. Modern molecular genetic techniques allow examining specific genes involved in the pathophysiology of complex diseases such as alcoholism. Strategies for gene identification are introduced to the reader, including family-based and association studies. The susceptibility genes that are in the focus of this article have been chosen because they are known to encode for underlying mechanisms that are linked to the pathophysiology of alcoholism or that are important for the pharmacotherapeutic approaches in the treatment of alcohol dependence. Postulated candidate genes of the metabolism of alcohol and of the involved neurotransmitter systems are introduced. Genetic studies on alcoholism examining the metabolism of alcohol and the dopaminergic, GABAergic, glutamatergic, opioid, cholinergic and serotonergic neurotransmitter systems as well as the neuropeptide Y are presented. The results are critically discussed followed by a discussion of possible consequences.

Interrelationship between Periapical Lesion and Systemic Metabolic Disorders

PubMed Central

Sasaki, Hajime; Hirai, Kimito; Martins, Christine Men; Furusho, Hisako; Battaglino, Ricardo; Hashimoto, Koshi

2016-01-01

Periapical periodontitis, also known as periapical lesion, is a common dental disease, along with periodontitis (gum disease). Periapical periodontitis is a chronic inflammatory disease, caused by endodontic infection, and its development is regulated by the host immune/inflammatory response. Metabolic disorders, which are largely dependent on life style such as eating habits, have been interpreted as a “metabolically-triggered” low-grade systemic inflammation and may interact with periapical periodontitis by triggering immune modulation. The host immune system is therefore considered the common fundamental mechanism of both disease conditions. An elevated inflammatory state caused by metabolic disorders can impact the clinical outcome of periapical lesions and interfere with wound healing after endodontic treatment. Although additional well-designed clinical studies are needed, periapical lesions appear to affect insulin sensitivity and exacerbate non-alcoholic steatohepatitis. Immune regulatory cytokines produced by various cell types, including immune cells and adipose tissue, play an important role in this interrelationship. PMID:26881444

Urea cycle disorder--argininosuccinic lyase deficiency.

PubMed

Mehta, Neeta; Kirk, Pia Chatterjee; Holder, Ray; Precheur, Harry V

2012-01-01

An increased level of ammonia in the bloodstream, or hyperammonemia, is a symptom associated with metabolic disorders referred to as inborn errors of metabolism. Urea cycle disorder is a congenital abnormality or absence of one of the six enzymes involved in the elimination of ammonia. Administration of certain medications, high protein diet, excessive exercise, surgical procedures, or trauma can precipitate symptoms of mental confusion, seizure-like activity, and ataxia. This paper reviews the literature with insight into current treatment and management options of the disorder and modification of treatment for the dental patient. © 2012 Special Care Dentistry Association and Wiley Periodicals, Inc.

Insights into the Roles of Gut Microbes in Obesity

PubMed Central

Sanz, Yolanda; Santacruz, Arlette; De Palma, Giada

2008-01-01

Obesity is a major public health issue as it enhances the risk of suffering several chronic diseases of increasing prevalence. Obesity results from an imbalance between energy intake and expenditure, associated with a chronic low-grade inflammation. Gut microbes are considered to contribute to body weight regulation and related disorders by influencing metabolic and immune host functions. The gut microbiota as a whole improves the host's ability to extract and store energy from the diet leading to body weight gain, while specific commensal microbes seem to exert beneficial effects on bile salt, lipoprotein, and cholesterol metabolism. The gut microbiota and some probiotics also regulate immune functions, protecting the host form infections and chronic inflammation. In contrast, dysbiosis and endotoxaemia may be inflammatory factors responsible for developing insulin resistance and body weight gain. In the light of the link between the gut microbiota, metabolism, and immunity, the use of dietary strategies to modulate microbiota composition is likely to be effective in controlling metabolic disorders. Although so far only a few preclinical and clinical trials have demonstrated the effects of specific gut microbes and prebiotics on biological markers of these disorders, the findings indicate that advances in this field could be of value in the struggle against obesity and its associated-metabolic disorders. PMID:19259329

Are oxidative stress markers useful to distinguish schizoaffective disorder from schizophrenia and bipolar disorder?

PubMed

Bulbul, Feridun; Virit, Osman; Alpak, Gokay; Unal, Ahmet; Bulut, Mahmut; Kaya, Mehmet Cemal; Altindag, Abdurrahman; Celik, Hakim; Savas, Haluk A

2014-04-01

Schizoaffective disorder is a disease with both affective and psychotic symptoms. In this study, we aimed to compare oxidative metabolism markers of schizoaffective disorder, bipolar disorder and schizophrenic patients. Furthermore, we also aimed to investigate whether schizoaffective disorder could be differentiated from schizophrenia and bipolar disorder in terms of oxidative metabolism. Total oxidant status (TOS) and total antioxidant status (TAS) were measured in the blood samples that were collected from schizoaffective patients (n = 30), bipolar disorder patients (n = 30) and schizophrenic patients (n = 30). Oxidative stress index (OSI) was calculated by dividing TOS by TAS. TOS and OSI were found to be higher in patients with schizoaffective disorder compared with those in schizophrenia and bipolar disorder patients. TAS was not significantly different between the groups. Schizoaffective disorder was found to be different from bipolar disorder and schizophrenia in terms of oxidative parameters. This result may indicate that schizoaffective disorder could differ from bipolar disorder and schizophrenia in terms of biochemical parameters. Increased TOS levels observed in schizoaffective disorder may suggest poor clinical course and may be an indicator of poor prognosis.

[Acute Dystonia due to Aripiprazole Use in Two Children with Autism Spectrum Disorder in the First Five Years of Life].

PubMed

Küçükköse, Mustafa; Kabukçu Başay, Bürge

2017-01-01

Autism spectrum disorders (ASD) are neuropsychiatric disorders characterized by impairment in social interactions, in verbal and non-verbal communication, and restricted and stereotyped patterns of interest and behavior within the first 3 years of life. Pharmacologic interventions may be needed for the treatment of temper tantrums, aggression, hyperactivity, and stereotypes in children with ASD. The approval of aripiprazole by the United States Food and Drug Administration (USFDA) for the treatment of temper tantrums in children and adolescents with ASD has gained increased interest for the use in these patients. Aripiprazole is a partial agonist for the dopamine D2, serotonin 5-HT1A receptors, and an antagonist for 5HT2A receptors. Because aripiprazole is a partial agonist, it has been is speculated that aripiprazole has a protective effect for extrapyramidal side effects, movement disorders, and metabolic problems. But the increased use in children and adolescents is associated with an increase in the number of case reports related with such problems. Nevertheless, our review of the literature uncovered limited data regarding the association between acute dystonia and aripiprazole use in ASD children under five years of age is. In this paper, we present two cases of autistic spectrum disorder children with ages under 5 years that developed acute dystonia taking aripiprazole.

Preventive and Protective Properties of Zingiber officinale (Ginger) in Diabetes Mellitus, Diabetic Complications, and Associated Lipid and Other Metabolic Disorders: A Brief Review

PubMed Central

Li, Yiming; Tran, Van H.; Duke, Colin C.; Roufogalis, Basil D.

2012-01-01

Zingiber officinale (ginger) has been used as herbal medicine to treat various ailments worldwide since antiquity. Recent evidence revealed the potential of ginger for treatment of diabetes mellitus. Data from in vitro, in vivo, and clinical trials has demonstrated the antihyperglycaemic effect of ginger. The mechanisms underlying these actions are associated with insulin release and action, and improved carbohydrate and lipid metabolism. The most active ingredients in ginger are the pungent principles, gingerols, and shogaol. Ginger has shown prominent protective effects on diabetic liver, kidney, eye, and neural system complications. The pharmacokinetics, bioavailability, and the safety issues of ginger are also discussed in this update. PMID:23243452

[Procedural analysis of acid-base balance disorder: case serials in 4 patents].

PubMed

Ma, Chunyuan; Wang, Guijie

2017-05-01

To establish the standardization process of acid-base balance analysis, analyze cases of acid-base balance disorder with the aid of acid-base balance coordinate graph. The acid-base balance theory were reviewed systematically on recent research progress, and the important concepts, definitions, formulas, parameters, regularity and inference in the analysis of acid-base balance were studied. The analysis of acid-base balance disordered processes and steps were figured. The application of acid-base balance coordinate graph in the cases was introduced. The method of "four parameters-four steps" analysis was put forward to analyze the acid-base balance disorders completely. "Four parameters" included pH, arterial partial pressure of carbon dioxide (PaCO 2 ), HCO 3 - and anion gap (AG). "Four steps" were outlined by following aspects: (1) according to the pH, PaCO 2 and HCO 3 - , the primary or main types of acid-base balance disorder was determined; (2) primary or main types of acid-base disorder were used to choose the appropriate compensation formula and to determine the presence of double mixed acid-base balance disorder; (3) the primary acid-base balance disorders were divided into two parts: respiratory acidosis or respiratory alkalosis, at the same time, the potential HCO 3 - should be calculated, the measured HCO 3 - should be replaced with potential HCO 3 - , to determine whether there were three mixed acid-base disorders; (4) based on the above analysis the data judged as the simple AG increased-metabolic acidosis was needed to be further analyzed. The ratio of ΔAG↑/ΔHCO 3 - ↓ was also needed to be calculated, to determine whether there was normal AG metabolic acidosis or metabolic alkalosis. In the clinical practice, PaCO 2 (as the abscissa) and HCO 3 - (as the ordinate) were used to establish a rectangular coordinate system, through origin (0, 0) and coordinate point (40, 24) could be a straight line, and all points on the straight line pH were equal to 7.40. The acid-base balance coordinate graph could be divided into seven areas by three straight lines [namely pH = 7.40 isoline, PaCO 2 = 40 mmHg (1 mmHg = 0.133 kPa) line and HCO 3 - = 24 mmol/L line]: main respiratory alkalosis area, main metabolic alkalosis area, respiratory + metabolic alkalosis area, main respiratory acidosis area, main metabolic acidosis area, respiratory + metabolic acidosis area and normal area. It was easier to determine the type of acid-base balance disorders by identifying the location of the (PaCO 2 , HCO 3 - ) or (PaCO 2 , potential HCO 3 - ) point on the acid-base balance coordinate graph. "Four parameters-four steps" method is systematic and comprehensive. At the same time, by using the acid-base balance coordinate graph, it is simpler to estimate the types of acid-base balance disorders. It is worthy of popularizing and generalizing.

Mineral metabolism, mortality, and morbidity in maintenance hemodialysis.

PubMed

Block, Geoffrey A; Klassen, Preston S; Lazarus, J Michael; Ofsthun, Norma; Lowrie, Edmund G; Chertow, Glenn M

2004-08-01

Mortality rates in ESRD are unacceptably high. Disorders of mineral metabolism (hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism) are potentially modifiable. For determining associations among disorders of mineral metabolism, mortality, and morbidity in hemodialysis patients, data on 40,538 hemodialysis patients with at least one determination of serum phosphorus and calcium during the last 3 mo of 1997 were analyzed. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum phosphorus, calcium, calcium x phosphorus product, and intact parathyroid hormone (PTH) using proportional hazards regression. Also determined was whether disorders of mineral metabolism were associated with all-cause, cardiovascular, infection-related, fracture-related, and vascular access-related hospitalization. After adjustment for case mix and laboratory variables, serum phosphorus concentrations >5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and >/=9.0 mg/dl). Higher adjusted serum calcium concentrations were also associated with an increased risk of death, even when examined within narrow ranges of serum phosphorus. Moderate to severe hyperparathyroidism (PTH concentrations >/=600 pg/ml) was associated with an increase in the relative risk of death, whereas more modest increases in PTH were not. When examined collectively, the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperphosphatemia. Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients.

Metabolic cutis laxa syndromes.

PubMed

Mohamed, Miski; Kouwenberg, Dorus; Gardeitchik, Thatjana; Kornak, Uwe; Wevers, Ron A; Morava, Eva

2011-08-01

Cutis laxa is a rare skin disorder characterized by wrinkled, redundant, inelastic and sagging skin due to defective synthesis of elastic fibers and other proteins of the extracellular matrix. Wrinkled, inelastic skin occurs in many cases as an acquired condition. Syndromic forms of cutis laxa, however, are caused by diverse genetic defects, mostly coding for structural extracellular matrix proteins. Surprisingly a number of metabolic disorders have been also found to be associated with inherited cutis laxa. Menkes disease was the first metabolic disease reported with old-looking, wrinkled skin. Cutis laxa has recently been found in patients with abnormal glycosylation. The discovery of the COG7 defect in patients with wrinkled, inelastic skin was the first genetic link with the Congenital Disorders of Glycosylation (CDG). Since then several inborn errors of metabolism with cutis laxa have been described with variable severity. These include P5CS, ATP6V0A2-CDG and PYCR1 defects. In spite of the evolving number of cutis laxa-related diseases a large part of the cases remain genetically unsolved. In metabolic cutis laxa syndromes the clinical and laboratory features might partially overlap, however there are some distinct, discriminative features. In this review on metabolic diseases causing cutis laxa we offer a practical approach for the differential diagnosis of metabolic cutis laxa syndromes.

Overcoming sleep disordered breathing and ensuring sufficient good sleep time for a healthy life expectancy

PubMed Central

CHIN, Kazuo

2017-01-01

Recent advances in basic and clinical medicine have resulted in major improvements in human health. Currently sleep has been considered an essential factor in maintaining and promoting a healthy life expectancy. Sleep disorders include more than 60 diseases. Sleep disordered breathings (SDB) have 17 disorders, including sleep apnea. SDB usually induces hypoxemia and hypercapnia, which would have significant effects on cells, organs, and the whole body. We have investigated SDB for nearly 35 years. We found that SDB has significant associations with humoral factors, including coagulation systems, the body’s protective factors against diseases, and metabolic and organ diseases. Currently we have been giving attention to the associations among SDB, short sleep duration, and obesity. In addition, SDB is important not only in the home but under critical care such as in the perioperative stage. In this review, I would like to describe several aspects of SDB in relation to systemic diseases and overall health based mainly on our published reports. PMID:29021511

Neuroimaging in psychiatric pharmacogenetics research: the promise and pitfalls.

PubMed

Falcone, Mary; Smith, Ryan M; Chenoweth, Meghan J; Bhattacharjee, Abesh Kumar; Kelsoe, John R; Tyndale, Rachel F; Lerman, Caryn

2013-11-01

The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype × drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment.

Metabolic Disorders in the Transition Period Indicate that the Dairy Cows’ Ability to Adapt is Overstressed

PubMed Central

Sundrum, Albert

2015-01-01

Simple Summary Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. Problems derive from difficulties animals have to adapt to large variations and disturbances occurring both outside and inside the organism. A lack of success in solving these issues may be due to predominant approaches in farm management and agricultural science, dealing with such disorders as merely negative side effects. Instead, a successful adaptation of animals to their living conditions should be seen as an important end in itself. Both farm management and agricultural sciences should support animals in their ability to cope with nutritional and metabolic challenges by employing a functional and result-driven approach. Abstract Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. They mainly derive from difficulties the animals have in adapting to changes and disturbances occurring both outside and inside the organisms and due to varying gaps between nutrient supply and demand. Adaptation is a functional and target-oriented process involving the whole organism and thus cannot be narrowed down to single factors. Most problems which challenge the organisms can be solved in a number of different ways. To understand the mechanisms of adaptation, the interconnectedness of variables and the nutrient flow within a metabolic network need to be considered. Metabolic disorders indicate an overstressed ability to balance input, partitioning and output variables. Dairy cows will more easily succeed in adapting and in avoiding dysfunctional processes in the transition period when the gap between nutrient and energy demands and their supply is restricted. Dairy farms vary widely in relation to the living conditions of the animals. The complexity of nutritional and metabolic processes and their large variations on various scales contradict any attempts to predict the outcome of animals’ adaptation in a farm specific situation. Any attempts to reduce the prevalence of metabolic disorders and associated production diseases should rely on continuous and comprehensive monitoring with appropriate indicators on the farm level. Furthermore, low levels of disorders and diseases should be seen as a further significant goal which carries weight in addition to productivity goals. In the long run, low disease levels can only be expected when farmers realize that they can gain a competitive advantage over competitors with higher levels of disease. PMID:26479480

[Alcoholic ketoacidosis and reversible neurological complications due to hypophosphataemia].

PubMed

Fernández López, Ma T; García Bargo, Ma D; Rivero Luis, Ma T; Álvarez Vázquez, P; Saenz Fernández, C A; Mato Mato, J A

2012-01-01

A 57-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and polyradiculitis. Laboratory examination revealed metabolic acidosis, hypokalemia and hypophosphataemia. Alcoholic ketoacidosis is a common disorder in alcoholic patients. All patients present with a history of heavy alcohol misuse, preceding a bout of particularly excesive intake, which had been terminated by nausea, vomiting and abdominal pain. The most important laboratory results are: normal or low glucose level, metabolic acidosis with a raised anion GAP, low or absent blood alcohol level and urinary ketones. The greatest threats to patients are: hypovolemia, hypokaliemia, hypoglucemia and acidosis. Alcohol abuse may result in a wide range of electrolyte and acid-base disorders including hypophosphataemia, hypomagnesemia, hypocalcemia, hypokalemia, metabolic acidosis and respiratory alkalosis. Disturbance of consciousness in alcoholic patients is observed in several disorders, such drunkenness, Wernicke encephalopathy, alcohol withdrawal syndrome, central pontine myelinolysis, hepatic encephalopathy, hypoglucemia and electrolyte disorders.

Aripiprazole for the maintenance treatment of bipolar I disorder: A review.

PubMed

McIntyre, Roger S

2010-01-01

Bipolar disorder is a chronic neuropsychiatric syndrome associated with substantial rates of recurrence, interepisodic dysfunction, comorbidity, and premature mortality. Metabolic comorbidity (eg, overweight, obesity, metabolic syndrome) differentially affects individuals with bipolar disorder and contributes to increased illness-associated morbidity and mortality (ie, cardiovascular disease). Few pharmacologic agents have been approved by the US Food and Drug Administration for the maintenance treatment of bipolar disorder. This paper discusses the metabolic profile of aripiprazole and reviews pivotal registration trials of aripiprazole for the maintenance treatment of adults with bipolar I disorder. MEDLINE was searched for English-language articles published between January 1995 and November 2009. The key search term was aripiprazole, combined with bipolar disorder and maintenance treatment. The review was limited to randomized, controlled registration trials, supplemented by poster presentations involving the registration-trial data sets. Three studies of the efficacy and tolerability of aripiprazole monotherapy in the maintenance treatment of bipolar I disorder were identified by the literature search: a 26-week, randomized, double-blind study and its 74-week extension phase (for a total of 100 weeks of double-blind treatment), and a randomized, double-blind comparison of aripiprazole with placebo and lithium (internal comparator) for up to 12 weeks. After 100 weeks of double-blind treatment, aripiprazole had a minimal effect on body composition and did not disrupt metabolic parameters compared with placebo. The mean (SD) weight change was 0.4 (0.8) kg with aripiprazole and -1.9 (0.8) kg with placebo (P = NS). A clinically significant (> or =7%) increase in weight occurred in 20% of the aripiprazole group and 5% of the placebo group (P = 0.01). Extrapyramidal symptoms were reported in 22% of the aripiprazole group and 15% of the placebo group. The identified trials of aripiprazole primarily enrolled patients during a manic state; no maintenance trials of combination therapy or trials enrolling individuals presenting with an acute depressive episode were identified. The available evidence supports the efficacy and tolerability of aripiprazole in the maintenance treatment of bipolar disorder. The placebo-subtracted differences in body composition and metabolic parameters suggest utility for aripiprazole in the long-term treatment of bipolar disorder. 2010 Excerpta Medica Inc. All rights reserved.

