scholarly journals Chronic arsenic exposure impairs adaptive thermogenesis in male C57BL/6J mice

2020 ◽  
Vol 318 (5) ◽  
pp. E667-E677
Author(s):  
Felicia Castriota ◽  
Peter-James H. Zushin ◽  
Sylvia S. Sanchez ◽  
Rachael V. Phillips ◽  
Alan Hubbard ◽  
...  
Keyword(s):  
Drinking Water ◽  
Fatty Acid ◽  
Heat Production ◽  
Arsenic Exposure ◽  
Epidemiological Studies ◽  
Acid Oxidation ◽  
Sequencing Analysis ◽  
Adaptive Thermogenesis ◽  
Chronic Arsenic Exposure ◽  
Total Fat

The global prevalence of type 2 diabetes (T2D) has doubled since 1980. Human epidemiological studies support arsenic exposure as a risk factor for T2D, although the precise mechanism is unclear. We hypothesized that chronic arsenic ingestion alters glucose homeostasis by impairing adaptive thermogenesis, i.e., body heat production in cold environments. Arsenic is a pervasive environmental contaminant, with more than 200 million people worldwide currently exposed to arsenic-contaminated drinking water. Male C57BL/6J mice exposed to sodium arsenite in drinking water at 300 μg/L for 9 wk experienced significantly decreased metabolic heat production when acclimated to chronic cold tolerance testing, as evidenced by indirect calorimetry, despite no change in physical activity. Arsenic exposure increased total fat mass and subcutaneous inguinal white adipose tissue (iWAT) mass. RNA sequencing analysis of iWAT indicated that arsenic dysregulated mitochondrial processes, including fatty acid metabolism. Western blotting in WAT confirmed that arsenic significantly decreased TOMM20, a correlate of mitochondrial abundance; PGC1A, a master regulator of mitochondrial biogenesis; and, CPT1B, the rate-limiting step of fatty acid oxidation (FAO). Our findings show that chronic arsenic exposure impacts the mitochondrial proteins of thermogenic tissues involved in energy expenditure and substrate regulation, providing novel mechanistic evidence for arsenic’s role in T2D development.

Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking water

2006 ◽  
Vol 101 (2) ◽  
pp. 213-220 ◽  
Author(s):  
Blakely M. Adair ◽  
Edward E. Hudgens ◽  
Michael T. Schmitt ◽  
Rebecca L. Calderon ◽  
David J. Thomas
Keyword(s):  
Drinking Water ◽  
Arsenic Exposure ◽  
Total Arsenic ◽  
Chronic Arsenic Exposure

scholarly journals Chronic Arsenic Exposure through Drinking Water and Risk of Type 2 Diabetes Mellitus: A Study from Bangladesh

2018 ◽  
Vol 37 (1) ◽  
pp. 5-12 ◽  
Author(s):  
Mst Karimon Nesha ◽  
Md Nazrul Islam ◽  
Nira Ferdous ◽  
Fahid Bin Nazrul ◽  
Johannes J Rasker
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Drinking Water ◽  
Fasting Blood Glucose ◽  
Arsenic Exposure ◽  
Skin Lesions ◽  
World Health ◽  
Chronic Arsenic Exposure

The well-documented fact that chronic arsenic exposure can lead to skin lesions, atherosclerotic diseases and cancers. The findings of association between arsenic exposure and diabetes mellitus indicate additional risk to human health. The aim of this study was to observe the association of chronic arsenic exposure from drinking water and risk of development of type 2 diabetes mellitus. To this end, a cross-sectional study was conducted in Comilla district of Bangladesh where ground water is heavily contaminated with arsenic. The individuals unexposed to arsenic were recruited from the Jhenaidah district. People with arsenic-related skin lesions were defined as subjects exposed to arsenic. Diabetes was defined if fasting blood glucose (FBG)>6.1 mmol/L following World Health Organization (WHO) guidelines. The common odds ratio for diabetes mellitus among subjects exposed to arsenic was 3.5 (95% confidence interval 1.1-10.9). After adjustment for age, sex and BMI, the Mantel-Haenszel weighted prevalence ratio was 3.5 (95% CI: 1.1-11.1); 3.7 (95% CI: 1.1-11.8) and 4.4 (95% CI: 1.1-17.2) respectively. The indicated relationships were significant (P<0.05). The observations suggested, chronic arsenic exposure through drinking water may be a risk factor of type 2 diabetes mellitus. J Bangladesh Coll Phys Surg 2019; 37(1): 5-12

