scholarly journals The Accumulation and Molecular Effects of Trimethylamine N-Oxide on Metabolic Tissues: It’s Not All Bad

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2873
Author(s):  
Emily S. Krueger ◽  
Trevor S. Lloyd ◽  
Jeffery S. Tessem
Keyword(s):  
Metabolic Disease ◽  
Vascular Tissue ◽  
Metabolic Diseases ◽  
Elevated Serum ◽  
Serum Levels ◽  
Increased Risk ◽  
Cognitive Diseases ◽  
Molecular Effects ◽  
Glucose Management ◽  
Dietary Choline

Since elevated serum levels of trimethylamine N-oxide (TMAO) were first associated with increased risk of cardiovascular disease (CVD), TMAO research among chronic diseases has grown exponentially. We now know that serum TMAO accumulation begins with dietary choline metabolism across the microbiome-liver-kidney axis, which is typically dysregulated during pathogenesis. While CVD research links TMAO to atherosclerotic mechanisms in vascular tissue, its molecular effects on metabolic tissues are unclear. Here we report the current standing of TMAO research in metabolic disease contexts across relevant tissues including the liver, kidney, brain, adipose, and muscle. Since poor blood glucose management is a hallmark of metabolic diseases, we also explore the variable TMAO effects on insulin resistance and insulin production. Among metabolic tissues, hepatic TMAO research is the most common, whereas its effects on other tissues including the insulin producing pancreatic β-cells are largely unexplored. Studies on diseases including obesity, diabetes, liver diseases, chronic kidney disease, and cognitive diseases reveal that TMAO effects are unique under pathologic conditions compared to healthy controls. We conclude that molecular TMAO effects are highly context-dependent and call for further research to clarify the deleterious and beneficial molecular effects observed in metabolic disease research.

scholarly journals Elevated Serum Levels of Cysteine and Tyrosine: Early Biomarkers in Asymptomatic Adults at Increased Risk of Developing Metabolic Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Nina Mohorko ◽  
Ana Petelin ◽  
Mihaela Jurdana ◽  
Gianni Biolo ◽  
Zala Jenko-Pražnikar
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Amino Acids ◽  
Metabolic Diseases ◽  
Elevated Serum ◽  
Serum Levels ◽  
Metabolic Complications ◽  
Markers Of Inflammation ◽  
Increased Risk

As there is effective intervention for delaying or preventing metabolic diseases, which are often present for years before becoming clinically apparent, novel biomarkers that would mark metabolic complications before the onset of metabolic disease should be identified. We investigated the role of fasting serum amino acids and their associations with inflammatory markers, adipokines, and metabolic syndrome (MetS) components in subjects prior to the onset of insulin resistance (IR). Anthropometric measurements, food records, adipokines, biochemical markers, and serum levels of amino acids were determined in 96 asymptomatic subjects aged 25–49 years divided into three groups according to the number of MetS components present. Cysteine and tyrosine were significantly higher already in group with one component of MetS present compared to subjects without MetS components. Serum amino acid levels correlated with markers of inflammation and adipokines. Alanine and glycine explained 10% of insulin resistance variability. The role of tyrosine and cysteine, that were higher already with 1 component of MetS present, should be further investigated as they might point to future insulin disturbances.

scholarly journals Serum Levels of Asprosin, a Novel Adipokine, Are Significantly Lowered in Patients with Acromegaly

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiaoan Ke ◽  
Lian Duan ◽  
Fengying Gong ◽  
Yuelun Zhang ◽  
Kan Deng ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Metabolic Diseases ◽  
Influencing Factor ◽  
Clinical Information ◽  
Serum Levels ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Retrospective Case ◽  
Cell Adenoma ◽  
Increased Risk