Metabolic screening and metabolomics analysis in the Intellectual Developmental Disorders Mexico Study.

PubMed

Ibarra-González, Isabel; Rodríguez-Valentín, Rocío; Lazcano-Ponce, Eduardo; Vela-Amieva, Marcela

2017-01-01

Inborn errors of metabolism (IEM) are genetic conditions that are sometimes associated with intellectual developmental disorders (IDD). The aim of this study is to contribute to the metabolic characterization of IDD of unknown etiology in Mexico. Metabolic screening using tandem mass spectrometry and fluorometry will be performed to rule out IEM. In addition, target metabolomic analysis will be done to characterize the metabolomic profile of patients with IDD. Identification of new metabolomic profiles associated with IDD of unknown etiology and comorbidities will contribute to the development of novel diagnostic and therapeutic schemes for the prevention and treatment of IDD in Mexico.

Association Between Vitamin D Insufficiency and Metabolic Syndrome in Patients With Psychotic Disorders.

PubMed

Yoo, Taeyoung; Choi, Wonsuk; Hong, Jin-Hee; Lee, Ju-Yeon; Kim, Jae-Min; Shin, Il-Seon; Yang, Soo Jin; Amminger, Paul; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

2018-04-01

This study examined the association between vitamin D and metabolic syndrome in patients with psychotic disorders. The study enrolled 302 community-dwelling patients with psychotic disorders. Sociodemographic and clinical characteristics, including blood pressure, physical activity, and dietary habit were gathered. Laboratory examinations included vitamin D, lipid profile, fasting plasma glucose, HbA1c, liver function, and renal function. Vitamin D insufficiency was defined as <20 ng/mL. Clinical characteristics associated with vitamin D insufficiency were identified. Among the 302 participants, 236 patients (78.1%) had a vitamin D insufficiency and 97 (32.1%) had metabolic syndrome. Vitamin D insufficiency was significantly associated with the presence of metabolic syndrome (p=0.006) and hypertension (p=0.017). Significant increases in triglycerides and alanine transaminase were observed in the group with a vitamin D insufficiency (p=0.002 and 0.011, respectively). After adjusting for physical activity and dietary habit scores, vitamin D insufficiency remained significantly associated with metabolic syndrome and hypertension. Vitamin D insufficiency was associated with metabolic syndrome and was particularly associated with high blood pressure, although the nature, direction and implications of this association are unclear.

Association Between Vitamin D Insufficiency and Metabolic Syndrome in Patients With Psychotic Disorders

PubMed Central

Yoo, Taeyoung; Choi, Wonsuk; Hong, Jin-Hee; Lee, Ju-Yeon; Kim, Jae-Min; Shin, Il-Seon; Yang, Soo Jin; Amminger, Paul; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

2018-01-01

Objective This study examined the association between vitamin D and metabolic syndrome in patients with psychotic disorders. Methods The study enrolled 302 community-dwelling patients with psychotic disorders. Sociodemographic and clinical characteristics, including blood pressure, physical activity, and dietary habit were gathered. Laboratory examinations included vitamin D, lipid profile, fasting plasma glucose, HbA1c, liver function, and renal function. Vitamin D insufficiency was defined as <20 ng/mL. Clinical characteristics associated with vitamin D insufficiency were identified. Results Among the 302 participants, 236 patients (78.1%) had a vitamin D insufficiency and 97 (32.1%) had metabolic syndrome. Vitamin D insufficiency was significantly associated with the presence of metabolic syndrome (p=0.006) and hypertension (p=0.017). Significant increases in triglycerides and alanine transaminase were observed in the group with a vitamin D insufficiency (p=0.002 and 0.011, respectively). After adjusting for physical activity and dietary habit scores, vitamin D insufficiency remained significantly associated with metabolic syndrome and hypertension. Conclusion Vitamin D insufficiency was associated with metabolic syndrome and was particularly associated with high blood pressure, although the nature, direction and implications of this association are unclear. PMID:29486549

Parma consensus statement on metabolic disruptors.

PubMed

Heindel, Jerrold J; Vom Saal, Frederick S; Blumberg, Bruce; Bovolin, Patrizia; Calamandrei, Gemma; Ceresini, Graziano; Cohn, Barbara A; Fabbri, Elena; Gioiosa, Laura; Kassotis, Christopher; Legler, Juliette; La Merrill, Michele; Rizzir, Laura; Machtinger, Ronit; Mantovani, Alberto; Mendez, Michelle A; Montanini, Luisa; Molteni, Laura; Nagel, Susan C; Parmigiani, Stefano; Panzica, Giancarlo; Paterlini, Silvia; Pomatto, Valentina; Ruzzin, Jérôme; Sartor, Giorgio; Schug, Thaddeus T; Street, Maria E; Suvorov, Alexander; Volpi, Riccardo; Zoeller, R Thomas; Palanza, Paola

2015-06-20

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.

[Diabetes and prediabetes in endocrine disorders].

PubMed

Krysiak, Robert; Rudzki, Henryk; Okopień, Bogusław

2012-01-01

Complex hormonal regulation of carbohydrate metabolism causes that presence of many endocrine disorders may disturb glucose homeostasis. Impaired fasting glucose, impaired glucose tolerance and frank diabetes are observed in patients with both common and rare endocrine disorders, particularly in patients with polycystic ovary syndrome, hyperthyroidism, Cushing's syndrome, pheochromocytoma, primary aldosteronism, acromegaly, growth hormone deficiency and endocrine tumors of the digestive system. Because most of these disorders may be effectively treated and the treatment often results in a restoration of normal insulin secretion and receptor action as well as glucose absorption, production and metabolism, it is important to differentiate these disorders from other more common types of diabetes. This article reviews the etiology, clinical manifestation, diagnosis and management of endocrine disorders leading to diabetes and prediabetic states with special emphasis on the pathogenesis and clinical consequences of these disorders.

The prelude on novel receptor and ligand targets involved in the treatment of diabetes mellitus.

PubMed

Jonnalagadda, Venu Gopal; Ram Raju, Allam Venkata Sita; Pittala, Srinivas; Shaik, Afsar; Selkar, Nilakash Annaji

2014-01-01

Metabolic disorders are a group of disorders, due to the disruption of the normal metabolic process at a cellular level. Diabetes Mellitus and Tyrosinaemia are the majorly reported metabolic disorders. Among them, Diabetes Mellitus is a one of the leading metabolic syndrome, affecting 5 to 7 % of the population worldwide and mainly characterised by elevated levels of glucose and is associated with two types of physiological event disturbances such as impaired insulin secretion and insulin resistance. Up to now, various treatment strategies are like insulin, alphaglucosidase inhibitors, biguanides, incretins were being followed. Concurrently, various novel therapeutic strategies are required to advance the therapy of Diabetes mellitus. For the last few decades, there has been an extensive research in understanding the metabolic pathways involved in Diabetes Mellitus at the cellular level and having the profound knowledge on cell-growth, cell-cycle, and apoptosis at a molecular level provides new targets for the treatment of Diabetes Mellitus. Receptor signalling has been involved in these mechanisms, to translate the information coming from outside. To understand the various receptors involved in these pathways, we must have a sound knowledge on receptors and ligands involved in it. This review mainly summarises the receptors and ligands which are involved the Diabetes Mellitus. Finally, researchers have to develop the alternative chemical moieties that retain their affinity to receptors and efficacy. Diabetes Mellitus being a metabolic disorder due to the glucose surfeit, demands the need for regular exercise along with dietary changes.

Diet and cognition: interplay between cell metabolism and neuronal plasticity

PubMed Central

Gomez-Pinilla, Fernando; Tyagi, Ethika

2014-01-01

Purpose of Study To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders. Recent Findings Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long term neuronal plasticity. Summary The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid DHA, disrupting neuronal signaling. Thus, dietary DHA seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor (BDNF) in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation. PMID:24071781

The role of genetic variation of human metabolism for BMI, mental traits and mental disorders.

PubMed

Hebebrand, Johannes; Peters, Triinu; Schijven, Dick; Hebebrand, Moritz; Grasemann, Corinna; Winkler, Thomas W; Heid, Iris M; Antel, Jochen; Föcker, Manuel; Tegeler, Lisa; Brauner, Lena; Adan, Roger A H; Luykx, Jurjen J; Correll, Christoph U; König, Inke R; Hinney, Anke; Libuda, Lars

2018-06-01

The aim was to assess whether loci associated with metabolic traits also have a significant role in BMI and mental traits/disorders METHODS: We first assessed the number of single nucleotide polymorphisms (SNPs) with genome-wide significance for human metabolism (NHGRI-EBI Catalog). These 516 SNPs (216 independent loci) were looked-up in genome-wide association studies for association with body mass index (BMI) and the mental traits/disorders educational attainment, neuroticism, schizophrenia, well-being, anxiety, depressive symptoms, major depressive disorder, autism-spectrum disorder, attention-deficit/hyperactivity disorder, Alzheimer's disease, bipolar disorder, aggressive behavior, and internalizing problems. A strict significance threshold of p < 6.92 × 10 -6 was based on the correction for 516 SNPs and all 14 phenotypes, a second less conservative threshold (p < 9.69 × 10 -5 ) on the correction for the 516 SNPs only. 19 SNPs located in nine independent loci revealed p-values < 6.92 × 10 -6 ; the less strict criterion was met by 41 SNPs in 24 independent loci. BMI and schizophrenia showed the most pronounced genetic overlap with human metabolism with three loci each meeting the strict significance threshold. Overall, genetic variation associated with estimated glomerular filtration rate showed up frequently; single metabolite SNPs were associated with more than one phenotype. Replications in independent samples were obtained for BMI and educational attainment. Approximately 5-10% of the regions involved in the regulation of blood/urine metabolite levels seem to also play a role in BMI and mental traits/disorders and related phenotypes. If validated in metabolomic studies of the respective phenotypes, the associated blood/urine metabolites may enable novel preventive and therapeutic strategies. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Unveiling the Metabolic Changes on Muscle Cell Metabolism Underlying p-Phenylenediamine Toxicity

PubMed Central

Marín de Mas, Igor; Marín, Silvia; Pachón, Gisela; Rodríguez-Prados, Juan C.; Vizán, Pedro; Centelles, Josep J.; Tauler, Romà; Azqueta, Amaya; Selivanov, Vitaly; López de Ceraín, Adela; Cascante, Marta

2017-01-01

Rhabdomyolysis is a disorder characterized by acute damage of the sarcolemma of the skeletal muscle leading to release of potentially toxic muscle cell components into the circulation, most notably creatine phosphokinase (CK) and myoglobulin, and is frequently accompanied by myoglobinuria. In the present work, we evaluated the toxicity of p-phenylenediamine (PPD), a main component of hair dyes which is reported to induce rhabdomyolysis. We studied the metabolic effect of this compound in vivo with Wistar rats and in vitro with C2C12 muscle cells. To this aim we have combined multi-omic experimental measurements with computational approaches using model-driven methods. The integrative study presented here has unveiled the metabolic disorders associated to PPD exposure that may underlay the aberrant metabolism observed in rhabdomyolys disease. Animals treated with lower doses of PPD (10 and 20 mg/kg) showed depressed activity and myoglobinuria after 10 h of treatment. We measured the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) in rats after 24, 48, and 72 h of PPD exposure. At all times, treatment with PPD at higher doses (40 and 60 mg/kg) showed an increase of AST and ALT, and also an increase of lactate dehydrogenase (LDH) and CK after 24 h. Blood packed cell volume and hemoglobin levels, as well as organs weight at 48 and 72 h, were also measured. No significant differences were observed in these parameters under any condition. PPD induce cell cycle arrest in S phase and apoptosis (40% or early apoptotic cells) on mus musculus mouse C2C12 cells after 24 h of treatment. Incubation of mus musculus mouse C2C12 cells with [1,2-13C2]-glucose during 24 h, subsequent quantification of 13C isotopologues distribution in key metabolites of glucose metabolic network and a computational fluxomic analysis using in-house developed software (Isodyn) showed that PPD is inhibiting glycolysis, non-oxidative pentose phosphate pathway, glycogen turnover, and ATPAse reaction leading to a reduction in ATP synthesis. These findings unveil the glucose metabolism collapse, which is consistent with a decrease in cell viability observed in PPD-treated C2C12 cells and with the myoglubinuria and other effects observed in Wistar Rats treated with PPD. These findings shed new light on muscle dysfunction associated to PPD exposure, opening new avenues for cost-effective therapies in Rhabdomyolysis disease. PMID:28321398

Short- and long-term health consequences of sleep disruption.

PubMed

Medic, Goran; Wille, Micheline; Hemels, Michiel Eh

2017-01-01

Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care professionals should be cognizant of how managing underlying medical conditions may help to optimize sleep continuity and consider prescribing interventions that minimize sleep disruption.

Short- and long-term health consequences of sleep disruption

PubMed Central

Medic, Goran; Wille, Micheline; Hemels, Michiel EH

2017-01-01

Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic–pituitary–adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care professionals should be cognizant of how managing underlying medical conditions may help to optimize sleep continuity and consider prescribing interventions that minimize sleep disruption. PMID:28579842

Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

NASA Astrophysics Data System (ADS)

Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

2016-08-01

Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.

Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

PubMed Central

Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

2016-01-01

Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns. PMID:27502578

Visual and Verbal Learning in a Genetic Metabolic Disorder

ERIC Educational Resources Information Center

Spilkin, Amy M.; Ballantyne, Angela O.; Trauner, Doris A.

2009-01-01

Visual and verbal learning in a genetic metabolic disorder (cystinosis) were examined in the following three studies. The goal of Study I was to provide a normative database and establish the reliability and validity of a new test of visual learning and memory (Visual Learning and Memory Test; VLMT) that was modeled after a widely used test of…

[Live style and risk of lifestyle diseases].

PubMed

Kábrt, Jan

2014-01-01

Metabolic syndrome included obesity, diabetes mellitus type II, hypertension and disorder of lipid metabolism are serious complication affecting many people of economic advanced countries. Unhealthy live style with limited physical activity and overfeeding are the main cause of this disorder. Adjustment of the live style with regular physical activity has the better result compared with a diet intervention alone.

Metabolic Syndrome in Children with and without Developmental Coordination Disorder

ERIC Educational Resources Information Center

Wahi, Gita; LeBlanc, Paul J.; Hay, John A.; Faught, Brent E.; O'Leary, Debra; Cairney, John

2011-01-01

Children with developmental coordination disorder (DCD) have higher rates of obesity compared to children with typical motor development, and, as a result may be at increased risk for developing metabolic syndrome (MetS). The purpose of this study was to determine the presence of MetS and its components among children with and without DCD. This…

Metabolic Profiling of Liver Tissue in Diabetic Mice Treated with Artemisia Capillaris and Alisma Rhizome Using LC-MS and CE-MS.

PubMed

Kim, Yumi; Lee, In-Seung; Kim, Kang-Hoon; Park, Jiyoung; Lee, Ji-Hyun; Bang, Eunjung; Jang, Hyeung-Jin; Na, Yun-Cheol

2016-01-01

Artemisia Capillaris (AC) and Alisma Rhizome (AR) are natural products for the treatment of liver disorders in oriental medicine clinics. Here, we report metabolomic changes in the evaluation of the treatment effects of AC and AR on fatty livers in diabetic mice, along with a proposition of the underlying metabolic pathway. Hydrophobic and hydrophilic metabolites extracted from mouse livers were analyzed using HPLC-QTOF and CE-QTOF, respectively, to generate metabolic profiles. Statistical analysis of the metabolites by PLS-DA and OPLA-DA fairly discriminated between the diabetic, and the AC- and AR-treated mice groups. Various PEs mostly contributed to the discrimination of the diabetic mice from the normal mice, and besides, DG (18:1/16:0), TG (16:1/16:1/20:1), PE (21:0/20:5), and PA (18:0/21:0) were also associated with discrimination by s-plot. Nevertheless, the effects of AC and AR treatment were indistinct with respect to lipid metabolites. Of the 97 polar metabolites extracted from the CE-MS data, 40 compounds related to amino acid, central carbon, lipid, purine, and pyrimidine metabolism, with [Formula: see text] values less than 0.05, were shown to contribute to liver dysregulation. Following treatment with AC and AR, the metabolites belonging to purine metabolism preferentially recovered to the metabolic state of the normal mice. The AMP/ATP ratio of cellular energy homeostasis in AR-treated mice was more apparently increased ([Formula: see text]) than that of AC-treated mice. On the other hand, amino acids, which showed the main alterations in diabetic mice, did not return to the normal levels upon treatment with AR or AC. In terms of metabolomics, AR was a more effective natural product in the treatment of liver dysfunction than AC. These results may provide putative biomarkers for the prognosis of fatty liver disorder following treatment with AC and AR extracts.

In vivo and in silico dynamics of the development of Metabolic Syndrome.

PubMed

Rozendaal, Yvonne J W; Wang, Yanan; Paalvast, Yared; Tambyrajah, Lauren L; Li, Zhuang; Willems van Dijk, Ko; Rensen, Patrick C N; Kuivenhoven, Jan A; Groen, Albert K; Hilbers, Peter A J; van Riel, Natal A W

2018-06-01

The Metabolic Syndrome (MetS) is a complex, multifactorial disorder that develops slowly over time presenting itself with large differences among MetS patients. We applied a systems biology approach to describe and predict the onset and progressive development of MetS, in a study that combined in vivo and in silico models. A new data-driven, physiological model (MINGLeD: Model INtegrating Glucose and Lipid Dynamics) was developed, describing glucose, lipid and cholesterol metabolism. Since classic kinetic models cannot describe slowly progressing disorders, a simulation method (ADAPT) was used to describe longitudinal dynamics and to predict metabolic concentrations and fluxes. This approach yielded a novel model that can describe long-term MetS development and progression. This model was integrated with longitudinal in vivo data that was obtained from male APOE*3-Leiden.CETP mice fed a high-fat, high-cholesterol diet for three months and that developed MetS as reflected by classical symptoms including obesity and glucose intolerance. Two distinct subgroups were identified: those who developed dyslipidemia, and those who did not. The combination of MINGLeD with ADAPT could correctly predict both phenotypes, without making any prior assumptions about changes in kinetic rates or metabolic regulation. Modeling and flux trajectory analysis revealed that differences in liver fluxes and dietary cholesterol absorption could explain this occurrence of the two different phenotypes. In individual mice with dyslipidemia dietary cholesterol absorption and hepatic turnover of metabolites, including lipid fluxes, were higher compared to those without dyslipidemia. Predicted differences were also observed in gene expression data, and consistent with the emergence of insulin resistance and hepatic steatosis, two well-known MetS co-morbidities. Whereas MINGLeD specifically models the metabolic derangements underlying MetS, the simulation method ADAPT is generic and can be applied to other diseases where dynamic modeling and longitudinal data are available.

Metabolic mapping of the effects of the antidepressant fluoxetine on the brains of congenitally helpless rats.

