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An interaction of inorganic arsenic exposure with body weight and composition on type 2 diabetes indicators in Diversity Outbred mice.

ABSTRACT: Type 2 diabetes (T2D) is a complex metabolic disorder with no cure and high morbidity. Exposure to inorganic arsenic (iAs), a ubiquitous environmental contaminant, is associated with increased T2D risk. Despite growing evidence linking iAs exposure to T2D, the factors underlying inter-individual differences in susceptibility remain unclear. This study examined the interaction between chronic iAs exposure and body composition in a cohort of 75 Diversity Outbred mice. The study design mimics that of an exposed human population where the genetic diversity of the mice provides the variation in response, in contrast to a design that includes untreated mice. Male mice were exposed to iAs in drinking water (100 ppb) for 26 weeks. Metabolic indicators used as diabetes surrogates included fasting blood glucose and plasma insulin (FBG, FPI), blood glucose and plasma insulin 15 min after glucose challenge (BG15, PI15), homeostatic model assessment for [Formula: see text]-cell function and insulin resistance (HOMA-B, HOMA-IR), and insulinogenic index. Body composition was determined using magnetic resonance imaging, and the concentrations of iAs and its methylated metabolites were measured in liver and urine. Associations between cumulative iAs consumption and FPI, PI15, HOMA-B, and HOMA-IR manifested as significant interactions between iAs and body weight/composition. Arsenic speciation analyses in liver and urine suggest little variation in the mice's ability to metabolize iAs. The observed interactions accord with current research aiming to disentangle the effects of multiple complex factors on T2D risk, highlighting the need for further research on iAs metabolism and its consequences in genetically diverse mouse strains.

SUBMITTER: Xenakis JG

PROVIDER: S-EPMC9761582 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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An interaction of inorganic arsenic exposure with body weight and composition on type 2 diabetes indicators in Diversity Outbred mice.

Xenakis James G JG Douillet Christelle C Bell Timothy A TA Hock Pablo P Farrington Joseph J Liu Tianyi T Murphy Caroline E Y CEY Saraswatula Avani A Shaw Ginger D GD Nativio Gustavo G Shi Qing Q Venkatratnam Abhishek A Zou Fei F Fry Rebecca C RC Stýblo Miroslav M Pardo-Manuel de Villena Fernando F

Mammalian genome : official journal of the International Mammalian Genome Society 20220711 4

Type 2 diabetes (T2D) is a complex metabolic disorder with no cure and high morbidity. Exposure to inorganic arsenic (iAs), a ubiquitous environmental contaminant, is associated with increased T2D risk. Despite growing evidence linking iAs exposure to T2D, the factors underlying inter-individual differences in susceptibility remain unclear. This study examined the interaction between chronic iAs exposure and body composition in a cohort of 75 Diversity Outbred mice. The study design mimics that ...[more]

PMID: 35819478

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Project description:Following an official request to EFSA from the European Commission, EFSA assessed the chronic dietary exposure to inorganic arsenic (iAs) in the European population. A total of 13,608 analytical results on iAs were considered in the current assessment (7,623 corresponding to drinking water and 5,985 to different types of food). Samples were collected across Europe between 2013 and 2018. The highest mean dietary exposure estimates at the lower bound (LB) were in toddlers (0.30 μg/kg body weight (bw) per day), and in both infants and toddlers (0.61 μg/kg bw per day) at the upper bound (UB). At the 95th percentile, the highest exposure estimates (LB-UB) were 0.58 and 1.20 μg/kg bw per day in toddlers and infants, respectively. In general, UB estimates were two to three times higher than LB estimates. The mean dietary exposure estimates (LB) were overall below the range of benchmark dose lower confidence limit (BMDL 01) values of 0.3-8 μg/kg bw per day established by the EFSA Panel on Contaminants in the Food Chain in 2009. However, for the 95th percentile dietary exposure (LB), the maximum estimates for infants, toddlers and other children were within this range of BMDL 01 values. Across the different age classes, the main contributors to the dietary exposure to iAs (LB) were 'Rice', 'Rice-based products', 'Grains and grain-based products (no rice)' and 'Drinking water'. Different ad hoc exposure scenarios (e.g. consumption of rice-based formulae) showed dietary exposure estimates in average and for high consumers close to or within the range of BMDL 01 values. The main uncertainties associated with the dietary exposure estimations refer to the impact of using the substitution method to treat the left-censored data (LB-UB differences), to the lack of information (consumption and occurrence) on some iAs-containing ingredients in specific food groups, and to the effect of food preparation on the iAs levels. Recommendations were addressed to improve future dietary exposure assessments to iAs.

Dataset Information

An interaction of inorganic arsenic exposure with body weight and composition on type 2 diabetes indicators in Diversity Outbred mice.

Publications

An interaction of inorganic arsenic exposure with body weight and composition on type 2 diabetes indicators in Diversity Outbred mice.

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