Background. Asprosin is a novel identified adipokine secreted mainly by white adipose tissue, which is elevated in metabolic diseases such as diabetes and obesity. Acromegaly is a syndrome caused by pituitary growth hormone (GH) cell adenoma with excessive GH secretion. Serum adipocytokines levels may be involved in abnormal glycolipid metabolism in acromegaly patients. Objectives. To investigate serum asprosin levels in acromegaly patients and its correlation with high GH levels and glucolipid metabolic parameters. Methods. A retrospective case-control study was conducted and 68 acromegaly patients and 121 controls were included in this study. Clinical information and laboratory examinations were collected and serum asprosin levels were measured by commercial ELISA kits. Results. Serum asprosin levels in acromegaly patients were significantly lower than controls ( P < 0.001 ). Serum asprosin levels in patients with the course of acromegaly ≥5 years (compared with <5 years), high area under curve of growth hormone (GH-AUC) after 75 g oral glucose tolerance test (OGTT) (compared with low GH-AUC patients), and high IGF-1 SDS group (compared with low IGF-1 SDS group) were significantly reduced (all P < 0.05 ). Serum asprosin levels in acromegaly patients were negatively correlated with the course of acromegaly, IGF-1 SDS, nadir growth hormone value (GH-Nadir), and GH-AUC after OGTT. Multiple stepwise linear regression indicated that acromegaly was an independent influencing factor of serum asprosin levels. According to serum asprosin levels tertiles, the risk of acromegaly in the lowest group was 2.67 times higher than the highest group (OR ＝ 3.665, 95% CI 1.677 ∼ 8.007, P = 0.001 ), and the increased risk of the lowest group still existed after adjusting for gender, age, BMI, and TC (Model 2). Conclusions. Serum asprosin levels in acromegaly patients are lowered, which may be related to increased blood glucose and reduced body fat mass caused by long-term high GH levels exposure.

scholarly journals Analysis of serum levels of organochlorine pesticides and related factors in Parkinson’s disease

2020 ◽  
Author(s):  
Shaoqing Xu ◽  
Xiaodong Yang ◽  
Yiwei Qian ◽  
Dayong Wan ◽  
Fenghua Sun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Organochlorine Pesticides ◽  
Genetic Variants ◽  
Cell Model ◽  
Elevated Serum ◽  
Depression Scale ◽  
Serum Levels ◽  
Hamilton Depression Scale ◽  
Increased Risk

Abstract Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. Interactions between high pesticide levels and polymorphisms in rs11931074 and rs16940758 (α-HCH or β-HCH interacted with TT genotype in rs11931074 and δ-HCH interacted with TT genotype in rs16940758) were associated with the risk of PD. In cell model, α-HCH and propanil increased the level of reactive oxygen species and decreased the mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.

Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo

2017 ◽  
Vol 95 (4) ◽  
pp. 474-481 ◽  
Author(s):  
Rehab A. Karam ◽  
Haidy E. Zidan ◽  
Mohamed H. Khater
Keyword(s):  
Elevated Serum ◽  
Serum Levels ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Parameters ◽  
Increased Risk ◽  
Tnf Α ◽  
Ifn Γ

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality

2005 ◽  
Vol 43 (10) ◽  
Author(s):  
Rainer H. Böger ◽  
Renke Maas ◽  
Friedrich Schulze ◽  
Edzard Schwedhelm
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Asymmetric Dimethylarginine ◽  
Metabolic Diseases ◽  
Serum Levels ◽  
Major Adverse Cardiovascular Events ◽  
Blood Levels ◽  
Increased Risk ◽  
Vasoactive Mediator

AbstractThe endothelium plays a crucial role in the maintenance of vascular tone and structure by releasing the endothelium-derived vasoactive mediator, nitric oxide (NO). NO is formed in healthy vascular endothelium from the amino acid precursor L-arginine. Endothelial dysfunction is caused by various cardiovascular risk factors, metabolic diseases, and systemic or local inflammation. One mechanism that explains the occurrence of endothelial dysfunction is the presence of elevated blood levels of asymmetric dimethylarginine (ADMA) – an L-arginine analogue that inhibits NO formation and thereby can impair vascular function. Accumulating evidence from prospective clinical studies suggests that elevated plasma or serum levels of ADMA are associated with an increased risk of major adverse cardiovascular events. This article gives an updated overview of the currently available literature on ADMA and cardiovascular disease from prospective clinical trials. Recently, advances have been made in the development of analytical methods that are reliable and fast enough to allow determination of ADMA in clinical routine.

scholarly journals ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

1998 ◽  
Vol 40 (4) ◽  
pp. 219-224 ◽  
Author(s):  
Fernando Lopes GONÇALES Jr. ◽  
Raquel Silveira Bello STUCCHI ◽  
Priscila Maria Oliveira PAPAIORDANOU ◽  
Maria Helena Postal PAVAN ◽  
Neiva Sellan Lopes GONÇALES ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Blood Donors ◽  
Elevated Serum ◽  
Abdominal Ultrasound ◽  
Serum Levels ◽  
Gamma Glutamyl Transpeptidase ◽  
Period 2 ◽  
Increased Risk

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.