PubMed

Shumake, Jason; Colorado, Rene A; Barrett, Douglas W; Gonzalez-Lima, F

2010-07-09

Antidepressants require adaptive brain changes before efficacy is achieved, and they may impact the affectively disordered brain differently than the normal brain. We previously demonstrated metabolic disturbances in limbic and cortical regions of the congenitally helpless rat, a model of susceptibility to affective disorder, and we wished to test whether administration of fluoxetine would normalize these metabolic differences. Fluoxetine was chosen because it has become a first-line drug for the treatment of affective disorders. We hypothesized that fluoxetine antidepressant effects may be mediated by decreasing metabolism in the habenula and increasing metabolism in the ventral tegmental area. We measured the effects of fluoxetine on forced swim behavior and regional brain cytochrome oxidase activity in congenitally helpless rats treated for 2 weeks with fluoxetine (5mg/kg, i.p., daily). Fluoxetine reduced immobility in the forced swim test as anticipated, but congenitally helpless rats responded in an atypical manner, i.e., increasing climbing without affecting swimming. As hypothesized, fluoxetine reduced metabolism in the habenula and increased metabolism in the ventral tegmental area. In addition, fluoxetine reduced the metabolism of the hippocampal dentate gyrus and dorsomedial prefrontal cortex. This study provided the first detailed mapping of the regional brain effects of an antidepressant drug in congenitally helpless rats. All of the effects were consistent with previous studies that have metabolically mapped the effects of serotonergic antidepressants in the normal rat brain, and were in the predicted direction of metabolic normalization of the congenitally helpless rat for all affected brain regions except the prefrontal cortex. Copyright (c) 2010 Elsevier B.V. All rights reserved.

[Metabolic safety of antidepressant medicines].

PubMed

Łężak, Wojciech; Mokros, Łukasz; Karbownik, Michał Seweryn; Witusik, Andrzej; Kosmalski, Marcin; Kowalczyk, Edward; Pietras, Tadeusz

2017-05-23

Metabolic syndrome is a very serious health issue, not only from internal medicine's point of view. Patients suffering from overweight, arterial hypertension, lipids and carbohydrates metabolism disorders are also in the circle of interest of other areas of medicine, including psychiatry. Currently, one of key problems of pharmacotherapy is a comorbidity of metabolic syndrome and mental disorder. Depression is more common than schizophrenia. Despite the fact that in everyday clinical practice there are more patients with depression than schizophrenia, there is a bigger interest among scientists for metabolic syndrome after antipsychotic drugs than as an effect of use of antidepressant agents. The aim of an analysis was to review literature committed to influence of depression pharmacotherapy on development of metabolic syndrome. 169 results were provided, including 18 original publications. Final analysis consists of 9 that investigate correlation between antidepressive medicines use and metabolic syndrome development (but not its each individual component). In general, antidepressant pharmacotherapy is associated not only with increased risk of metabolic syndrome occurrence but also their worsening. However, it needs to be emphasized that there is a difference between antidepressants groups - tricyclic antidepressive medicines are the most commonly associated with risk of developing metabolic disorders, but also SNRIs and SSRIs are mentioned as significant contributors. Mechanisms of aforementioned changes are still unclear. However, their influence on histamine and serotonin pathways, which take part in regulation of i.e. food intake, is suggested. The search for mechanisms that are precisely responsible for metabolic changes continues, in hope of finding a way to avoid adverse effects of antidepressant medicines use.

Incidence, nature, and etiology of metabolic alkalosis in dogs and cats.

PubMed

Ha, Y-S; Hopper, K; Epstein, S E

2013-01-01

The incidence and causes of metabolic alkalosis in dogs and cats have not been fully investigated. To describe the incidence, nature, and etiology of metabolic alkalosis in dogs and cats undergoing blood gas analysis at a veterinary teaching hospital. Dogs and cats at a veterinary medical teaching hospital. Acid-base and electrolyte results for dogs and cats measured during a 13-month period were retrospectively collected from a computer database. Only the first measured (venous or arterial) blood gas analyzed in a single hospitalization period was included. Animals with a base excess above the reference range for the species were included. A total of 1,805 dogs and cats were included. Of these, 349 (19%) were identified as having an increased standardized base excess, 319 dogs and 30 cats. The mixed acid-base disorder of metabolic alkalosis with respiratory acidosis was the most common abnormality identified in both dogs and cats. Hypokalemia and hypochloremia were more common in animals with metabolic alkalosis compared to animals without metabolic alkalosis. The 4 most commonly identified underlying diseases were respiratory disease, gastrointestinal tract obstruction, furosemide administration, and renal disease. Metabolic alkalosis was less common than metabolic acidosis in the same population of animals. Evidence of contraction alkalosis was present in many patients in this study. Hypokalemia and hypochloremia were more frequent in patients with metabolic alkalosis and suggest the importance of evaluation of acid-base status in conjunction with serum electrolyte concentrations. Copyright © 2013 by the American College of Veterinary Internal Medicine.

The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression.

PubMed

Liu, Lanxiang; Zhou, Xinyu; Zhang, Yuqing; Liu, Yiyun; Yang, Lining; Pu, Juncai; Zhu, Dan; Zhou, Chanjuan; Xie, Peng

2016-05-15

Major depressive disorder, with serious impairment in cognitive and social functioning, is a complex psychiatric disorder characterized by pervasive and persistent low mood and a loss of interest or pleasure. However, the underlying molecular mechanisms of depression remain largely unknown. In this study, we used a non-targeted metabolomics approach based on gas chromatography-mass spectrometry of the prefrontal cortex in chronic restraint stress (CRS)-treated rats. CRS was induced in the stress group by restraining rats in a plastic restrainer for 6h every day. This stress paradigm continued for 21 days. Body weight measurement and behavior tests were applied, including the sucrose preference test for anhedonia, the forced swimming test for despair-like behavior, and open field test and the elevated plus-maze to test for anxiety-like behaviors in rats after CRS. Differentially expressed metabolites associated with CRS-treated rats were identified by combining multivariate and univariate statistical analysis and corrected for multiple testing using the Benjamini-Hochberg procedure. A heat map of differential metabolites was constructed using Matlab. Ingenuity Pathways Analysis was applied to identify the predicted pathways and biological functions relevant to the bio-molecules of interest. Our findings showed that CRS induces depression-like behaviors and not anxiety-like behaviors. Thirty-six metabolites were identified as potential depression biomarkers involved in amino acid metabolism, energy metabolism and lipid metabolism, as well as a disturbance in neurotransmitters. Consequently, this study provides useful insights into the molecular mechanisms of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Adipocyte Glucocorticoid Receptor Deficiency Attenuates Aging- and HFD-Induced Obesity and Impairs the Feeding-Fasting Transition.

PubMed

Mueller, Kristina M; Hartmann, Kerstin; Kaltenecker, Doris; Vettorazzi, Sabine; Bauer, Mandy; Mauser, Lea; Amann, Sabine; Jall, Sigrid; Fischer, Katrin; Esterbauer, Harald; Müller, Timo D; Tschöp, Matthias H; Magnes, Christoph; Haybaeck, Johannes; Scherer, Thomas; Bordag, Natalie; Tuckermann, Jan P; Moriggl, Richard

2017-02-01

Glucocorticoids (GCs) are important regulators of systemic energy metabolism, and aberrant GC action is linked to metabolic dysfunctions. Yet, the extent to which normal and pathophysiological energy metabolism depend on the GC receptor (GR) in adipocytes remains unclear. Here, we demonstrate that adipocyte GR deficiency in mice significantly impacts systemic metabolism in different energetic states. Plasma metabolomics and biochemical analyses revealed a marked global effect of GR deficiency on systemic metabolite abundance and, thus, substrate partitioning in fed and fasted states. This correlated with a decreased lipolytic capacity of GR-deficient adipocytes under postabsorptive and fasting conditions, resulting from impaired signal transduction from β-adrenergic receptors to adenylate cyclase. Upon prolonged fasting, the impaired lipolytic response resulted in abnormal substrate utilization and lean mass wasting. Conversely, GR deficiency attenuated aging-/diet-associated obesity, adipocyte hypertrophy, and liver steatosis. Systemic glucose tolerance was improved in obese GR-deficient mice, which was associated with increased insulin signaling in muscle and adipose tissue. We conclude that the GR in adipocytes exerts central but diverging roles in the regulation of metabolic homeostasis depending on the energetic state. The adipocyte GR is indispensable for the feeding-fasting transition but also promotes adiposity and associated metabolic disorders in fat-fed and aged mice. © 2017 by the American Diabetes Association.

Adiposity and metabolic dysfunction in polycystic ovary syndrome.

PubMed

Sam, Susan

2015-02-01

Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-age women and is associated with a high risk for metabolic disorders. Adiposity and insulin resistance are two prevalent conditions in PCOS and the likely culprits for the heightened metabolic risk. Up to 60% of women with PCOS are considered to be overweight or obese, and even among non-obese women with PCOS there is an increased accumulation of adipose tissue in abdominal depots. Insulin resistance in PCOS is unique and independent of obesity, as even non-obese women with this condition are frequently insulin resistant. However, obesity substantially aggravates the insulin resistance and the metabolic and reproductive abnormalities in women with PCOS. Recently, it has been shown that many aspects of adipose tissue function in PCOS are abnormal, and these abnormalities likely predispose to development of insulin resistance even in the absence of obesity. This review provides an overview of these abnormalities and their impact on development of metabolic disorders. At the end, an overview of the therapeutic options for management of adiposity and its complications in PCOS are discussed.

Mass spectrometry-based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders.

PubMed

Luan, Hemi; Wang, Xian; Cai, Zongwei

2017-11-12

Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the investigation of underlying mechanism of therapeutic strategies. © 2017 Wiley Periodicals, Inc.

From “Kidneys Govern Bones” to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science

PubMed Central

Zou, Xin-Rong

2016-01-01

Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of “Kidneys Govern Bones.” Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes. PMID:27668003

Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis.

PubMed

He, Congcong; Bassik, Michael C; Moresi, Viviana; Sun, Kai; Wei, Yongjie; Zou, Zhongju; An, Zhenyi; Loh, Joy; Fisher, Jill; Sun, Qihua; Korsmeyer, Stanley; Packer, Milton; May, Herman I; Hill, Joseph A; Virgin, Herbert W; Gilpin, Christopher; Xiao, Guanghua; Bassel-Duby, Rhonda; Scherer, Philipp E; Levine, Beth

2012-01-18

Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control. During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism. Moreover, in animal models, autophagy protects against diseases such as cancer, neurodegenerative disorders, infections, inflammatory diseases, ageing and insulin resistance. Here we show that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice. To investigate the role of exercise-mediated autophagy in vivo, we generated mutant mice that show normal levels of basal autophagy but are deficient in stimulus (exercise- or starvation)-induced autophagy. These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent stimulus-induced disruption of the BCL2-beclin-1 complex and autophagy activation. BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-induced glucose intolerance. Thus, exercise induces autophagy, BCL2 is a crucial regulator of exercise- (and starvation)-induced autophagy in vivo, and autophagy induction may contribute to the beneficial metabolic effects of exercise.

Fanconi Anemia complementation group C protein in metabolic disorders.

PubMed

Nepal, Manoj; Ma, Chi; Xie, Guoxiang; Jia, Wei; Fei, Peiwen

2018-06-21

Given importance of 22-Fanconi Anemia (FA) proteins together to act in a signaling pathway in preventing deleterious clinical symptoms, e.g. severe bone marrow failure, congenital defects, an early onset of aging and cancer, studies on each FA protein become increasingly attractive. However, an unbiased and systematic investigation of cellular effects resulting from each FA protein is missing. Here, we report roles of FA complementation C group protein (FANCC) in the protection from metabolic disorders. This study was prompted by the diabetes-prone feature displayed in FANCC knockout mice, which is not typically shown in patients with FA. We found that in cells expressing FANCC at different levels, there are representative alterations in metabolites associated with aging (glycine, citrulline, ornithine, L-asparagine, L-tyrosine, L-arginine, L-glutamine, L-leucine, L-isoleucine, L-valine, L-proline and L-alanine), Diabetes Mellitus (DM) (carbon monoxide, collagens, fatty acids, D-glucose, fumaric acid, 2-oxoglutaric acid, C3), inflammation (inosine, L-arginine, L-isoleucine, L-leucine, L-lysine, L-phenylalanine, hypoxanthine, L-methionine), and cancer ( L-methionine, sphingomyelin, acetyl-L-carnitine, L-aspartic acid, L-glutamic acid, niacinamide, phospho-rylethanolamine). We also found that FANCC can act in an FA-pathway-independent manner in tumor suppression. Collectively, featured-metabolic alterations are readouts of functional mechanisms underlying reduced tumorigenicity driven by FANCC, demonstrating close links among cancer, aging, inflammation and DM.

High-resolution detection of 13C multiplets from the conscious mouse brain by ex vivo NMR spectroscopy

PubMed Central

Marin-Valencia, Isaac; Good, Levi B.; Ma, Qian; Jeffrey, F. Mark; Malloy, Craig R.; Pascual, Juan M.

2011-01-01

Glucose readily supplies the brain with the majority of carbon needed to sustain neurotransmitter production and utilization., The rate of brain glucose metabolism can be computed using 13C nuclear magnetic resonance (NMR) spectroscopy by detecting changes in 13C contents of products generated by cerebral metabolism. As previously observed, scalar coupling between adjacent 13C carbons (multiplets) can provide additional information to 13C contents for the computation of metabolic rates. Most NMR studies have been conducted in large animals (often under anesthesia) because the mass of the target organ is a limiting factor for NMR. Yet, despite the challengingly small size of the mouse brain, NMR studies are highly desirable because the mouse constitutes a common animal model for human neurological disorders. We have developed a method for the ex vivo resolution of NMR multiplets arising from the brain of an awake mouse after the infusion of [1,6-13C2]glucose. NMR spectra obtained by this method display favorable signal-to-noise ratios. With this protocol, the 13C multiplets of glutamate, glutamine, GABA and aspartate achieved steady state after 150 min. The method enables the accurate resolution of multiplets over time in the awake mouse brain. We anticipate that this method can be broadly applicable to compute brain fluxes in normal and transgenic mouse models of neurological disorders. PMID:21946227

78 FR 63224 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

...: Endocrinologic and Metabolic Drugs Advisory Committee. General Function of the Committee: To provide advice and... disorder caused by the absence or malfunctioning of an enzyme involved in an important metabolic pathway...

38 CFR 4.130 - Schedule of ratings-mental disorders.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Alzheimer's type 9326Dementia due to other neurologic or general medical conditions (endocrine disorders, metabolic disorders, Pick's disease, brain tumors, etc.) or that are substance-induced (drugs, alcohol...

Bipolar Disorder.

PubMed

Miller, Thomas H

2016-06-01

Bipolar disorder is a chronic mental health disorder that is frequently encountered in primary care. Many patients with depression may actually have bipolar disorder. The management of bipolar disorder requires proper diagnosis and awareness or referral for appropriate pharmacologic therapy. Patients with bipolar disorder require primary care management for comorbidities such as cardiovascular and metabolic disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Endocrine causes of nonalcoholic fatty liver disease

PubMed Central

Marino, Laura; Jornayvaz, François R

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed. PMID:26494962

Facing acid–base disorders in the third millennium – the Stewart approach revisited

PubMed Central

Kishen, R; Honoré, Patrick M; Jacobs, R; Joannes-Boyau, O; De Waele, E; De Regt, J; Van Gorp, V; Boer, W; Spapen, HD

2014-01-01

Acid–base disorders are common in the critically ill. Most of these disorders do not cause harm and are self-limiting after appropriate resuscitation and management. Unfortunately, clinicians tend to think about an acid–base disturbance as a “disease” and spend long hours effectively treating numbers rather than the patient. Moreover, a sizable number of intensive-care physicians experience difficulties in interpreting the significance of or understanding the etiology of certain forms of acid–base disequilibria. Traditional tools for interpreting acid–base disorders may not be adequate for analyzing the complex nature of these metabolic abnormalities. Inappropriate interpretation may also lead to wrong clinical conclusions and incorrectly influence clinical management (eg, bicarbonate therapy for metabolic acidosis in different clinical situations). The Stewart approach, based on physicochemical principles, is a robust physiological concept that can facilitate the interpretation and analysis of simple, mixed, and complex acid–base disorders, thereby allowing better diagnosis of the cause of the disturbance and more timely treatment. However, as the concept does not attach importance to plasma bicarbonate, clinicians may find it complicated to use in their daily clinical practice. This article reviews various approaches to interpreting acid–base disorders and suggests the integration of base-excess and Stewart approach for a better interpretation of these metabolic disorders. PMID:24959091

Toxigenic and metabolic causes of ketosis and ketoacidotic syndromes.

PubMed

Cartwright, Martina M; Hajja, Waddah; Al-Khatib, Sofian; Hazeghazam, Maryam; Sreedhar, Dharmashree; Li, Rebecca Na; Wong-McKinstry, Edna; Carlson, Richard W

2012-10-01

Ketoacidotic syndromes are frequently encountered in acute care medicine. This article focuses on ketosis and ketoacidotic syndromes associated with intoxications, alcohol abuse, starvation, and certain dietary supplements as well as inborn errors of metabolism. Although all of these various processes are characterized by the accumulation of ketone bodies and metabolic acidosis, there are differences in the mechanisms, clinical presentations, and principles of therapy for these heterogeneous disorders. Pathophysiologic mechanisms that account for these disorders are presented, as well as guidance regarding identification and management. Copyright © 2012 Elsevier Inc. All rights reserved.

Positron emission tomography assessment of effects of benzodiazepines on regional glucose metabolic rate in patients with anxiety disorder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchsbaum, M.S.; Wu, J.; Haier, R.

1987-06-22

Patients with generalized anxiety disorder (n = 18) entered a 21-day, double-blind, placebo-controlled random assignment trial of clorazepate. Positron emission tomography with YF-deoxyglucose was carried out before and after treatment. Decreases in glucose metabolic rate in visual cortex and relative increases in the basal ganglia and thalamus were found. A correlation between regional changes in metabolic rate and regional benzodiazepine receptor binding density from other human autopsy studies was observed; brain regions highest in receptor density showed the greatest decrease in rate.

Sodium Butyrate Protects -Against High Fat Diet-Induced Cardiac Dysfunction and Metabolic Disorders in Type II Diabetic Mice.

PubMed

Zhang, Ling; Du, Jianfeng; Yano, Naohiro; Wang, Hao; Zhao, Yu Tina; Dubielecka, Patrycja M; Zhuang, Shougang; Chin, Y Eugene; Qin, Gangjian; Zhao, Ting C

2017-08-01

Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in Type II diabetes and obesity remains unknown. Here, we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively. Glucose intolerance, metabolic parameters, cardiac function, and remodeling were assessed. Histological analysis and cellular signaling were examined at 24 weeks following euthanization of mice. HFD-fed mice demonstrated myocardial dysfunction and profound interstitial fibrosis, which were attenuated by HDAC inhibition. HFD-induced metabolic syndrome features insulin resistance, obesity, hyperinsulinemia, hyperglycemia, lipid accumulations, and cardiac hypertrophy, these effects were prevented by HDAC inhibition. Furthermore, HDAC inhibition attenuated myocyte apoptosis, reduced production of reactive oxygen species, and increased angiogenesis in the HFD-fed myocardium. Notably, HFD induced decreases in MKK3, p38, p38 regulated/activated protein kinase (PRAK), and Akt-1, but not p44/42 phosphorylation, which were prevented by HDAC inhibition. These results suggest that HDAC inhibition plays a critical role to preserve cardiac performance and mitigate metabolic disorders in obesity and diabetes, which is associated with MKK3/p38/PRAK pathway. The study holds promise in developing a new therapeutic strategy in the treatment of Type II diabetic-induced heart failure and metabolic disorders. J. Cell. Biochem. 118: 2395-2408, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Pharmacologically-induced metabolic acidosis: a review.