Medium- and Short-Chain L-3-Hydroxyl-Acetyl-Coenzyme A Deficiency: A New Identified Mutation in Four Cases

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S9-S9
Author(s):  
Sheng Feng ◽  
Deborah Cooper ◽  
Lu Tan ◽  
Gail Meyers ◽  
Michael Bennett
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Coenzyme A ◽  
Short Chain ◽  
Acid Oxidation ◽  
Sequencing Analysis ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Chain Acyl ◽  
Unusual Phenotype

Abstract Medium- and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase (M/SCHAD, SCHAD) deficiency is a mitochondrial fatty acid oxidation disorder (FAOD). This enzyme catalyzes the penultimate step in fatty acid oxidation, the NAD+ dependent conversion of L-3-hydroxyacyl-CoA to 3-ketoacyl-CoA for medium- and short-chain acyl-CoA intermediates (C4-C12). The clinical presentations of most patients are recurrent hypoglycemia associated with hyperinsulinism. We presented four infants with C4 acyl-carnitine elevation identified by newborn screening that also showed an unusual phenotype of congenital hypotonia and gross developmental delay. Enzymatic studies confirmed the disease. Sequencing analysis of all the HADH coding exons on the four patients revealed a homozygous variant of a novel change (c.908G>T, p.Gly303Val). Western blot analysis subsequently confirmed the lack of the SCHAD protein. In addition, there is another previously reported benign variant (c.257T>C) identified in three infants. Therefore, we postulate that the HADH variant (c.908G>T) is indeed pathogenic and associated with a severe phenotype as evidenced by the cases described herein. Population screening for the c.908G>T mutation suggests this mutation to be common among Puerto Ricans. We recommend that SCHAD deficiency is included as part of the differential diagnosis of all infants with congenital hypotonia.

scholarly journals Parental decisions, child health and valuation of avoiding arsenic in drinking water in rural Bangladesh

2014 ◽  
Vol 13 (1) ◽  
pp. 152-167 ◽  
Author(s):  
Sonia N. Aziz ◽  
Kevin J. Boyle ◽  
Tom Crocker
Keyword(s):  
Public Health ◽  
Drinking Water ◽  
Child Health ◽  
Health Hazard ◽  
Arsenic Exposure ◽  
Mitigation Measures ◽  
Limited Information ◽  
Protective Actions ◽  
Chronic Arsenic Exposure ◽  
Time Required

Arsenic contamination of groundwater in Bangladesh is a widespread public health hazard. Water sources without high arsenic levels are scarce, affecting people's availability for work and other activities when they have to seek safe water to drink. While children are particularly susceptible to chronic arsenic exposure, limited information and heavy constraints on resources may preclude people in developing countries from taking protective actions. Since parents are primary decision-makers for children, a model of stochastic decision-making analytically linking parent health and child health is used to frame the valuation of avoiding arsenic exposure using an averting behavior model. The results show that safe drinking water programs do work and that people do take protective actions. The results can help guide public health mitigation policies, and examine whether factors such as child health and time required for remediation have an effect on mitigation measures.

Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure

2008 ◽  
Vol 24 (4) ◽  
pp. 247-256 ◽  
Author(s):  
D Mishra ◽  
SJS Flora
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Drinking Water ◽  
Wistar Rats ◽  
Arsenic Exposure ◽  
Brain Regions ◽  
Single Strand ◽  
Male Wistar Rats ◽  
Chronic Arsenic Exposure ◽  
The Brain

Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain – parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50 ppm sodium arsenite in drinking water) for 10 months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

scholarly journals Single-cell RNA-seq Analysis Reveals That Prenatal Arsenic Exposure Results in Long-term, Adverse Effects on Immune Gene Expression in Response to Influenza A Infection