scholarly journals Interaction Between Genetic Variants and Serum Levels of Organochlorine Pesticides Contributes to Parkinson’s Disease

2020 ◽  
Author(s):  
Shaoqing Xu ◽  
Xiaodong Yang ◽  
Yiwei Qian ◽  
Dayong Wan ◽  
Fenghua Sun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Organochlorine Pesticides ◽  
Genetic Variants ◽  
Elevated Serum ◽  
Depression Scale ◽  
Serum Levels ◽  
Hamilton Depression Scale ◽  
Cross Sectional ◽  
Increased Risk

Abstract Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. The interaction between rs11931074 in α-synuclein (SNCA) and α-HCH or β-HCH, respectively, as well as rs16940758 in the microtubule-associated protein tau (MAPT) gene and δ-HCH were related to increased risk of PD. In addition, α-HCH and propanil enhanced the production of reactive oxygen species and decreased of mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.

scholarly journals Challenges in the Management of Atrial Fibrillation With Subclinical Hyperthyroidism

2022 ◽  
Vol 12 ◽  
Author(s):  
Baris Gencer ◽  
Anne R. Cappola ◽  
Nicolas Rodondi ◽  
Tinh-Hai Collet
Keyword(s):  
Atrial Fibrillation ◽  
Elevated Serum ◽  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Reference Ranges ◽  
Subclinical Hyperthyroidism ◽  
Older Individuals ◽  
Increased Risk ◽  
Patients At Risk ◽  
Novel Strategy

Subclinical thyroid disorders have a high prevalence among older individuals and women. Subclinical hypothyroidism is diagnosed by elevated serum levels of thyroid-stimulating hormone (TSH) with thyroxine levels within the reference range, and subclinical hyperthyroidism is diagnosed by low TSH in conjunction with thyroxine and triiodothyronine levels within reference ranges. Atrial fibrillation is the most commonly diagnosed cardiac arrhythmia and has been associated with an increased risk of mortality, heart failure, stroke, and depression. Mechanistic data from animal and human physiology studies as well as observational data in humans support an association of subclinical hyperthyroidism with atrial fibrillation. Guidelines recommend the measurement of TSH in the evaluation of new-onset atrial fibrillation. All patients with overt hyperthyroidism should be treated, and treatment of subclinical hyperthyroidism should be considered in patients older than 65 years with TSH &lt; 0.4 mlU/L, or in younger patients with TSH &lt; 0.1 mlU/L. Guidelines also recommend screening for AF in patients with known hyperthyroidism. Wearable devices that measure the heart electrical activity continuously may be a novel strategy to detect atrial fibrillation in patients at risk. In this review, we explore the interplay between thyroid hormones and atrial fibrillation, management controversies in subclinical hyperthyroidism, and potential strategies to improve the management of atrial fibrillation in patients with subclinical hyperthyroidism.

scholarly journals Amino Acid and Phospholipid Metabolism as an Indicator of Inflammation and Subtle Cardiomyopathy in Patients with Marfan Syndrome

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 805
Author(s):  
Lisa Bartenbach ◽  
Thomas Karall ◽  
Jakob Koch ◽  
Markus Andreas Keller ◽  
Herbert Oberacher ◽  
...  
Keyword(s):  
Amino Acid ◽  
Marfan Syndrome ◽  
Aortic Root ◽  
Myocardial Function ◽  
Elevated Serum ◽  
Serum Levels ◽  
Phospholipid Metabolism ◽  
Monitoring Tools ◽  
Increased Risk ◽  
History Of

Patients with Marfan syndrome (MFS) have an increased risk of aortic aneurysm formation, dissection and development of a subtle cardiomyopathy. We analyzed amino acid and lipid metabolic pathways in MFS patients, seeking biomarker patterns as potential monitoring tools of cardiovascular risk with deterioration of myocardial function. We assessed myocardial function in 24 adult MFS patients and compared traditional laboratory values and mass spectrometry-based amino acid, phospholipid and acylcarnitine metabolomes in patients with those in healthy controls. Analytes for which values differed between patients and controls were subjected to regression analysis. A high proportion of patients had signs of impaired diastolic function and elevated serum levels of NT-proBNP. Patients had lower serum levels of taurine, histidine and PCaeC42:3 than controls. The evidence of diastolic dysfunction, aortic root dimensions and history of aortic root surgery correlated with NT-proBNP and taurine levels. Alterations in serum levels of metabolism derived analytes link MFS pathophysiology with inflammation, oxidative stress and incipient cardiomyopathy.

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