PubMed

Liamis, George; Milionis, Haralampos J; Elisaf, Moses

2010-05-01

Metabolic acidosis may occasionally develop in the course of treatment with drugs used in everyday clinical practice, as well as with the exposure to certain chemicals. Drug-induced metabolic acidosis, although usually mild, may well be life-threatening, as in cases of lactic acidosis complicating antiretroviral therapy or treatment with biguanides. Therefore, a detailed medical history, with special attention to the recent use of culprit medications, is essential in patients with acid-base derangements. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on the acid-base status. In this review, we evaluate relevant literature with regard to metabolic acidosis associated with specific drug treatment, and discuss the clinical setting and underlying pathophysiological mechanisms. These mechanisms involve renal inability to excrete the dietary H+ load (including types I and IV renal tubular acidoses), metabolic acidosis owing to increased H+ load (including lactic acidosis, ketoacidosis, ingestion of various substances, administration of hyperalimentation solutions and massive rhabdomyolysis) and metabolic acidosis due to HCO3- loss (including gastrointestinal loss and type II renal tubular acidosis). Determinations of arterial blood gases, the serum anion gap and, in some circumstances, the serum osmolar gap are helpful in delineating the pathogenesis of the acid-base disorder. In all cases of drug-related metabolic acidosis, discontinuation of the culprit medications and avoidance of readministration is advised.

The TreadWheel: Interval Training Protocol for Gently Induced Exercise in Drosophila melanogaster.

PubMed

Lowman, Kelsey E; Wyatt, Brélahn J; Cunneely, Owen P; Reed, Laura K

2018-06-08

The incidence of complex metabolic diseases has increased as a result of a widespread transition towards lifestyles of increased caloric intake and lowered activity levels. These multifactorial diseases arise from a combination of genetic, environmental, and behavioral factors. One such complex disease is Metabolic Syndrome (MetS), which is a cluster of metabolic disorders, including hypertension, hyperglycemia, and abdominal obesity. Exercise and dietary intervention are the primary treatments recommended by doctors to mitigate obesity and its subsequent metabolic diseases. Exercise intervention, in particular aerobic interval training, stimulates favorable changes in the common risk factors for Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD), and other conditions. With the influx of evidence describing the therapeutic effect exercise has on metabolic health, establishing a system that models exercise in a controlled setting provides a valuable tool for assessing the effects of exercise in an experimental context. Drosophila melanogaster is a great tool for investigating the physiological and molecular changes that result from exercise intervention. The flies have short lifespans and similar mechanisms of metabolizing nutrients when compared to humans. To induce exercise in Drosophila, we developed a machine called the TreadWheel, which utilizes the fly's innate, negative geotaxis tendency to gently induce climbing. This enables researchers to perform experiments on large cohorts of genetically diverse flies to better understand the genotype-by-environment interactions underlying the effects of exercise on metabolic health.

Metabolomics identifies perturbations in amino acid metabolism in the prefrontal cortex of the learned helplessness rat model of depression.

PubMed

Zhou, Xinyu; Liu, Lanxiang; Zhang, Yuqing; Pu, Juncai; Yang, Lining; Zhou, Chanjuan; Yuan, Shuai; Zhang, Hanping; Xie, Peng

2017-02-20

Major depressive disorder is a serious psychiatric condition associated with high rates of suicide and is a leading cause of health burden worldwide. However, the underlying molecular mechanisms of major depression are still essentially unclear. In our study, a non-targeted gas chromatography-mass spectrometry-based metabolomics approach was used to investigate metabolic changes in the prefrontal cortex of the learned helplessness (LH) rat model of depression. Body-weight measurements and behavioral tests including the active escape test, sucrose preference test, forced swimming test, elevated plus-maze and open field test were used to assess changes in the behavioral spectrum after inescapable footshock stress. Rats in the stress group exhibited significant learned helpless and depression-like behaviors, while without any significant change in anxiety-like behaviors. Using multivariate and univariate statistical analysis, a total of 18 differential metabolites were identified after the footshock stress protocol. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis. "Amino Acid Metabolism, Molecule Transport, Small Molecule Biochemistry" was the most significantly altered network in the LH model. Amino acid metabolism, particularly glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, was significantly perturbed in the prefrontal cortex of LH rats. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Sexual dimorphism of lipid metabolism in very long-chain acyl-CoA dehydrogenase deficient (VLCAD-/-) mice in response to medium-chain triglycerides (MCT).

PubMed

Tucci, Sara; Flögel, Ulrich; Spiekerkoetter, Ute

2015-07-01

Medium-chain triglycerides (MCT) are widely applied in the treatment of long-chain fatty acid oxidation disorders. Previously it was shown that long-term MCT supplementation strongly affects lipid metabolism in mice. We here investigate sex-specific effects in mice with very-long-chain-acyl-CoA dehydrogenase (VLCAD) deficiency in response to a long-term MCT modified diet. We quantified blood lipids, acylcarnitines, glucose, insulin and free fatty acids, as well as tissue triglycerides in the liver and skeletal muscle under a control and an MCT diet over 1 year. In addition, visceral and hepatic fat content and muscular intramyocellular lipids (IMCL) were assessed by in vivo(1)H magnetic resonance spectroscopy (MRS) techniques. The long-term application of an MCT diet induced a marked alteration of glucose homeostasis. However, only VLCAD-/- female mice developed a severe metabolic syndrome characterized by marked insulin resistance, dyslipidemia, severe hepatic and visceral steatosis, whereas VLCAD-/- males seemed to be protected and only presented with milder insulin resistance. Moreover, the highly saturated MCT diet is associated with a decreased hepatic stearoyl-CoA desaturase 1 (SCD1) activity in females aggravating the harmful effects of a saturated MCT diet. Long-term MCT supplementation deeply affects lipid metabolism in a sexual dimorphic manner resulting in a severe metabolic syndrome only in female mice. These findings are striking since the first signs of insulin resistance already occur in female VLCAD-/- mice during their reproductive period. How these metabolic adaptations are finally regulated needs to be determined. More important, the relevance of these findings for humans under these dietary modifications needs to be investigated. Copyright © 2015 Elsevier B.V. All rights reserved.

Lateral hypothalamic area deep brain stimulation for refractory obesity: a pilot study with preliminary data on safety, body weight, and energy metabolism

PubMed Central

Whiting, Donald M.; Tomycz, Nestor D.; Bailes, Julian; De Jonge, Lilian; Lecoultre, Virgile; Wilent, Bryan; Alcindor, Dunbar; Prostko, E. Richard; Cheng, Boyle C.; Angle, Cynthia; Cantella, Diane; Whiting, Benjamin B.; Mizes, J. Scott; Finnis, Kirk W.; Ravussin, Eric; Oh, Michael Y.

2017-01-01

Object Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity. The authors present the 2-year safety results as well as early efficacy and metabolic effects in 3 patients undergoing bilateral LHA DBS in the first study of this approach in humans. Methods Three patients meeting strict criteria for intractable obesity, including failed bariatric surgery, under-went bilateral implantation of LHA DBS electrodes as part of an institutional review board– and FDA-approved pilot study. The primary focus of the study was safety; however, the authors also received approval to collect data on early efficacy including weight change and energy metabolism. Results No serious adverse effects, including detrimental psychological consequences, were observed with continuous LHA DBS after a mean follow-up of 35 months (range 30–39 months). Three-dimensional nonlinear transformation of postoperative imaging superimposed onto brain atlas anatomy was used to confirm and study DBS contact proximity to the LHA. No significant weight loss trends were seen when DBS was programmed using standard settings derived from movement disorder DBS surgery. However, promising weight loss trends have been observed when monopolar DBS stimulation has been applied via specific contacts found to increase the resting metabolic rate measured in a respiratory chamber. Conclusions Deep brain stimulation of the LHA may be applied safely to humans with intractable obesity. Early evidence for some weight loss under metabolically optimized settings provides the first “proof of principle” for this novel antiobesity strategy. A larger follow-up study focused on efficacy along with a more rigorous metabolic analysis is planned to further explore the benefits and therapeutic mechanism behind this investigational therapy. PMID:23560573

Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis.

PubMed

Russell, James C; Proctor, Spencer D

2006-01-01

Cardiovascular disease, the leading cause of death in much of the modern world, is the common symptomatic end stage of a number of distinct diseases and, therefore, is multifactorial and polygenetic in character. The two major underlying causes are disorders of lipid metabolism and metabolic syndrome. The ability to develop preventative and ameliorative treatments will depend on animal models that mimic human disease processes. The focus of this review is to identify suitable animal models and insights into cardiovascular disease achieved to date using such models. The ideal animal model of cardiovascular disease will mimic the human subject metabolically and pathophysiologically, will be large enough to permit physiological and metabolic studies, and will develop end-stage disease comparable to those in humans. Given the complex multifactorial nature of cardiovascular disease, no one species will be suitable for all studies. Potential larger animal models are problematic due to cost, ethical considerations, or poor pathophysiological comparability to humans. Rabbits require high-cholesterol diets to develop cardiovascular disease, and there are no rabbit models of metabolic syndrome. Spontaneous mutations in rats provide several complementary models of obesity, hyperlipidemia, insulin resistance, and type 2 diabetes, one of which spontaneously develops cardiovascular disease and ischemic lesions. The mouse, like normal rats, is characteristically resistant to cardiovascular disease, although genetically altered strains respond to cholesterol feeding with atherosclerosis, but not with end-stage ischemic lesions. The most useful and valid species/strains for the study of cardiovascular disease appear to be small rodents, rats, and mice. This fragmented field would benefit from a consensus on well-characterized appropriate models for the study of different aspects of cardiovascular disease and a renewed emphasis on the biology of underlying diseases.

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

PubMed

Vancampfort, Davy; Stubbs, Brendon

2017-12-15

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

Genome-wide association study identifies multiple loci influencing human serum metabolite levels

PubMed Central

Kettunen, Johannes; Tukiainen, Taru; Sarin, Antti-Pekka; Ortega-Alonso, Alfredo; Tikkanen, Emmi; Lyytikäinen, Leo-Pekka; Kangas, Antti J; Soininen, Pasi; Würtz, Peter; Silander, Kaisa; Dick, Danielle M; Rose, Richard J; Savolainen, Markku J; Viikari, Jorma; Kähönen, Mika; Lehtimäki, Terho; Pietiläinen, Kirsi H; Inouye, Michael; McCarthy, Mark I; Jula, Antti; Eriksson, Johan; Raitakari, Olli T; Salomaa, Veikko; Kaprio, Jaakko; Järvelin, Marjo-Riitta; Peltonen, Leena; Perola, Markus; Freimer, Nelson B; Ala-Korpela, Mika; Palotie, Aarno; Ripatti, Samuli

2013-01-01

Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P < 2.31 × 10−10) at 31 loci, including 11 for which there have not been previous reports of associations to a metabolic trait or disorder. Analyses of Finnish twin pairs suggested that the metabolic measures reported here show higher heritability than comparable conventional metabolic phenotypes. In accordance with our expectations, SNPs at the 31 loci associated with individual metabolites account for a greater proportion of the genetic component of trait variance (up to 40%) than is typically observed for conventional serum metabolic phenotypes. The identification of such associations may provide substantial insight into cardiometabolic disorders. PMID:22286219

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women.

PubMed

Diamanti-Kandarakis, Evanthia; Papalou, Olga; Kandaraki, Eleni A; Kassi, Georgia

2017-02-01

Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. © 2017 European Society of Endocrinology.

Posttraumatic Stress Disorder, Cardiovascular and Metabolic Disease: A Review of the Evidence

PubMed Central

Dedert, Eric A.; Calhoun, Patrick S.; Watkins, Lana L.; Sherwood, Andrew; Beckham, Jean C.

2011-01-01

Background Posttraumatic stress disorder (PTSD) is a significant risk factor for cardiovascular and metabolic disease. Purpose The purpose of the current review is to evaluate the evidence suggesting that PTSD increases cardiovascular and metabolic risk factors, and to identify possible biomarkers and psychosocial characteristics and behavioral variables that are associated with these outcomes. Methods A systematic literature search in the period of 2002–2009 for PTSD, cardiovascular disease, and metabolic disease was conducted. Results The literature search yielded 78 studies on PTSD and cardiovascular/metabolic disease and biomarkers. Conclusions Although the available literature suggests an association of PTSD with cardiovascular disease and biomarkers, further research must consider potential confounds, incorporate longitudinal designs, and conduct careful PTSD assessments in diverse samples to address gaps in the research literature. Research on metabolic disease and biomarkers suggests an association with PTSD, but has not progressed as far as the cardiovascular research. PMID:20174903

1H-NMR, 1H-NMR T2-edited, and 2D-NMR in bipolar disorder metabolic profiling.

PubMed

Sethi, Sumit; Pedrini, Mariana; Rizzo, Lucas B; Zeni-Graiff, Maiara; Mas, Caroline Dal; Cassinelli, Ana Cláudia; Noto, Mariane N; Asevedo, Elson; Cordeiro, Quirino; Pontes, João G M; Brasil, Antonio J M; Lacerda, Acioly; Hayashi, Mirian A F; Poppi, Ronei; Tasic, Ljubica; Brietzke, Elisa

2017-12-01

The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. Metabolomic profiling, employing 1 H-NMR, 1 H-NMR T 2 -edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed. The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic acid, L-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.

Maternal High-Fat Diet Programming of the Neuroendocrine System and Behavior

PubMed Central

Sullivan, Elinor L.; Riper, Kellie M.; Lockard, Rachel; Valleau, Jeanette C.

2015-01-01

Maternal obesity, metabolic state, and diet during gestation have profound effects on offspring development. The prevalence of neurodevelopmental and mental health disorders has risen rapidly in the last several decades in parallel with the rise in obesity rates. Evidence from epidemiological studies indicates that maternal obesity and metabolic complications increase the risk of offspring developing behavioral disorders such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and schizophrenia. Animal models show that a maternal diet high in fat similarly disrupts behavioral programming of offspring, with animals showing social impairments, increased anxiety and depressive behaviors, reduced cognitive development, and hyperactivity. Maternal obesity, metabolic conditions, and high fat diet consumption increase maternal leptin, insulin, glucose, triglycerides, and inflammatory cytokines. This leads to increased risk of placental dysfunction, and altered fetal neuroendocrine development. Changes in brain development that likely contribute to the increased risk of behavioral and mental health disorders include increased inflammation in the brain, as well as alterations in the serotonergic system, dopaminergic system and hypothalamic pituitary adrenal (HPA) axis. PMID:25913366

CEREBRAL BLOOD FLOW AND METABOLISM IN ANXIETY AND ANXIETY DISORDERS

PubMed Central

Mathew, Roy J.

1994-01-01

Anxiety disorders are some of the commonest psychiatric disorders and anxiety commonly co-exists with other psychiatric conditions. Anxiety can also be a normal emotion. Thus, study of the neurobiological effects of anxiety is of considerable significance. In the normal brain, cerebral blood flow (CBF) and metabolism (CMR) serve as indices of brain function. CBF/CMR research is expected to provide new insight into alterations in brain function in anxiety disorders and other psychiatric disorders. Possible associations between stress I anxiety I panic and cerebral ischemia I stroke give additional significance to the effects of anxiety on CBF. With the advent of non-invasive techniques, study of CBF/CMR in anxiety disorders became easier. A large numbers of research reports are available on the effects of stress, anxiety and panic on CBF/CMR in normals and anxiety disorder patients. This article reviews the available human research on this topic. PMID:21743685

Altered Circadian Timing System-Mediated Non-Dipping Pattern of Blood Pressure and Associated Cardiovascular Disorders in Metabolic and Kidney Diseases

PubMed Central

Nishiyama, Akira

2018-01-01

The morning surge in blood pressure (BP) coincides with increased cardiovascular (CV) events. This strongly suggests that an altered circadian rhythm of BP plays a crucial role in the development of CV disease (CVD). A disrupted circadian rhythm of BP, such as the non-dipping type of hypertension (i.e., absence of nocturnal BP decline), is frequently observed in metabolic disorders and chronic kidney disease (CKD). The circadian timing system, controlled by the central clock in the suprachiasmatic nucleus of the hypothalamus and/or by peripheral clocks in the heart, vasculature, and kidneys, modulates the 24 h oscillation of BP. However, little information is available regarding the molecular and cellular mechanisms of an altered circadian timing system-mediated disrupted dipping pattern of BP in metabolic disorders and CKD that can lead to the development of CV events. A more thorough understanding of this pathogenesis could provide novel therapeutic strategies for the management of CVD. This short review will address our and others’ recent findings on the molecular mechanisms that may affect the dipping pattern of BP in metabolic dysfunction and kidney disease and its association with CV disorders. PMID:29385702

Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets?

PubMed Central

Masino, Susan A.; Geiger, Jonathan D.

2015-01-01

Abnormal neuronal signaling caused by metabolic changes characterizes several neurological disorders, and in some instances metabolic interventions provide therapeutic benefits. Indeed, altering metabolism either by fasting or by maintaining a low-carbohydrate (ketogenic) diet might reduce epileptic seizures and offer neuroprotection in part because the diet increases mitochondrial biogenesis and brain energy levels. Here we focus on a novel hypothesis that a ketogenic diet-induced change in energy metabolism increases levels of ATP and adenosine, purines that are critically involved in neuron–glia interactions, neuromodulation and synaptic plasticity. Enhancing brain bioenergetics (ATP) and increasing levels of adenosine, an endogenous anticonvulsant and neuroprotective molecule, might help with understanding and treating a variety of neurological disorders. PMID:18471903

The degree of cycle irregularity correlates with the grade of endocrine and metabolic disorders in PCOS patients.

PubMed

Strowitzki, Thomas; Capp, Edison; von Eye Corleta, Helena

2010-04-01

PCOS (polycystic ovarian syndrome) is a clinically heterogeneous endocrine disorder which affects up to 4-10% of women of reproductive age. A standardized definition is still difficult because of a huge variety of different phenotypes. The aim of this study was to evaluate possible correlations between the degree of cycle irregularity and the grade of endocrine and metabolic abnormalities. A cross-sectional study was carried out. Hyperandrogenic and/or hirsute women with regular menstrual cycles and polycystic ovaries on ultrasound (PCOS eumenorr, n=45), PCOS patients with oligomenorrhea (PCOS oligo, n=42) and PCOS patients with amenorrhea (PCOS amenorr, n=31) were recruited from the Department of Gynecological Endocrinology and Reproductive Medicine of the Women's University Hospital Heidelberg (Heidelberg, Germany). Normocyclic patients demonstrated significantly better metabolic parameters (BMI, fasting insulin, HOMA-IR) than patients with oligo/amenorrhea. Hormonal parameters (LH, FSH, FAI and testosterone) were significantly different between patients with different menstrual patterns and patients with regular cycles. Determining the degree of cycle irregularity as a simple clinical parameter might be a valuable instrument to estimate the degree of metabolic and endocrine disorders. Emphasis should be given to those parameters as a first step to characterize PCOS patients with a risk of endocrine and metabolic disorders leading to consequent detailed examination. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Potential role of liver enzymes levels as predictor markers of glucose metabolism disorders in Tunisian population.