2020 ◽  
Vol 176 (2) ◽  
pp. 312-328 ◽  
Author(s):  
Kevin S Hsu ◽  
Britton C Goodale ◽  
Kenneth H Ely ◽  
Thomas H Hampton ◽  
Bruce A Stanton ◽  
...  
Keyword(s):  
Immune Response ◽  
Drinking Water ◽  
Single Cell ◽  
Influenza A ◽  
Arsenic Exposure ◽  
Innate Immune ◽  
Lung Damage ◽  
Health Concern ◽  
Immune Gene ◽  
Sequencing Analysis

Abstract Arsenic exposure via drinking water is a serious environmental health concern. Epidemiological studies suggest a strong association between prenatal arsenic exposure and subsequent childhood respiratory infections, as well as morbidity from respiratory diseases in adulthood, long after systemic clearance of arsenic. We investigated the impact of exclusive prenatal arsenic exposure on the inflammatory immune response and respiratory health after an adult influenza A virus (IAV) lung infection. C57BL/6J mice were exposed to 100 ppb sodium arsenite in utero, and subsequently infected with IAV (H1N1) after maturation to adulthood. Assessment of lung tissue and bronchoalveolar lavage fluid at various time points post-IAV infection reveals greater lung damage and inflammation in arsenic-exposed mice versus control mice. Single-cell RNA sequencing analysis of immune cells harvested from IAV-infected lungs suggests that the enhanced inflammatory response is mediated by dysregulation of innate immune function of monocyte-derived macrophages, neutrophils, natural killer cells, and alveolar macrophages. Our results suggest that prenatal arsenic exposure results in lasting effects on the adult host innate immune response to IAV infection, long after exposure to arsenic, leading to greater immunopathology. This study provides the first direct evidence that exclusive prenatal exposure to arsenic in drinking water causes predisposition to a hyperinflammatory response to IAV infection in adult mice, which is associated with significant lung damage.

scholarly journals Nonmalignant Respiratory Effects of Chronic Arsenic Exposure from Drinking Water among Never-Smokers in Bangladesh

2008 ◽  
Vol 116 (2) ◽  
pp. 190-195 ◽  
Author(s):  
Faruque Parvez ◽  
Yu Chen ◽  
Paul W. Brandt-Rauf ◽  
Alfred Bernard ◽  
Xavier Dumont ◽  
...  
Keyword(s):  
Drinking Water ◽  
Arsenic Exposure ◽  
Respiratory Effects ◽  
Chronic Arsenic Exposure ◽  
Never Smokers

scholarly journals Design of the oxygen and substrate pathways. IV. Partitioning energy provision from fatty acids.

1996 ◽  
Vol 199 (8) ◽  
pp. 1667-1674
Author(s):  
J M Weber ◽  
G Brichon ◽  
G Zwingelstein ◽  
G McClelland ◽  
C Saucedo ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Aerobic Capacity ◽  
Muscle Cells ◽  
Acid Oxidation ◽  
Structural Capacity ◽  
Intramuscular Triglyceride ◽  
Total Fat ◽  
Acid Pathway ◽  
Rate Limiting

This paper quantifies the fluxes of fatty acids through the pathways supplying muscle mitochondria with oxidative fuel in exercising dogs and goats. We used continuous infusions of 1-[14C]palmitate and indirect calorimetry to measure fatty acid supply from two sources: the circulation and the triglyceride stores within the muscle cells. Our goal was to determine maximal flux through these two branches of the lipid pathway as key functional parameters for testing the principle of symmorphosis, i.e. that structural capacity is quantitatively matched to functional demand in the oxidative substrate pathways. It is under these rate-limiting conditions that we predict that all of the structural capacity will be used. Maximal rates of fatty acid oxidation were reached at low exercise intensities of 40% Mo2max. Fatty acids from the circulation supplied only a small fraction (15-25%) of the total fat oxidized under these conditions. Although dogs were able to oxidize circulatory fatty acids faster than goats, maximal rates were not in proportion to the 2.2-fold difference in aerobic capacity between the two species. Dogs compensated for their relatively lower use of circulatory fatty acids by oxidizing more triglycerides from lipid droplets in their muscle cells. We conclude that fatty acids from intramuscular triglyceride stores are a major source of fuel during maximal rates of lipid oxidation. Furthermore, it is this branch of the fatty acid pathway that is adapted to the large difference in aerobic capacity between dogs and goats.

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