PubMed

Bouhajja, Houda; Abdelhedi, Rania; Amouri, Ali; Hadj Kacem, Faten; Marrakchi, Rim; Safi, Wajdi; Mrabet, Houcem; Chtourou, Lassaad; Charfi, Nadia; Fourati, Mouna; Bensassi, Salwa; Jamoussi, Kamel; Abid, Mohamed; Ayadi, Hammadi; Feki, Mouna Mnif; Elleuch, Noura Bougacha

2018-03-10

The relationship between liver enzymes and type 2 diabetes (T2D) risk is inconclusive. We aimed to evaluate the association between liver markers and risk of carbohydrate metabolism disorders and their discriminatory power for T2D prediction. This cross-sectional study enrolled 216 participants classified as normoglycemic, prediabetes, newly-diagnosed diabetes and diagnosed diabetes. All participants underwent anthropometric and biochemical measurements. The relationship between hepatic enzymes and glucose metabolism markers was evaluated by ANCOVA analyses. The associations between liver enzymes and incident carbohydrate metabolism disorders were analyzed through logistic regression and their discriminatory capacity for T2D by receiver operating characteristic (ROC) analysis. High alkaline phosphatase (AP), alanine aminotransferase (ALT), γ-glutamyltransferase (γGT) and aspartate aminotrasferase (AST) levels were independently related to decreased insulin sensitivity. Interestingly, higher AP level was significantly associated with increased risk of prediabetes (p=0.017), newly-diagnosed diabetes (p=0.004) and T2D (p=0.007). Elevated γGT level was an independent risk factor for T2D (p=0.032) and undiagnosed-T2D (p=0.010) in prediabetic and normoglycemic subjects, respectively. In ROC analysis, AP was a powerful predictor of incident diabetes and significantly improved T2D prediction. Liver enzymes within normal range, specifically AP levels, are associated with increased risk of carbohydrate metabolism disorders and significantly improved T2D prediction.

Neuroprotective effects of leptin in the context of obesity and metabolic disorders.

PubMed

Davis, Cecilia; Mudd, Jeremy; Hawkins, Meredith

2014-12-01

As the population of the world ages, the prevalence of neurodegenerative disease continues to rise, accompanied by increases in disease burden related to obesity and metabolic disorders. Thus, it will be essential to develop tools for preventing and slowing the progression of these major disease entities. Epidemiologic studies have shown strong associations between obesity, metabolic dysfunction, and neurodegeneration, while animal models have provided insights into the complex relationships between these conditions. Experimentally, the fat-derived hormone leptin has been shown to act as a neuroprotective agent in various animal models of dementia, toxic insults, ischemia/reperfusion, and other neurodegenerative processes. Specifically, leptin minimizes neuronal damage induced by neurotoxins and pro-apoptotic conditions. Leptin has also demonstrated considerable promise in animal models of obesity and metabolic disorders via modulation of glucose homeostasis and energy intake. However, since obesity is known to induce leptin resistance, we hypothesize that resistance to the neuroprotective effects of leptin contributes to the pathogenesis of obesity-associated neurodegenerative diseases. This review aims to explore the literature pertinent to the role of leptin in the protection of neurons from the toxic effects of aging, obesity and metabolic disorders, to investigate the physiological state of leptin resistance and its causes, and to consider how leptin might be employed therapeutically in the prevention and treatment of neurodegenerative disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders.

PubMed

Augustin, Katrin; Khabbush, Aziza; Williams, Sophie; Eaton, Simon; Orford, Michael; Cross, J Helen; Heales, Simon J R; Walker, Matthew C; Williams, Robin S B

2018-01-01

High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional brain imaging of cognitive dysfunction in Parkinson's disease.

PubMed

Hirano, Shigeki; Shinotoh, Hitoshi; Eidelberg, David

2012-10-01

Multiple factors are involved in the development of cognitive impairment in Parkinson's disease (PD) and related disorders. Notably, several underlying factors, such as monoaminergic dysfunction, Lewy body pathology, Alzheimer disease-like pathology and cerebrovascular disease are implied in the PD pathophysiology of cognitive impairment. The mesocortical dopaminergic system is associated with executive functions which are frequently affected in PD and are influenced by local levodopa concentration, dopamine metabolism and baseline performance status. The ventral striatum and frontal cortex are associated with impulse control disorders reported in PD patients treated with dopamine replacement therapy. Cholinergic impairment in PD plays a cardinal role in the development of dementia. Acetylcholinesterase positron emission tomography demonstrates that posterior brain areas are related to cognitive decline in PD patients. Amyloid radiotracer illustrates that patients with PD with severe cognitive impairment were prone to accompanied cortical amyloid deposition. Metabolism/perfusion change associated with cognitive impairment in PD, so-called PD related cognitive pattern, is characterised by reduced frontoparietal activity and is an effective way to differentiate and monitor cognitive function of individual PD patients. Cognitive impairment in PD cannot be explained by a single mechanism and is entangled by multiple factors. Imaging studies can unravel each pathological domain, further shed light on the interrelation between different pathomechanisms, not only in PD but also in other dementia related disorders, and thereby integrate its interpretation to apply to therapeutics in individual patients.

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

PubMed

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

2018-04-18

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

Preoperative Medical Evaluation: Part 1: General Principles and Cardiovascular Considerations

PubMed Central

Becker, Daniel E

2009-01-01

A thorough assessment of a patient's medical status is standard practice when dental care is provided. Although this is true for procedures performed under local anesthesia alone, the information gathered may be viewed somewhat differently if the dentist is planning to use sedation or general anesthesia as an adjunct to dental treatment. This article is the first of a 2-part sequence and will address general principles and cardiovascular considerations. A second article will address pulmonary, metabolic, and miscellaneous disorders. PMID:19769423

Role of Endoplasmic Reticulum Stress in Metabolic Disease and Other Disorders

PubMed Central

Ozcan, Lale; Tabas, Ira

2012-01-01

Perturbations in the normal functions of the endoplasmic reticulum (ER) trigger a signaling network that coordinates adaptive and apoptotic responses. There is accumulating evidence implicating prolonged ER stress in the development and progression of many diseases, including neurodegeneration, atherosclerosis, type 2 diabetes, liver disease, and cancer. With the improved understanding of the underlying molecular mechanisms, therapeutic interventions that target the ER stress response would be potential strategies to treat various diseases driven by prolonged ER stress. PMID:22248326

Metabolic syndrome among individuals with heroin use disorders on methadone therapy: Prevalence, characteristics, and related factors.

PubMed

Vallecillo, Gabriel; Robles, María José; Torrens, Marta; Samos, Pilar; Roquer, Albert; Martires, Paula K; Sanvisens, Arantza; Muga, Roberto; Pedro-Botet, Juan

2018-01-02

Observational studies have reported a high prevalence of obesity and diabetes in subjects on methadone therapy; there are, however, limited data about metabolic syndrome. The aim of the study was to evaluate the prevalence of metabolic syndrome and related factors in individuals with heroin use disorder on methadone therapy. A cross-sectional study in individuals with heroin use disorder on methadone therapy at a drug abuse outpatient center. Medical examinations and laboratory analyses after a 12-hour overnight fast were recorded. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. One hundred and twenty-two subjects were included, with a mean age of 46.1 ± 9 years, a median body mass index (BMI) of 25.3 kg/m 2 (interquartile range [IQR]: 21.2-28), and 77.9% were men. Median exposure to methadone therapy was 13 years (IQR: 5-20). Overweight and obesity were present in 29.5% and 17.2% of the participants, respectively. Metabolic syndrome components were low high-density lipoprotein (HDL) cholesterol (51.6%), hypertriglyceridemia (36.8%), high blood pressure (36.8%), abdominal obesity (27.0%), and raised blood glucose levels (18.0%). Abdominal obesity was more prevalent in women (52% vs. 20%, P = >0.01) and high blood pressure more prevalent in men (41.1% vs. 22.2%, P = .07). Prevalence of metabolic syndrome was 29.5% (95% confidence interval [CI]: 16.6-31.8). In the multivariate logistic regression analysis, BMI (per 1 kg/m 2 increase odds ratio [OR]: 1.49, 95% CI: 1.27-1.76) and exposure time to methadone therapy (per 5 years of treatment increase OR: 1.38, 95% CI: 1.28-1.48) were associated with metabolic syndrome. Overweight and metabolic syndrome are prevalent findings in individuals with heroin use disorder on methadone therapy. Of specific concern is the association of methadone exposure with metabolic syndrome. Preventive measures and clinical routine screening should be recommended to prevent metabolic syndrome in subjects on methadone therapy.

What Bariatric Surgery Can Teach Us About Endoluminal Treatment of Obesity and Metabolic Disorders.

PubMed

Kaplan, Lee M

2017-04-01

Bariatric surgical procedures, including gastric bypass, vertical sleeve gastrectomy, and biliopancreatic diversion, are the most effective and durable treatments for obesity. In addition, These operations induce metabolic changes that provide weight-independent improvement in type 2 diabetes, fatty liver disease and other metabolic disorders. Initially thought to work by mechanical restriction of food intake or malabsorption of ingested nutrients, these procedures are now known to work through complex changes in neuroendocrine and immune signals emanating from the gut, including peptide hormones, bile acids, vagal nerve activity, and metabolites generated by the gut microbiota, all collaborating to reregulate appetite, food preference, and energy expenditure. Development of less invasive means of achieving these benefits would allow much greater dissemination of effective, gastrointestinal (GI)-targeted therapies for obesity and metabolic disorders. To reproduce the benefits of bariatric surgery, however, these endoscopic procedures and devices will need to mimic the physiological rather than the mechanical effects of these operations. Copyright © 2017 Elsevier Inc. All rights reserved.

Protective effects of vescalagin from pink wax apple [Syzygium samarangense (Blume) Merrill and Perry] fruit against methylglyoxal-induced inflammation and carbohydrate metabolic disorder in rats.

PubMed

Chang, Wen-Chang; Shen, Szu-Chuan; Wu, James Swi-Bea

2013-07-24

The unbalance of glucose metabolism in humans may cause the excessive formation of methylglyoxal (MG), which can react with various biomolecules to form the precursor of advanced glycation end products (AGEs). Vescalagin (VES) is an ellagitannin that alleviates insulin resistance in cell study. Results showed that VES reduced the value of oral glucose tolerance test, cardiovascular risk index, AGEs, and tumor necrosis factor-α contents while increasing C-peptide and d-lactate contents significantly in rats orally administered MG and VES together. The preventive effect of VES on MG-induced inflammation and carbohydrate metabolic disorder in rats was thus proved. On the basis of the experiment data, a mechanism, which involves the increase in d-lactate to retard AGE formation and the decrease in cytokine release to prevent β-cell damage, is proposed to explain the bioactivities of VES in antiglycation and in the alleviation of MG-induced carbohydrate metabolic disorder in rats.

Systematic Review of Metabolic Syndrome Biomarkers: A Panel for Early Detection, Management, and Risk Stratification in the West Virginian Population

PubMed Central

Srikanthan, Krithika; Feyh, Andrew; Visweshwar, Haresh; Shapiro, Joseph I.; Sodhi, Komal

2016-01-01

Introduction: Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic syndrome and this panel can aid in early detection and management of metabolic syndrome in high risk populations, such as in West Virginia. Methods: A literature review was conducted using PubMed, Science Direct, and Google Scholar to search for markers related to metabolic syndrome. Biomarkers searched included adipokines (leptin, adiponectin), neuropeptides (ghrelin), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-10), markers of antioxidant status (OxLDL, PON-1, uric acid), and prothrombic factors (PAI-1). Results: According to the literature, the concentrations of pro-inflammatory cytokines (IL-6, TNF-α), markers of pro-oxidant status (OxLDL, uric acid), and prothrombic factors (PAI-1) were elevated in metabolic syndrome. Additionally, leptin concentrations were found to be elevated in metabolic syndrome as well, likely due to leptin resistance. In contrast, concentrations of anti-inflammatory cytokines (IL-10), ghrelin, adiponectin, and antioxidant factors (PON-1) were decreased in metabolic syndrome, and these decreases also correlated with specific disorders within the cluster. Conclusion: Based on the evidence presented within the literature, the aforementioned biomarkers correlate significantly with metabolic syndrome and could provide a minimally-invasive means for early detection and specific treatment of these disorders. Further research is encouraged to determine the efficacy of applying these biomarkers to diagnosis and treatment in a clinical setting. PMID:26816492

Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health.

PubMed

Bansal, Amita; Henao-Mejia, Jorge; Simmons, Rebecca A

2018-01-01

The incidence of metabolic disorders like type 2 diabetes and obesity continues to increase. In addition to the well-known contributors to these disorders, such as food intake and sedentary lifestyle, recent research in the exposure science discipline provides evidence that exposure to endocrine-disrupting chemicals like bisphenol A and phthalates via multiple routes (e.g., food, drink, skin contact) also contribute to the increased risk of metabolic disorders. Endocrine-disrupting chemicals (EDCs) can disrupt any aspect of hormone action. It is becoming increasingly clear that EDCs not only affect endocrine function but also adversely affect immune system function. In this review, we focus on human, animal, and in vitro studies that demonstrate EDC exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health. These findings highlight how the immune system is emerging as a novel player by which EDCs may mediate their effects on metabolic health. We also discuss studies highlighting mechanisms by which EDCs affect the immune system. Finally, we consider that a better understanding of the immunomodulatory roles of EDCs will provide clues to enhance metabolic function and contribute toward the long-term goal of reducing the burden of environmentally induced diabetes and obesity. Copyright © 2018 Endocrine Society.

The mechanisms of delayed onset type adverse reactions to oseltamivir

PubMed Central

Hama, Rokuro

2016-01-01

Abstract Oseltamivir is recommended for the treatment and prophylaxis of influenza in persons at higher risk for influenza complications such as individuals with diabetes, neuropsychiatric illnesses, and respiratory, cardiac, renal, hepatic or haematological diseases. However, a recent Cochrane review reported that reduction of antibody production, renal disorders, hyperglycaemia, psychiatric disorders, and QT prolongation may be related to oseltamivir use. The underlying mechanisms are reviewed. There is decisive evidence that administration of a clinically compatible dose of oseltamivir in mice challenged by a respiratory syncytial virus (RSV) that lacks a neuraminidase gene showed symptom-relieving effects and inhibition of viral clearance. These effects were accompanied by decreased level of T cell surface sialoglycosphingolipid (ganglioside) GM1 that is regulated by the endogenous neuraminidase in response to viral challenge. Clinical and non-clinical evidence supports the view that the usual dose of oseltamivir suppresses pro-inflammatory cytokines such as interferon-gamma, interleukin-6, and tumour necrosis factor-alpha almost completely with partial suppression of viral shedding in human influenza virus infection experiment. Animal toxicity tests support the clinical evidence with regard to renal and cardiac disorders (bradycardia and QT prolongation) and do not disprove the metabolic effect. Reduction of antibody production and cytokine induction and renal, metabolic, cardiac, and prolonged psychiatric disorders after oseltamivir use may be related to inhibition of the host’s endogenous neuraminidase. While the usual clinical dose of zanamivir may not have this effect, a higher dose or prolonged administration of zanamivir and other neuraminidase inhibitors may induce similar delayed reactions, including reduction of the antibody and/or cytokine production. PMID:27251370

Uric acid as one of the important factors in multifactorial disorders – facts and controversies

PubMed Central

Pasalic, Daria; Marinkovic, Natalija; Feher-Turkovic, Lana

2012-01-01

With considering serum concentration of the uric acid in humans we are observing hyperuricemia and possible gout development. Many epidemiological studies have shown the relationship between the uric acid and different disorders such are obesity, metabolic syndrome, hypertension and coronary artery disease. Clinicians and investigators recognized serum uric acid concentration as very important diagnostic and prognostic factor of many multifactorial disorders. This review presented few clinical conditions which are not directly related to uric acid, but the concentrations of uric acid might have a great impact in observing, monitoring, prognosis and therapy of such disorders. Uric acid is recognized as a marker of oxidative stress. Production of the uric acid includes enzyme xanthine oxidase which is involved in producing of radical-oxigen species (ROS). As by-products ROS have a significant role in the increased vascular oxidative stress and might be involved in atherogenesis. Uric acid may inhibit endothelial function by inhibition of nitric oxide-function under conditions of oxidative stress. Down regulation of nitric oxide and induction of endothelial dysfunction might also be involved in pathogenesis of hypertension. The most important and well evidenced is possible predictive role of uric acid in predicting short-term outcome (mortality) in acute myocardial infarction (AMI) patients and stroke. Nephrolithiasis of uric acid origin is significantly more common among patients with the metabolic syndrome and obesity. On contrary to this, uric acid also acts is an “antioxidant”, a free radical scavenger and a chelator of transitional metal ions which are converted to poorly reactive forms. PMID:22384520

Uric acid as one of the important factors in multifactorial disorders--facts and controversies.

PubMed

Pasalic, Daria; Marinkovic, Natalija; Feher-Turkovic, Lana

2012-01-01

With considering serum concentration of the uric acid in humans we are observing hyperuricemia and possible gout development. Many epidemiological studies have shown the relationship between the uric acid and different disorders such are obesity, metabolic syndrome, hypertension and coronary artery disease. Clinicians and investigators recognized serum uric acid concentration as very important diagnostic and prognostic factor of many multifactorial disorders. This review presented few clinical conditions which are not directly related to uric acid, but the concentrations of uric acid might have a great impact in observing, monitoring, prognosis and therapy of such disorders. Uric acid is recognized as a marker of oxidative stress. Production of the uric acid includes enzyme xanthine oxidase which is involved in producing of radical-oxigen species (ROS). As by-products ROS have a significant role in the increased vascular oxidative stress and might be involved in atherogenesis. Uric acid may inhibit endothelial function by inhibition of nitric oxide-function under conditions of oxidative stress. Down regulation of nitric oxide and induction of endothelial dysfunction might also be involved in pathogenesis of hypertension. The most important and well evidenced is possible predictive role of uric acid in predicting short-term outcome (mortality) in acute myocardial infarction (AMI) patients and stroke. Nephrolithiasis of uric acid origin is significantly more common among patients with the metabolic syndrome and obesity. On contrary to this, uric acid also acts is an "antioxidant", a free radical scavenger and a chelator of transitional metal ions which are converted to poorly reactive forms.

Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy

PubMed Central

Naviaux, J C; Schuchbauer, M A; Li, K; Wang, L; Risbrough, V B; Powell, S B; Naviaux, R K

2014-01-01

Autism spectrum disorders (ASDs) now affect 1–2% of the children born in the United States. Hundreds of genetic, metabolic and environmental factors are known to increase the risk of ASD. Similar factors are known to influence the risk of schizophrenia and bipolar disorder; however, a unifying mechanistic explanation has remained elusive. Here we used the maternal immune activation (MIA) mouse model of neurodevelopmental and neuropsychiatric disorders to study the effects of a single dose of the antipurinergic drug suramin on the behavior and metabolism of adult animals. We found that disturbances in social behavior, novelty preference and metabolism are not permanent but are treatable with antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single dose of suramin (20 mg kg−1 intraperitoneally (i.p.)) given to 6-month-old adults restored normal social behavior, novelty preference and metabolism. Comprehensive metabolomic analysis identified purine metabolism as the key regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic pathways that were disturbed in the MIA model. Two days after treatment, the suramin concentration in the plasma and brainstem was 7.64 μM pmol μl−1 (±0.50) and 5.15 pmol mg−1 (±0.49), respectively. These data show good uptake of suramin into the central nervous system at the level of the brainstem. Most of the improvements associated with APT were lost after 5 weeks of drug washout, consistent with the 1-week plasma half-life of suramin in mice. Our results show that purine metabolism is a master regulator of behavior and metabolism in the MIA model, and that single-dose APT with suramin acutely reverses these abnormalities, even in adults. PMID:24937094

Rescue of Fructose-Induced Metabolic Syndrome by Antibiotics or Faecal Transplantation in a Rat Model of Obesity.

PubMed

Di Luccia, Blanda; Crescenzo, Raffaella; Mazzoli, Arianna; Cigliano, Luisa; Venditti, Paola; Walser, Jean-Claude; Widmer, Alex; Baccigalupi, Loredana; Ricca, Ezio; Iossa, Susanna

2015-01-01

A fructose-rich diet can induce metabolic syndrome, a combination of health disorders that increases the risk of diabetes and cardiovascular diseases. Diet is also known to alter the microbial composition of the gut, although it is not clear whether such alteration contributes to the development of metabolic syndrome. The aim of this work was to assess the possible link between the gut microbiota and the development of diet-induced metabolic syndrome in a rat model of obesity. Rats were fed either a standard or high-fructose diet. Groups of fructose-fed rats were treated with either antibiotics or faecal samples from control rats by oral gavage. Body composition, plasma metabolic parameters and markers of tissue oxidative stress were measured in all groups. A 16S DNA-sequencing approach was used to evaluate the bacterial composition of the gut of animals under different diets. The fructose-rich diet induced markers of metabolic syndrome, inflammation and oxidative stress, that were all significantly reduced when the animals were treated with antibiotic or faecal samples. The number of members of two bacterial genera, Coprococcus and Ruminococcus, was increased by the fructose-rich diet and reduced by both antibiotic and faecal treatments, pointing to a correlation between their abundance and the development of the metabolic syndrome. Our data indicate that in rats fed a fructose-rich diet the development of metabolic syndrome is directly correlated with variations of the gut content of specific bacterial taxa.

Rescue of Fructose-Induced Metabolic Syndrome by Antibiotics or Faecal Transplantation in a Rat Model of Obesity

PubMed Central

Mazzoli, Arianna; Cigliano, Luisa; Venditti, Paola; Walser, Jean-Claude; Widmer, Alex; Baccigalupi, Loredana; Ricca, Ezio; Iossa, Susanna

2015-01-01

A fructose-rich diet can induce metabolic syndrome, a combination of health disorders that increases the risk of diabetes and cardiovascular diseases. Diet is also known to alter the microbial composition of the gut, although it is not clear whether such alteration contributes to the development of metabolic syndrome. The aim of this work was to assess the possible link between the gut microbiota and the development of diet-induced metabolic syndrome in a rat model of obesity. Rats were fed either a standard or high-fructose diet. Groups of fructose-fed rats were treated with either antibiotics or faecal samples from control rats by oral gavage. Body composition, plasma metabolic parameters and markers of tissue oxidative stress were measured in all groups. A 16S DNA-sequencing approach was used to evaluate the bacterial composition of the gut of animals under different diets. The fructose-rich diet induced markers of metabolic syndrome, inflammation and oxidative stress, that were all significantly reduced when the animals were treated with antibiotic or faecal samples. The number of members of two bacterial genera, Coprococcus and Ruminococcus, was increased by the fructose-rich diet and reduced by both antibiotic and faecal treatments, pointing to a correlation between their abundance and the development of the metabolic syndrome. Our data indicate that in rats fed a fructose-rich diet the development of metabolic syndrome is directly correlated with variations of the gut content of specific bacterial taxa. PMID:26244577

Unsolved Problems of Intracellular Noise

NASA Astrophysics Data System (ADS)

Paulsson, Johan

2003-05-01

Many molecules are present at so low numbers per cell that significant fluctuations arise spontaneously. Such `noise' can randomize developmental pathways, disrupt cell cycle control or force metabolites away from their optimal levels. It can also be exploited for non-genetic individuality or, surprisingly, for more reliable and deterministic control. However, in spite of the mechanistic and evolutionary significance of noise, both explicit modeling and implicit verbal reasoning in molecular biology are completely dominated by macroscopic kinetics. Here I discuss some particularly under-addressed issues of noise in genetic and metabolic networks: 1) relations between systematic macro- and mesoscopic approaches; 2) order and disorder in gene expression; 3) autorepression for checking fluctuations; 4) noise suppression by noise; 5) phase-transitions in metabolic systems; 6) effects of cell growth and division; and 7) mono- and bistable bimodal switches.

Therapeutic perspectives of epigenetically active nutrients

PubMed Central

Remely, M; Lovrecic, L; de la Garza, A L; Migliore, L; Peterlin, B; Milagro, F I; Martinez, A J; Haslberger, A G

2015-01-01

Many nutrients are known for a wide range of activities in prevention and alleviation of various diseases. Recently, their potential role in regulating human health through effects on epigenetics has become evident, although specific mechanisms are still unclear. Thus, nutriepigenetics/nutriepigenomics has emerged as a new and promising field in current epigenetics research in the past few years. In particular, polyphenols, as part of the central dynamic interaction between the genome and the environment with specificity at physiological concentrations, are well known to affect mechanisms underlying human health. This review summarizes the effects of dietary compounds on epigenetic mechanisms in the regulation of gene expression including expression of enzymes and other molecules responsible for drug absorption, distribution, metabolism and excretion in cancer, metabolic syndrome, neurodegenerative disorders and hormonal dysfunction. PMID:25046997

Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: potential roles in GABAergic interneuron pathology.

PubMed

Schubert, Klaus Oliver; Föcking, Melanie; Cotter, David R

2015-09-01

Neuropathological changes of the hippocampus have been associated with psychotic disorders such as schizophrenia and bipolar disorder. Recent work has particularly implicated hippocampal GABAergic interneurons in the pathophysiology of these diseases. However, the molecular mechanisms underlying structural and cellular hippocampal pathology remain poorly understood. We used data from comprehensive difference-in-gel electrophoresis (2-D DIGE) investigations of postmortem human hippocampus of people with schizophrenia and bipolar disorder, covering the acidic (isoelectric point (pI) between pH4 and 7) and, separately, the basic (pI between pH6 and 11) sub-proteome, for Ingenuity Pathway Analysis (IPA) of implicated protein networks and pathways. Comparing disease and control cases, we identified 58 unique differentially expressed proteins in schizophrenia, and 70 differentially expressed proteins in bipolar disorder, using mass spectrometry. IPA implicated, most prominently, 14-3-3 and aryl hydrocarbon receptor signaling in schizophrenia, and gluconeogenesis/glycolysis in bipolar disorder. Both disorders were characterized by alterations of proteins involved in the oxidative stress response, mitochondrial function, and protein-endocytosis, -trafficking, -degradation, and -ubiquitination. These findings are interpreted with a focus on GABAergic interneuron pathology in the hippocampus. Copyright © 2015 Elsevier B.V. All rights reserved.

Atrial remodeling and metabolic dysfunction in idiopathic isolated fibrotic atrial cardiomyopathy.

PubMed

Cui, Chang; Jiang, Xiaohong; Ju, Weizhu; Wang, Jiaxian; Wang, Daowu; Sun, Zheng; Chen, Minglong

2018-08-15

Idiopathic isolated fibrotic atrial cardiomyopathy (IIF-ACM) is a novel subtype of cardiomyopathy characterized by atrial fibrosis that does not involve the ventricular myocardium and is associated with significant atrial tachyarrhythmia. The mechanisms underlying its pathogenesis are unknown. Atrium samples were obtained from 3 patients with IIF-ACM via surgical intervention. Control samples were consisted of 3 atrium biopsies from patients with congenital heart disease and normal sinus rhythm, matched for gender, age and basic clinical characteristics. Comparative histology, immunofluorescence staining, electron microscopy and proteomics analyses were carried out to explore the unique pathogenesis of IIF-ACM. IIF-ACM atria displayed disordered myofibrils, profound fibrosis and mitochondrial damages compared to the control atria. Proteomics profiling identified metabolic pathways as the most profound changes in IIF-ACM. Our study suggested that metabolic changes in the atrial myocardium caused mitochondrial oxidative stress and potential cell damage, which further led to atrial fibrosis and myofibril disorganization, the characteristic phenotype of IIF-ACM. Copyright © 2018 Elsevier B.V. All rights reserved.

Anesthetic Management of a Child With Unspecified Mitochondrial Disease in an Outpatient Dental Setting.

PubMed

Gordon, Taylor R; Montandon, Richard J

2017-01-01

Mitochondrial disease (MD) represents a category of metabolic disorders with a wide range of symptoms across a variety of organ systems. It occurs with an incidence of greater than 1:5000 and can be difficult to specifically diagnose because of the variety of clinical presentations and multiple genomic origins. Although phenotypically variable, MD symptoms often include hypotonia, cardiac defects, dysautonomia, and metabolic dysfunction. Mitochondrial disease presents a unique challenge in terms of anesthetic management, as many anesthetic drugs suppress mitochondrial function. Additional considerations may need to be made in order to evaluate the patient's metabolic compensation prior to surgery. This article presents an in-depth discussion of a case involving a nearly 10-year-old boy with a history of an unspecified form of MD, who presented for endodontic treatment of tooth No. 30 under deep sedation. The article also provides a thorough review of the current literature surrounding the anesthetic management of patients with MD.

The Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus Pandemic: Part I. Increased Cardiovascular Disease Risk and the Importance of Atherogenic Dyslipidemia in Persons With the Metabolic Syndrome and Type 2 Diabetes Mellitus

PubMed Central

Ginsberg, Henry N.; MacCallum, Paul R.

2010-01-01

Both the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) confer an increased risk of coronary heart disease and cardiovascular disease (CVD). As MS and T2DM become more prevalent, there will be an associated rise in the number of individuals with or at risk for CVD and its related disorders. One major underlying cause of CVD in patients with MS or T2DM is a characteristic form of atherogenic dyslipidemia. This article reviews the evidence that demonstrates that individuals with MS or T2DM are at increased risk for CVD and highlights atherogenic dyslipidemia as an important risk factor for the development of CVD in these individuals. In an accompanying article, current pharmacotherapies available for the management of atherogenic dyslipidemia in individuals with MS or T2DM are discussed. PMID:19614799

[Metabolic bone disease osteomalacia].

PubMed

Reuss-Borst, M A

2014-05-01

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

Neuronal Calcium Signaling in Metabolic Regulation and Adaptation to Nutrient Stress.

PubMed

Jayakumar, Siddharth; Hasan, Gaiti

2018-01-01

All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development. Here we review the role of a newly identified set of integrative interneurons and the role of intracellular calcium signaling within these neurons, in regulating nutrient sensing under conditions of nutrient stress. A comparison of the identified Drosophila circuit and cellular mechanisms employed in this circuit, with vertebrate systems, suggests that the identified cell signaling mechanisms may be conserved for neural circuit function related to nutrient sensing by central neurons. The ideas proposed are potentially relevant for understanding the molecular basis of metabolic disorders, because these are frequently linked to nutritional stress.

Decoding telomere protein Rap1: Its telomeric and nontelomeric functions and potential implications in diabetic cardiomyopathy.

PubMed

Cai, Yin; Kandula, Vidya; Kosuru, Ramoji; Ye, Xiaodong; Irwin, Michael G; Xia, Zhengyuan

2017-10-02

Mammalian Rap1, the most conserved telomere-interacting protein, beyond its role within nucleus for the maintenance of telomeric functions, is also well known for its pleiotropic functions in various physiological and pathological conditions associated with metabolism, inflammation and oxidative stress. For all these, nowadays Rap1 is the subject of critical investigations aimed to unveil its molecular signaling pathways and to scrutinize the applicability of its modulation as a promising therapeutic strategy with clinical relevance. However, the underlying intimate mechanisms of Rap1 are not extensively studied, but any modulation of this protein level has been associated with pathologies like inflammation, oxidative stress and deregulated metabolism. This is considerably important in light of the recent discovery of Rap1 modulation in diseases like cancer and cardiac metabolic disorders. In this review, we focus on both the telomeric and nontelomeric functions of Rap1 and its modulation in various health risks, especially on the heart.

Association between Magnesium Disorders and Hypocalcemia following Thyroidectomy.

PubMed

Nellis, Jason C; Tufano, Ralph P; Gourin, Christine G

2016-09-01

To identify factors associated with postoperative hypocalcemia after thyroid surgery and to understand the relationship among hypocalcemia, length of hospitalization, and costs of care. Retrospective database analysis. Discharge data from the Nationwide Inpatient Sample for 620,744 patients who underwent thyroid surgery from 2001 to 2010 were analyzed through cross-tabulations and multivariate regression modeling. Hypocalcemia, length of stay, and costs were examined as dependent variables. Secondary independent variables included magnesium and phosphate metabolism disorders, vitamin D deficiency, menopause, sex, extent of surgery, malignancy, and surgeon volume. Hypocalcemia was reported in 6% of patients and was significantly more common for the following variables: women, age <65 years, patients from the Northeast, total thyroidectomy ± neck dissection patients, low-volume surgical care, malignancy, recurrent laryngeal nerve injury, and patients with disorders of magnesium or phosphate metabolism (P < .001). Magnesium and phosphate disorders were present in <1% of patients. Magnesium disorders were significantly more likely for patients with hypocalcemia (7%; P < .001), and hypocalcemia was present in 52% of patients with magnesium disorders (P < .001). On multiple logistic regression analysis, the odds of hypocalcemia were greatest for patients with magnesium disorders (odds ratio, 12.71; 95% confidence interval, 8.59-18.82). This relationship was not attenuated by high-volume surgical care. Hypocalcemia and magnesium disorders were both associated with increased length of stay and costs, with a greater effect for magnesium disorders than for hypocalcemia (P < .001). Disorders of magnesium metabolism are an independent risk factor for postthyroidectomy hypocalcemia and are associated with significantly increased costs and length of stay. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Cortisol dysregulation in obesity-related metabolic disorders

PubMed Central

Baudrand, Rene; Vaidya, Anand

2015-01-01

Purpose of review The understanding of how adrenal function is challenged by the interplay of our genetic and environmental milieu has highlighted the importance of inappropriate cortisol regulation in cardiometabolic disorders. Increased adipose tissue in obesity is associated with hypothalamic-pituitary-adrenal axis over-activation, increased cortisol production at the local tissue level, and probably higher mineralocorticoid receptor activation in certain tissues. Recent findings Due to the clinical resemblance of obesity-related metabolic disorders with the Cushing syndrome, new studies have investigated the intracellular regulation and metabolism of cortisol, new measurements in scalp hair as a tool for long-term exposure and the cortisol-mineralocorticoid receptor pathway. Thus, current and future pharmacological interventions in obesity may include specific inhibition of steroidogenic and regulatory enzymes as well as antagonists of the mineralocorticoid and glucocorticoid receptors. Summary This review highlights recent investigations focusing on the role of dysregulated cortisol physiology in obesity as a potential modifiable mechanism in the pathogenesis of obesity related cardiometabolic disorders. PMID:25871955

Interplay between cancer cell cycle and metabolism: Challenges, targets and therapeutic opportunities.

PubMed

Roy, Debmalya; Sheng, Gao Ying; Herve, Semukunzi; Carvalho, Evandro; Mahanty, Arpan; Yuan, Shengtao; Sun, Li

2017-05-01

A growing interest has emerged in the field of studying the cross-talk between cancer cell cycle and metabolism. In this review, we aimed to present how metabolism and cell cycle are correlated and how cancer cells get energy to drive cell cycle. Cell proliferation and cell death largely depend on the metabolic activity of the cell. Cell cycle proteins, e.g. cyclin D, cyclin dependent kinase (CDK), some pro-apoptotic and anti-apoptotic proteins, and P53 have been shown to be regulated by metabolic crosstalk. Dysregulation of this cross-talk between metabolism and cell cycle leads to degenerative disorder(s) and cancer. It is not fully understood the actual reason of aberration between metabolism and cell cycle, but it is a hallmark of cancer research. Herein, we discussed the role of some regulatory molecules relative of cell cycle and metabolism and highlight how they control the function of each other. We also pointed out, current therapeutic opportunities and some additional crucial therapeutic targets on these fields that could be a breakthrough in cancer research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Overactive muscles: it can be more serious than common myalgia or cramp].

PubMed

Molenaar, Joery P F; Snoeck, Marc M J; Voermans, Nicol C; van Engelen, Baziel G M

2016-01-01

Positive muscle phenomena are due to muscle overactivity. Examples are cramp, myalgia, and stiffness. These manifestations have mostly acquired causes, e.g. side-effects of medication, metabolic disorders, vitamin deficiency, excessive caffeine intake or neurogenic disorders. We report on three patients with various positive muscle phenomena, to illustrate the clinical signs that indicate an underlying myopathy. Patient A, a 56-year-old man, was diagnosed with muscle cramp in the context of excessive coffee use and previous lumbosacral radiculopathy. Patient B, a 71-year-old man, was shown to have RYR1-related myopathy. Patient C, a 42-year-old man, suffered from Brody myopathy. We propose for clinicians to look out for a number of 'red flags' that can point to an underlying myopathy, and call for referral to neurology if indicated. Red flags include second wind phenomenon, familial occurrence of similar complaints, marked muscle stiffness, myotonia, muscle weakness, muscle hypertrophy, and myoglobinuria. Establishing a correct diagnosis is important for proper treatment. Certain myopathies call for cardiac or respiratory screening.

Disordered glycometabolism involved in pathogenesis of Kashin–Beck disease, an endemic osteoarthritis in China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Cuiyan, E-mail: xj.cy.69@stu.xjtu.edu.cn; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education; Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi'an, Shaanxi 710061

Kashin–Beck disease (KBD) is a chronic endemic osteoarthritis in China. Previous studies have suggested a role of metabolic dysfunction in causation of this disease. In this investigation, the metabolomics approach and cell experiments were used to discover the metabolic changes and their effects on KBD chondrocytes. Nuclear magnetic resonance ({sup 1}H NMR) spectroscopy was used to examine serum samples from both the KBD patients and normal controls. The pattern recognition multivariate analysis (OSC–PLS) and quantitative analysis (QMTLS iterator) revealed altered glycometabolism in KBD, with increased glucose and decreased lactate and citrate levels. IPA biological analysis showed the centric location ofmore » glucose in the metabolic network. Massive glycogen deposits in chondrocytes and increased uptake of glucose by chondrocytes further confirmed disordered glycometabolism in KBD. An in vitro study showed the effects of disordered glycometabolism in chondrocytes. When chondrocytes were treated with high glucose, expression of type II collagen and aggrecan were decreased, while TNF-α expression, the level of cellular reactive oxygen species and cell apoptosis rates all were increased. Therefore, our results demonstrated that disordered glycometabolism in patients with KBD was linked to the damage of chondrocytes. This may provide a new basis for understanding the pathogenesis of KBD. - Highlights: • Disordered glycometabolism in KBD was demonstrated by combining serum metabolomics and chondrocyte studies. • Glucose and TNF-α were key molecules linked to altered metabolism and inflammation in the pathophysiology of KBD. • The glycometabolism disorder was linked to expression of type II collagen and aggrecan, ROS and apoptosis of KBD chondrocytes.« less

Contribution of Inhibitor of DNA Binding/Differentiation-3 and Endocrine Disrupting Chemicals to Pathophysiological Aspects of Chronic Disease

PubMed Central

2017-01-01

The overwhelming increase in the global incidence of obesity and its associated complications such as insulin resistance, atherosclerosis, pulmonary disease, and degenerative disorders including dementia constitutes a serious public health problem. The Inhibitor of DNA Binding/Differentiation-3 (ID3), a member of the ID family of transcriptional regulators, has been shown to play a role in adipogenesis and therefore ID3 may influence obesity and metabolic health in response to environmental factors. This review will highlight the current understanding of how ID3 may contribute to complex chronic diseases via metabolic perturbations. Based on the increasing number of reports that suggest chronic exposure to and accumulation of endocrine disrupting chemicals (EDCs) within the human body are associated with metabolic disorders, we will also consider the impact of these chemicals on ID3. Improved understanding of the ID3 pathways by which exposure to EDCs can potentiate complex chronic diseases in populations with metabolic disorders (obesity, metabolic syndrome, and glucose intolerance) will likely provide useful knowledge in the prevention and control of complex chronic diseases associated with exposure to environmental pollutants. PMID:28785583

The mRNA expression levels of uncoupling proteins 1 and 2 in mononuclear cells from patients with metabolic disorders: obesity and type 2 diabetes mellitus.

PubMed

Margaryan, Sona; Witkowicz, Agata; Partyka, Anna; Yepiskoposyan, Levon; Manukyan, Gayane; Karabon, Lidia

2017-10-19

Type 2 diabetes mellitus (T2DM) and obesity are metabolic disorders whose major hallmark is insulin resistance. Impaired mitochondrial activity, such as reduced ratio of energy production to respiration, has been implicated in the development of insulin resistance. Uncoupling proteins (UCPs) are proton carriers, expressed in the mitochondrial inner membrane, that uncouple oxygen consumption by the respiratory chain from ATP synthesis. The aim of the study was to determine transcriptional levels of UCP1 and UCP2 in peripheral blood mononuclear cells (PBMCs) from patients with metabolic disorders: T2DM, obesity and from healthy individuals. The mRNA levels of UCP1, UCP2 were determined by Real-Time PCR method using Applied Biosystems assays. The UCP1 mRNA expression level was not detectable in the majority of studied samples, while very low expression was found in PBMCs from 3 obese persons. UCP2 mRNA expression level was detectable in all samples. The median mRNA expression of UCP2 was lower in all patients with metabolic disorders as compared to the controls (0.20+0.14 vs. 0.010+0.009, p=0.05). When compared separately, the differences of medians UCP2 mRNA expression level between the obese individuals and the controls as well as between the T2DM patients and the controls did not reach statistical significance. Decreased UCP2 gene expression in mononuclear cells from obese and diabetic patients might contribute to the immunological abnormalities in these metabolic disorders and suggests its role as a candidate gene in future studies of obesity and diabetes.

Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells

PubMed Central

Sahoo, Swagatika; Thiele, Ines

2013-01-01

Small intestinal epithelial cells (sIECs) have a significant share in whole body metabolism as they perform enzymatic digestion and absorption of nutrients. Furthermore, the diet plays a key role in a number of complex diseases including obesity and diabetes. The impact of diet and altered genetic backgrounds on human metabolism may be studied by using computational modeling. A metabolic reconstruction of human sIECs was manually assembled using the literature. The resulting sIEC model was subjected to two different diets to obtain condition-specific metabolic models. Fifty defined metabolic tasks evaluated the functionalities of these models, along with the respective secretion profiles, which distinguished between impacts of different dietary regimes. Under the average American diet, the sIEC model resulted in higher secretion flux for metabolites implicated in metabolic syndrome. In addition, enzymopathies were analyzed in the context of the sIEC metabolism. Computed results were compared with reported gastrointestinal (GI) pathologies and biochemical defects as well as with biomarker patterns used in their diagnosis. Based on our simulations, we propose that (i) sIEC metabolism is perturbed by numerous enzymopathies, which can be used to study cellular adaptive mechanisms specific for such disorders, and in the identification of novel co-morbidities, (ii) porphyrias are associated with both heme synthesis and degradation and (iii) disturbed intestinal gamma-aminobutyric acid synthesis may be linked to neurological manifestations of various enzymopathies. Taken together, the sIEC model represents a comprehensive, biochemically accurate platform for studying the function of sIEC and their role in whole body metabolism. PMID:23492669

Elevated Choline-Containing Compound Levels in Rapid Cycling Bipolar Disorder.

PubMed

Cao, Bo; Stanley, Jeffrey A; Passos, Ives Cavalcante; Mwangi, Benson; Selvaraj, Sudhakar; Zunta-Soares, Giovana B; Soares, Jair C

2017-10-01

Previous studies have found increased levels of choline-containing compounds (ie, glycerophosphocholine plus phosphocholine (GPC+PC)) in bipolar disorder using in vivo proton magnetic resonance spectroscopy ( 1 H MRS), especially in bipolar I disorder (BD-I). Increased levels of GPC+PC suggest alterations in the membrane phospholipids metabolism in bipolar disorder. Rapid cycling (RC) bipolar disorder is considered as a severe course of bipolar disorder, but it is unclear whether rapid cycling bipolar disorder is linked to highly altered membrane phospholipid metabolism. The purpose of this study was to investigate whether the regional extent of elevated GPC+PC were greater in BD-I patients with rapid cycling compared to BD-I patients without rapid cycling and healthy controls. Using a multi-voxel 1 H MRS approach at 3 Tesla with high spatial resolution and absolute quantification, GPC+PC levels from the anterior cingulate cortex (ACC), caudate and putamen of 16 RC BD-I, 34 non-RC BD-I and 44 healthy controls were assessed. We found significantly elevated GPC+PC levels in ACC, putamen and caudate of RC BD-I patients compared to healthy controls (P<0.005) and in ACC compared to non-RC BD-I patients (P<0.05). These results suggest greater alteration of membrane phospholipid metabolisms in rapid cycling BD-I compared to non-rapid-cycling BD-I.

Metabolic imaging in obesity: underlying mechanisms and consequences in the whole body.

PubMed

Iozzo, Patricia

2015-09-01

Obesity is a phenotype resulting from a series of causative factors with a variable risk of complications. Etiologic diversity requires personalized prevention and treatment. Imaging procedures offer the potential to investigate the interplay between organs and pathways underlying energy intake and consumption in an integrated manner, and may open the perspective to classify and treat obesity according to causative mechanisms. This review illustrates the contribution provided by imaging studies to the understanding of human obesity, starting with the regulation of food intake and intestinal metabolism, followed by the role of adipose tissue in storing, releasing, and utilizing substrates, including the interconversion of white and brown fat, and concluding with the examination of imaging risk indicators related to complications, including type 2 diabetes, liver pathologies, cardiac and kidney diseases, and sleep disorders. The imaging modalities include (1) positron emission tomography to quantify organ-specific perfusion and substrate metabolism; (2) computed tomography to assess tissue density as an indicator of fat content and browning/ whitening; (3) ultrasounds to examine liver steatosis, stiffness, and inflammation; and (4) magnetic resonance techniques to assess blood oxygenation levels in the brain, liver stiffness, and metabolite contents (triglycerides, fatty acids, glucose, phosphocreatine, ATP, and acetylcarnitine) in a variety of organs. © 2015 New York Academy of Sciences.

Cytochrome P450-2D6 Screening Among Elderly Using Antidepressants (CYSCE)

ClinicalTrials.gov

2017-08-15

Depression; Depressive Disorder; Poor Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Intermediate Metabolizer Due to Cytochrome P450 CYP2D6 Variant; Ultrarapid Metabolizer Due to Cytochrome P450 CYP2D6 Variant

Evaluation of dynamic thiol/disulphide homeostasis as a novel indicator of oxidative stress in maple syrup urine disease patients under treatment.

PubMed

Zubarioglu, Tanyel; Kiykim, Ertugrul; Cansever, Mehmet Serif; Neselioglu, Salim; Aktuglu-Zeybek, Cigdem; Erel, Ozcan

2017-02-01

Maple syrup urine disease (MSUD) is a metabolic disorder that is caused by deficiency of branched-chain α-keto acid dehydrogenase complex. Although accumulation of toxic metabolites is associated with neurotoxicity, mechanisms underlying brain damage remain unclear. Aim of this study is to evaluate thiol/disulphide homeostasis as a novel indicator of oxidative stress in MSUD patients under treatment. Twenty patients with MSUD and 20 healthy individuals were included in study. All patients were under regular follow-up and had a good metabolic control. Serum native thiol (-SH), total thiol (-SH + -S-S-), disulphide (-S-S) levels were measured in all subjects. Disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated from these values. Simultaneous blood sampling for plasma quantitative amino acid analysis was performed in both groups. Any significant difference was not observed in -SH, -SH + -S-S-, -S-S levels between two groups. In addition no increase of disulphide/native thiol and disulphide/total thiol ratios was detected in patient group. This study is the first study that evaluates dynamic thiol/disulphide homeostasis as an indicator of oxidative stress in MSUD patients. Among previous studies that were made to determine oxidative stress in treated MSUD patients, this study had the largest sample size also. In recent studies, it was claimed that oxidative stress could be responsible from neurotoxicity even in treated patients. Here, dynamic thiol/disulfide homeostasis status showed that providing good metabolic control in MSUD patients prevent oxidative stress. Under regular follow-up and good compliance with diet, additional antioxidant therapies would possibly not be necessary.

The gut microbiota and host health: a new clinical frontier.

PubMed

Marchesi, Julian R; Adams, David H; Fava, Francesca; Hermes, Gerben D A; Hirschfield, Gideon M; Hold, Georgina; Quraishi, Mohammed Nabil; Kinross, James; Smidt, Hauke; Tuohy, Kieran M; Thomas, Linda V; Zoetendal, Erwin G; Hart, Ailsa

2016-02-01

Over the last 10-15 years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Experience of microbiological screening of human hepatocytes for clinical transplantation.

PubMed

Lehec, Sharon C; Hughes, Robin D; Mitry, Ragai R; Graver, Michelle A; Verma, Anita; Wade, Jim J; Dhawan, Anil

2009-01-01

Hepatocyte transplantation is being used in patients with liver-based metabolic disorders and acute liver failure. Hepatocytes are isolated from unused donor liver tissue under GMP conditions. Cells must be free of microbiological contamination to be safe for human use. The experience of microbiological screening during 72 hepatocyte isolation procedures at one center is reported. Samples were taken at different stages of the process and tested using a blood culture bottle system and Gram stain. Bacterial contamination was detected in 37.5% of the UW organ preservative solutions used to transport the liver tissue to the Cell Isolation Unit. After tissue processing the contamination was reduced to 7% overall in the final hepatocyte product, irrespective of the presence of initial contamination of the transport solution. The most common organisms recovered were coagulase-negative staphylococci, a skin commensal. A total of 41 preparations of fresh or cryopreserved hepatocytes were used for cell transplantation in children with liver-based metabolic disorders without any evidence of sepsis due to infusion of hepatocytes. In conclusion, the incidence of bacterial contamination of the final product was low, confirming the suitability of the organs used, hepatocyte isolation procedure, and the environmental conditions of the clean room.

Theranostic Biomarkers for Schizophrenia

PubMed Central

Nikolac Perkovic, Matea; Nedic Erjavec, Gordana; Svob Strac, Dubravka; Uzun, Suzana; Kozumplik, Oliver; Pivac, Nela

2017-01-01

Schizophrenia is a highly heritable, chronic, severe, disabling neurodevelopmental brain disorder with a heterogeneous genetic and neurobiological background, which is still poorly understood. To allow better diagnostic procedures and therapeutic strategies in schizophrenia patients, use of easy accessible biomarkers is suggested. The most frequently used biomarkers in schizophrenia are those associated with the neuroimmune and neuroendocrine system, metabolism, different neurotransmitter systems and neurotrophic factors. However, there are still no validated and reliable biomarkers in clinical use for schizophrenia. This review will address potential biomarkers in schizophrenia. It will discuss biomarkers in schizophrenia and propose the use of specific blood-based panels that will include a set of markers associated with immune processes, metabolic disorders, and neuroendocrine/neurotrophin/neurotransmitter alterations. The combination of different markers, or complex multi-marker panels, might help in the discrimination of patients with different underlying pathologies and in the better classification of the more homogenous groups. Therefore, the development of the diagnostic, prognostic and theranostic biomarkers is an urgent and an unmet need in psychiatry, with the aim of improving diagnosis, therapy monitoring, prediction of treatment outcome and focus on the personal medicine approach in order to improve the quality of life in patients with schizophrenia and decrease health costs worldwide. PMID:28358316

Biochemical correlates of neuropsychiatric illness in maple syrup urine disease.

PubMed

Muelly, Emilie R; Moore, Gregory J; Bunce, Scott C; Mack, Julie; Bigler, Don C; Morton, D Holmes; Strauss, Kevin A

2013-04-01

Maple syrup urine disease (MSUD) is an inherited disorder of branched chain amino acid metabolism presenting with neonatal encephalopathy, episodic metabolic decompensation, and chronic amino acid imbalances. Dietary management enables survival and reduces risk of acute crises. Liver transplantation has emerged as an effective way to eliminate acute decompensation risk. Psychiatric illness is a reported MSUD complication, but has not been well characterized and remains poorly understood. We report the prevalence and characteristics of neuropsychiatric problems among 37 classical MSUD patients (ages 5-35 years, 26 on dietary therapy, 11 after liver transplantation) and explore their underlying mechanisms. Compared with 26 age-matched controls, MSUD patients were at higher risk for disorders of cognition, attention, and mood. Using quantitative proton magnetic resonance spectroscopy, we found lower brain glutamate, N-acetylaspartate (NAA), and creatine concentrations in MSUD patients, which correlated with specific neuropsychiatric outcomes. Asymptomatic neonatal course and stringent longitudinal biochemical control proved fundamental to optimizing long-term mental health. Neuropsychiatric morbidity and neurochemistry were similar among transplanted and nontransplanted MSUD patients. In conclusion, amino acid dysregulation results in aberrant neural networks with neurochemical deficiencies that persist after transplant and correlate with neuropsychiatric morbidities. These findings may provide insight into general mechanisms of psychiatric illness.

13C-tryptophan breath test detects increased catabolic turnover of tryptophan along the kynurenine pathway in patients with major depressive disorder

PubMed Central

Teraishi, Toshiya; Hori, Hiroaki; Sasayama, Daimei; Matsuo, Junko; Ogawa, Shintaro; Ota, Miho; Hattori, Kotaro; Kajiwara, Masahiro; Higuchi, Teruhiko; Kunugi, Hiroshi

2015-01-01

Altered tryptophan–kynurenine (KYN) metabolism has been implicated in major depressive disorder (MDD). The l-[1-13C]tryptophan breath test (13C-TBT) is a noninvasive, stable-isotope tracer method in which exhaled 13CO2 is attributable to tryptophan catabolism via the KYN pathway. We included 18 patients with MDD (DSM-IV) and 24 age- and sex-matched controls. 13C-tryptophan (150 mg) was orally administered and the 13CO2/12CO2 ratio in the breath was monitored for 180 min. The cumulative recovery rate during the 180-min test (CRR0–180; %), area under the Δ13CO2-time curve (AUC; %*min), and the maximal Δ13CO2 (Cmax; %) were significantly higher in patients with MDD than in the controls (p = 0.004, p = 0.008, and p = 0.002, respectively). Plasma tryptophan concentrations correlated negatively with Cmax in both the patients and controls (p = 0.020 and p = 0.034, respectively). Our results suggest that the 13C-TBT could be a novel biomarker for detecting a subgroup of MDD with increased tryptophan–KYN metabolism. PMID:26524975

Functional Mitochondria in Health and Disease.

PubMed

Herst, Patries M; Rowe, Matthew R; Carson, Georgia M; Berridge, Michael V

2017-01-01

The ability to rapidly adapt cellular bioenergetic capabilities to meet rapidly changing environmental conditions is mandatory for normal cellular function and for cancer progression. Any loss of this adaptive response has the potential to compromise cellular function and render the cell more susceptible to external stressors such as oxidative stress, radiation, chemotherapeutic drugs, and hypoxia. Mitochondria play a vital role in bioenergetic and biosynthetic pathways and can rapidly adjust to meet the metabolic needs of the cell. Increased demand is met by mitochondrial biogenesis and fusion of individual mitochondria into dynamic networks, whereas a decrease in demand results in the removal of superfluous mitochondria through fission and mitophagy. Effective communication between nucleus and mitochondria (mito-nuclear cross talk), involving the generation of different mitochondrial stress signals as well as the nuclear stress response pathways to deal with these stressors, maintains bioenergetic homeostasis under most conditions. However, when mitochondrial DNA (mtDNA) mutations accumulate and mito-nuclear cross talk falters, mitochondria fail to deliver critical functional outputs. Mutations in mtDNA have been implicated in neuromuscular and neurodegenerative mitochondriopathies and complex diseases such as diabetes, cardiovascular diseases, gastrointestinal disorders, skin disorders, aging, and cancer. In some cases, drastic measures such as acquisition of new mitochondria from donor cells occurs to ensure cell survival. This review starts with a brief discussion of the evolutionary origin of mitochondria and summarizes how mutations in mtDNA lead to mitochondriopathies and other degenerative diseases. Mito-nuclear cross talk, including various stress signals generated by mitochondria and corresponding stress response pathways activated by the nucleus are summarized. We also introduce and discuss a small family of recently discovered hormone-like mitopeptides that modulate body metabolism. Under conditions of severe mitochondrial stress, mitochondria have been shown to traffic between cells, replacing mitochondria in cells with damaged and malfunctional mtDNA. Understanding the processes involved in cellular bioenergetics and metabolic adaptation has the potential to generate new knowledge that will lead to improved treatment of many of the metabolic, degenerative, and age-related inflammatory diseases that characterize modern societies.

Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats.

PubMed

Ji, Chenlin; Dai, Yanyan; Jiang, Weiwei; Liu, Juan; Hou, Miao; Wang, Junle; Burén, Jonas; Li, Xiaonan

2014-11-01

Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet. Litters from Sprague-Dawley dams were culled to three (small litters) or ten (normal litters) pups and then weaned onto a standard or high-fat diet at postnatal day 21 to generate normal-litter, small-litter, normal-litter/high-fat, and small-litter/high-fat groups. At age 16 weeks, the small-litter and both high-fat groups showed obesity, dyslipidemia, and insulin resistance. Hepatic disorders appeared earlier in the small-litter/high-fat rats with greater liver mass gain and higher hepatic triglycerides and steatosis score versus normal-litter/high-fat rats. Hepatic acetyl-CoA carboxylase activity and mRNA expression were increased in small-litter rats and aggravated in small-litter/high-fat rats but not in normal-litter/high-fat rats. The high expression in small-litter/high-fat rats coincided with high sterol regulatory element-binding protein-1c mRNA and protein expression. However, mRNA expression of enzymes involved in hepatic fatty acid oxidation (carnitine palmitoyltransferase 1) and output (microsomal triglyceride transfer protein) was decreased under a high-fat diet regardless of litter size. In conclusion, overfeeding related to small-litter rearing during lactation contributes to the NAFLD phenotype when combined with a high-fat diet, possibly through up-regulated hepatic lipogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic alcoholism-mediated metabolic disorders in albino rat testes.

PubMed

Shayakhmetova, Ganna M; Bondarenko, Larysa B; Matvienko, Anatoliy V; Kovalenko, Valentina M

2014-09-01

There is good evidence for impairment of spermatogenesis and reductions in sperm counts and testosterone levels in chronic alcoholics. The mechanisms for these effects have not yet been studied in detail. The consequences of chronic alcohol consumption on the structure and/or metabolism of testis cell macromolecules require to be intensively investigated. The present work reports the effects of chronic alcoholism on contents of free amino acids, levels of cytochrome P450 3A2 (CYP3A2) mRNA expression and DNA fragmentation, as well as on contents of different cholesterol fractions and protein thiol groups in rat testes. Wistar albino male rats were divided into two groups: I - control (intact animals), II - chronic alcoholism (15% ethanol self-administration during 150 days). Following 150 days of alcohol consumption, testicular free amino acid content was found to be significantly changed as compared with control. The most profound changes were registered for contents of lysine (-53%) and methionine (+133%). The intensity of DNA fragmentation in alcohol-treated rat testes was considerably increased, on the contrary CYP3A2 mRNA expression in testis cells was inhibited, testicular contents of total and etherified cholesterol increased by 25% and 45% respectively, and protein SH-groups decreased by 13%. Multidirectional changes of the activities of testicular dehydrogenases were detected. We thus obtained complex assessment of chronic alcoholism effects in male gonads, affecting especially amino acid, protein, ATP and NADPH metabolism. Our results demonstrated profound changes in testes on the level of proteome and genome. We suggest that the revealed metabolic disorders can have negative implication on cellular regulation of spermatogenesis under long-term ethanol exposure.

Mitochondrial Citrate Transporter-dependent Metabolic Signature in the 22q11.2 Deletion Syndrome.

PubMed

Napoli, Eleonora; Tassone, Flora; Wong, Sarah; Angkustsiri, Kathleen; Simon, Tony J; Song, Gyu; Giulivi, Cecilia

2015-09-18

The congenital disorder 22q11.2 deletion syndrome (22qDS), characterized by a hemizygous deletion of 1.5-3 Mb on chromosome 22 at locus 11.2, is the most common microdeletion disorder (estimated prevalence of 1 in 4000) and the second risk factor for schizophrenia. Nine of ∼30 genes involved in 22qDS have the potential of disrupting mitochondrial metabolism (COMT, UFD1L, DGCR8, MRPL40, PRODH, SLC25A1, TXNRD2, T10, and ZDHHC8). Deficits in bioenergetics during early postnatal brain development could set the basis for a disrupted neuronal metabolism or synaptic signaling, partly explaining the higher incidence in developmental and behavioral deficits in these individuals. Here, we investigated whether mitochondrial outcomes and metabolites from 22qDS children segregated with the altered dosage of one or several of these mitochondrial genes contributing to 22qDS etiology and/or morbidity. Plasma metabolomics, lymphocytic mitochondrial outcomes, and epigenetics (histone H3 Lys-4 trimethylation and 5-methylcytosine) were evaluated in samples from 11 22qDS children and 13 age- and sex-matched neurotypically developing controls. Metabolite differences between 22qDS children and controls reflected a shift from oxidative phosphorylation to glycolysis (higher lactate/pyruvate ratios) accompanied by an increase in reductive carboxylation of α-ketoglutarate (increased concentrations of 2-hydroxyglutaric acid, cholesterol, and fatty acids). Altered metabolism in 22qDS reflected a critical role for the haploinsufficiency of the mitochondrial citrate transporter SLC25A1, further enhanced by HIF-1α, MYC, and metabolite controls. This comprehensive profiling served to clarify the biochemistry of this disease underlying its broad, complex phenotype. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis.

PubMed

Ivanovski, Ivan; Ješić, Miloš; Ivanovski, Ana; Garavelli, Livia; Ivanovski, Petar

2017-11-28

The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.

Toxicological assessment of drugs that affect the endocrine system in puberty-related disorders.

PubMed

Maranghi, Francesca; Tassinari, Roberta; Mantovani, Alberto

2013-10-01

Toxicologists must ensure that clinical risk-to-benefit analysis should be made both for genders and age groups, with any treatment. Puberty concerns physiological changes leading to organism's maturation. Pubertal growth disorders are increasing in last decades: besides causing physical and psychological distress, they may signal underlying endocrine-metabolic abnormalities with serious health consequences later on. Therapeutic approaches for some health conditions in childhood and adolescence are considered. The authors discuss how some diseases and treatments can impact pubertal growth. The authors look at particular immunological disorders such as asthma and how both the disease and treatment affects pubertal growth. They also discuss how the provision of available data can help to assess the dose-response of the drug, in these cases, and minimize the chance of side effects. The authors also discuss pediatric inflammatory bowel disease and how both the disease and treatment can mitigate the growth delay. Last, but not least, the authors discuss how the effects of the drugs used in the treatment of psychiatric disorders may accentuate endocrine issues in juvenile patients. Hyperprolactinemia induction by some antipsychotics is highlighted as an example. Appropriate risk-benefit analysis of drugs prescribed during childhood and adolescence and intended to be used in the long term is required. Furthermore, future treatment strategies and safer compounds development should be supported by the knowledge of mechanisms underlying adverse side effects in pubertal growth and development.

Metabolic phenotyping of an adoptive transfer mouse model of experimental colitis and impact of dietary fish oil intake.

PubMed

Martin, Francois-Pierre J; Lichti, Pia; Bosco, Nabil; Brahmbhatt, Viral; Oliveira, Manuel; Haller, Dirk; Benyacoub, Jalil

2015-04-03

Inflammatory bowel diseases are acute and chronic disabling inflammatory disorders with multiple complex etiologies that are not well-defined. Chronic intestinal inflammation has been linked to an energy-deficient state of gut epithelium with alterations in oxidative metabolism. Plasma-, urine-, stool-, and liver-specific metabonomic analyses are reported in a naïve T cell adoptive transfer (AT) experimental model of colitis, which evaluated the impact of long-chain n-3 polyunsaturated fatty acid (PUFA)-enriched diet. Metabolic profiles of AT animals and their controls under chow diet or fish oil supplementation were compared to describe the (i) consequences of inflammatory processes and (ii) the differential impact of n-3 fatty acids. Inflammation was associated with higher glycoprotein levels (related to acute-phase response) and remodeling of PUFAs. Low triglyceride levels and enhanced PUFA levels in the liver suggest activation of lipolytic pathways that could lead to the observed increase of phospholipids in the liver (including plasmalogens and sphingomyelins). In parallel, the increase in stool excretion of most amino acids may indicate a protein-losing enteropathy. Fecal content of glutamine was lower in AT mice, a feature exacerbated under fish oil intervention that may reflect a functional relationship between intestinal inflammatory status and glutamine metabolism. The decrease in Krebs cycle intermediates in urine (succinate, α-ketoglutarate) also suggests a reduction in the glutaminolytic pathway at a systemic level. Our data indicate that inflammatory status is related to this overall loss of energy homeostasis.

Reversible Microvascular Hyporeactivity to Acetylcholine During Diabetic Ketoacidosis.

PubMed

Joffre, Jérémie; Bourcier, Simon; Hariri, Geoffroy; Miailhe, Arnaud-Felix; Bigé, Naike; Dumas, Guillaume; Dubée, Vincent; Boelle, Pierre-Yves; Abdallah, Idriss; Baudel, Jean-Luc; Guidet, Bertrand; Maury, Eric; Ait-Oufella, Hafid

2018-05-18

Metabolic acidosis is commonly observed in critically ill patients. Experimental studies suggested that acidosis by itself could impair vascular function, but this has been poorly investigated in human. Prospective observational study. Medical ICU in a tertiary teaching hospital. To assess the relationship between metabolic acidosis severity and microvascular reactivity, we included adult diabetic patients admitted in ICU for ketoacidosis. Microvascular response to acetylcholine iontophoresis was measured at admission (baseline) and after correction of metabolic acidosis (24 hr). None. Thirty-nine patients with diabetic ketoacidosis were included (68% male), with a median age of 43 (31-57) years. At admission, microvascular reactivity negatively correlated with acidosis severity (R = -0.53; p < 0.001). Microvascular response was strongly depressed at pH less than 7.20 (area under the curve, 1,779 [740-3,079] vs 12,944 [4,874-21,596] at pH > 7.20; p < 0.0001). In addition, acidosis severity was significantly correlated with capillary refill time (R = 0.50; p = 0.02). At H24, after rehydration and insulin infusion, clinical and biological disorders were fully corrected. After acidosis correction, microvascular reactivity increased more in patients with severe baseline acidosis (pH < 7.20) than in those with mild baseline acidosis (area under the curve, +453% [213%-1,470%] vs +121% [79%-312%]; p < 0.01). We identified an alteration of microvascular reactivity during metabolic acidosis in critically ill patients with diabetic ketoacidosis. Microvascular hyporeactivity recovered after acidosis correction.

[Consensus statement on metabolic disorders and cardiovascular risks in patients with human immunodeficiency virus].

PubMed

Polo Rodríguez, Rosa; Galindo Puerto, María José; Dueñas, Carlos; Gómez Candela, Carmen; Estrada, Vicente; Villar, Noemí G P; Locutura, Jaime; Mariño, Ana; Pascua, Javier; Palacios, Rosario; von Wichmman, Miguel Ángel; Álvarez, Julia; Asensi, Victor; Lopez Aldeguer, José; Lozano, Fernando; Negredo, Eugenia; Ortega, Enrique; Pedrol, Enric; Gutiérrez, Félix; Sanz Sanz, Jesús; Martínez Chamorro, Esteban

2015-01-01

This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients. This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system. A healthy lifestyle is recommended, no smoking and at least 30min of aerobic exercise daily. In diabetic patients the same treatment as non-HIV infected patients is recommended. HIV patients with dyslipidemia should be considered as high CVR, thus its therapeutic objective is an LDL less than 100mg/dL. The antihypertensive of ACE inhibitors and ARAII families are better tolerated and have a lower risk of interactions. In HIV-patients with diabetes or metabolic syndrome and elevated transaminases with no defined etiology, the recommended is to rule out a hepatic steatosis Recommendations for action in hormone alterations are also updated. These new guidelines update previous recommendations regarding all those metabolic disorders involved in CVR. Hormone changes and their management and the impact of metabolic disorders on the liver are also included. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

PubMed Central

Heisler, Jillian M.; O’Connor, Jason C.

2015-01-01

Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

The Effects of an Exercise Program on Anxiety Levels and Metabolic Functions in Patients With Anxiety Disorders.

PubMed

Ma, Wei-Fen; Wu, Po-Lun; Su, Chia-Hsien; Yang, Tzu-Ching

2017-05-01

The purpose of this study was to evaluate the effects of a home-based (HB) exercise program on anxiety levels and metabolic functions in patients with anxiety disorders in Taiwan. Purposive sampling was used to recruit 86 participants for this randomized, experimental study. Participants were asked to complete a pretest before the 3-month exercise program, a posttest at 1 week, and a follow-up test at 3 months after the exercise program. Study measures included four Self-Report Scales and biophysical assessments to collect and assess personal data, lifestyle behaviors, anxiety levels, and metabolic control functions. Of the 86 study participants, 83 completed the posttest and the 3-month follow-up test, including 41 in the experimental group and 42 in the control group. Participants in the experimental group showed significant improvements in body mass index, high-density lipoprotein cholesterol levels, and the level of moderate exercise after the program relative to the control group, as analyzed by generalized estimating equations mixed-model repeated measures. State and trait anxiety levels were also significantly improved from pretest to follow-up test in the experimental group. Finally, the prevalence of metabolic syndrome declined for participants in the experimental group. The HB exercise program produced positive effects on the metabolic indicators and anxiety levels of Taiwanese adults with anxiety disorders. Health providers should consider using similar HB exercise programs to help improve the mental and physical health of patients with anxiety disorders in their communities.

High carbohydrate intake from starchy foods is positively associated with metabolic disorders: a Cohort Study from a Chinese population

PubMed Central

Feng, Rennan; Du, Shanshan; Chen, Yang; Zheng, Sining; Zhang, Wei; Na, Guanqiong; Li, Ying; Sun, Changhao

2015-01-01

Starchy foods are the main sources of carbohydrates; however, there is limited information on their metabolic impact. Therefore, we assessed the association between carbohydrates from starchy foods (Carb-S) intakes and the metabolic disorders of metabolic syndrome (MetS) and hyperlipidemia. In this study, 4,154 participants from Northern China were followed up for 4.2 years. Carb-S included rice, refined wheat, tubers, and their products. Multivariable regression models were used to calculate risk ratios (RRs) for MetS and hyperlipidemia from Carb-S, total carbohydrates, and carbohydrates from other food sources (Carb-O). Receiver operating characteristic analysis was used to determine a Carb-S cut-off value. High total carbohydrate intake was associated with increased risks of MetS (RR: 2.24, 95% CI: 1.00–5.03) and hyperlipidemia (RR: 3.05, 95% CI: 1.25–7.45), compared with the first quartile. High Carb-S intake (fourth quartile) was significantly associated with MetS (RR: 1.48, 95% CI: 1.01–2.69) and hyperlipidemia (RR: 1.73, 95% CI: 1.05–3.35). No associations with Carb-O were observed. Visceral adiposity, triglyceride levels, and high-density lipoprotein cholesterol significantly contributed to the metabolic disorders. The Carb-S cut-off value was 220 g. Both high total carbohydrate and Carb-S intakes were associated with hyperlipidemia and MetS; Carb-S appears to contribute more to these disorders. PMID:26581652

In vivo exposures to particulate matter collected from Saudi Arabia or nickel chloride display similar dysregulation of metabolic syndrome genes

PubMed Central

Brocato, Jason; Hernandez, Michelle; Laulicht, Freda; Sun, Hong; Shamy, Magdy; Alghamdi, Mansour A.; Khoder, Mamdouh I.; Kluz, Thomas; Chen, Lung-Chi; Costa, Max

2016-01-01

Particulate matter (PM) exposures have been linked to mortality, low birth weights, hospital admissions, and diseases associated with metabolic syndrome, including diabetes mellitus, cardiovascular disease, and obesity. In a previous in vitro and in vivo study, data demonstrated that PM10µm collected from Jeddah, Saudi Arabia (PMSA) altered expression of genes involved in lipid and cholesterol metabolism, as well as many other genes associated with metabolic disorders. PMSA contains a relatively high concentration of nickel (Ni), known to be linked to several metabolic disorders. In order to evaluate if Ni and PM exposures induce similar gene expression profiles, mice were exposed to 100µg/50µl PMSA (PM-100), 50µg/50µl nickel chloride (Ni-50), or 100µg/50µl nickel chloride (Ni-100) twice a week for 4 weeks and hepatic gene expression changes determined. Ultimately, 55 of the same genes were altered in all 3 exposures. However, where the two Ni groups differed markedly was in the regulation (up or down) of these genes. Ni-100 and PM-100 groups displayed similar regulations, whereby 104 of the 107 genes were similarly modulated. Many of the 107 genes involved in metabolic syndrome and include ALDH4A1, BCO2, CYP1A, CYP2U, TOP2A. In addition, the top affected pathways such as fatty acid α-oxidation, and lipid and carbohydrate metabolism, are involved in metabolic diseases. Most notably, the top diseased outcome affected by these changes in gene expression was cardiovascular disease. Given these data, it appears that Ni and PMSA exposures display similar gene expression profiles, modulating the expression of genes involved in metabolic disorders. PMID:26692068

[THE OPTIMIZATION OF NUTRITION FUNCTION UNDER SYNDROME OF RESISTANCE TO INSULIN, DISORDER OF FATTY ACIDS' METABOLISM AND ABSORPTION OF GLUCOSE BY CELLS (A LECTURE)].

PubMed

Titov, V N

2016-01-01

The phylogenetic processes continue to proceed in Homo Sapiens. At the very early stages ofphylogenesis, the ancient Archaea that formed mitochondria under symbiotic interaction with later bacterial cells conjointly formed yet another system. In this system, there are no cells' absorption of glucose if it is possible to absorb fatty acids from intercellular medium in the form of unesterfied fatty acids or ketonic bodies--metabolites of fatty acids. This is caused by objectively existed conditions and subsequent availability of substrates at the stages ofphylogenesis: acetate, ketonic bodies, fatty acids and only later glucose. The phylogenetically late insulin used after billions years the same dependencies at formation of regulation ofmetabolism offatty acids and cells' absorption of glucose. In order that syndrome ofresistance ceased to exist as afoundation of metabolic pandemic Homo Sapiens has to understand the following. After successful function ofArchaea+bacterial cells and considered by biology action of insulin for the third time in phylogenesis and using biological function of intelligence the content ofphylogenetically earlier palmitic saturated fatty acid infood can't to exceed possibilities of phylogenetically late lipoproteins to transfer it in intercellular medium and blood and cells to absorb it. It is supposed that at early stages of phylogenesis biological function of intelligence is primarily formed to bring into line "unconformities" of regulation of metabolism against the background of seeming relative biological "perfection". These unconformities were subsequently and separately formed at the level of cells in paracrin regulated cenosises of cells and organs and at the level of organism. The prevention of resistance to insulin basically requires biological function of intelligence, principle of self-restraint, bringing into line multiple desires of Homo Sapiens with much less extensive biological possibilities. The "unconformities" of regulation of metabolism in vivo are etiological factors of all metabolic pandemics including atherosclerosis, metabolic arterial hypertension, obesity and metabolic syndrome Tertiannondatum.

Interactions of Circadian Rhythmicity, Stress and Orexigenic Neuropeptide Systems: Implications for Food Intake Control.

PubMed

Blasiak, Anna; Gundlach, Andrew L; Hess, Grzegorz; Lewandowski, Marian H

2017-01-01

Many physiological processes fluctuate throughout the day/night and daily fluctuations are observed in brain and peripheral levels of several hormones, neuropeptides and transmitters. In turn, mediators under the "control" of the "master biological clock" reciprocally influence its function. Dysregulation in the rhythmicity of hormone release as well as hormone receptor sensitivity and availability in different tissues, is a common risk-factor for multiple clinical conditions, including psychiatric and metabolic disorders. At the same time circadian rhythms remain in a strong, reciprocal interaction with the hypothalamic-pituitary-adrenal (HPA) axis. Recent findings point to a role of circadian disturbances and excessive stress in the development of obesity and related food consumption and metabolism abnormalities, which constitute a major health problem worldwide. Appetite, food intake and energy balance are under the influence of several brain neuropeptides, including the orexigenic agouti-related peptide, neuropeptide Y, orexin, melanin-concentrating hormone and relaxin-3. Importantly, orexigenic neuropeptide neurons remain under the control of the circadian timing system and are highly sensitive to various stressors, therefore the potential neuronal mechanisms through which disturbances in the daily rhythmicity and stress-related mediator levels contribute to food intake abnormalities rely on reciprocal interactions between these elements.

Should Metabolic Diseases Be Systematically Screened in Nonsyndromic Autism Spectrum Disorders?

PubMed Central

Schiff, Manuel; Benoist, Jean-François; Aïssaoui, Sofiane; Boepsflug-Tanguy, Odile; Mouren, Marie-Christine; de Baulny, Hélène Ogier; Delorme, Richard

2011-01-01

Background In the investigation of autism spectrum disorders (ASD), a genetic cause is found in approximately 10–20%. Among these cases, the prevalence of the rare inherited metabolic disorders (IMD) is unknown and poorly evaluated. An IMD responsible for ASD is usually identified by the associated clinical phenotype such as dysmorphic features, ataxia, microcephaly, epilepsy, and severe intellectual disability (ID). In rare cases, however, ASD may be considered as nonsyndromic at the onset of a related IMD. Objectives To evaluate the utility of routine metabolic investigations in nonsyndromic ASD. Patients and Methods We retrospectively analyzed the results of a metabolic workup (urinary mucopolysaccharides, urinary purines and pyrimidines, urinary creatine and guanidinoacetate, urinary organic acids, plasma and urinary amino acids) routinely performed in 274 nonsyndromic ASD children. Results The metabolic parameters were in the normal range for all but 2 patients: one with unspecific creatine urinary excretion and the other with persistent 3-methylglutaconic aciduria. Conclusions These data provide the largest ever reported cohort of ASD patients for whom a systematic metabolic workup has been performed; they suggest that such a routine metabolic screening does not contribute to the causative diagnosis of nonsyndromic ASD. They also emphasize that the prevalence of screened IMD in nonsyndromic ASD is probably not higher than in the general population (<0.5%). A careful clinical evaluation is probably more reasonable and of better medical practice than a costly systematic workup. PMID:21760924