Arsenic Secondary Methylation Capacity Is Inversely Associated with Arsenic Exposure-Related Muscle Mass Reduction

Abstract

Skeletal muscle mass reduction has been implicated in insulin resistance (IR) that promotes cardiometabolic diseases. We have previously reported that arsenic exposure increases IR concomitantly with the reduction of skeletal muscle mass among individuals exposed to arsenic. The arsenic methylation capacity is linked to the susceptibility to some arsenic exposure-related diseases. However, it remains unknown whether the arsenic methylation capacity affects the arsenic-induced reduction of muscle mass and elevation of IR. Therefore, this study examined the associations between the arsenic methylation status and skeletal muscle mass measures with regard to IR by recruiting 437 participants from low- and high-arsenic exposure areas in Bangladesh. The subjects’ skeletal muscle mass was estimated by their lean body mass (LBM) and serum creatinine levels. Subjects’ drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and the percentages of MMA, as well as inversely associated with the percentages of DMA and the secondary methylation index (SMI). Subjects’ LBM and serum creatinine levels were positively associated with the percentage of DMA and SMI, as well as inversely associated with the percentage of MMA. HOMA-IR showed an inverse association with SMI, with a confounding effect of sex. Our results suggest that reduced secondary methylation capacity is involved in the arsenic-induced skeletal muscle loss that may be implicated in arsenic-induced IR and cardiometabolic diseases.

Chronic arsenite exposure induced skeletal muscle atrophy by disrupting angiotensin II‐melatonin axis in rats

“…Epidemiological and animal studies have shown that arsenic exposure is associated with skeletal muscle mass loss and atrophy 8–12 . A previous in vivo study showed that exposure to 0.5 ppm As 2 O 3 for 4 weeks induced skeletal muscle atrophy in mice 37 .…”

“…Epidemiological and animal studies have shown that arsenic exposure is associated with skeletal muscle mass loss and atrophy. [8][9][10][11][12] A previous in vivo study showed that exposure to 0.5 ppm As 2 O 3 for 4 weeks induced skeletal muscle atrophy in mice. 37 The results of this study showed that exposure to 10 ppm arsenite for 3 months had no significant impact on skeletal muscle, while exposure to arsenite for 9 months caused significant loss of skeletal muscle mass and atrophy in rats.…”

“…Recent epidemiological studies have shown that arsenic exposure may be associated with loss of skeletal muscle mass in local residents from arsenic‐endemic areas of Bangladesh 8,9 . Studies have demonstrated that arsenic exposure induced skeletal muscle injury via generating more reactive oxygen species as well as restraining mitophagy and mitochondrial function in mice and duck 10–12 .…”

Reproductive-Toxicity-Related Endpoints in C. elegans Are Consistent with Reduced Concern for Dimethylarsinic Acid Exposure Relative to Inorganic Arsenic

“…GFP fluorescence is dependent on correct protein folding, and arsenic exposure results in protein misfolding [ 56 , 57 ]; therefore, the reduced green fluorescent signal in gravid adults exposed to 25 µg/mL or more NaAsO 2 could be due to conserved arsenite-induced protein unfolding. However, arsenic exposure in humans is also associated with reduced muscle mass [ 58 ], suggesting that the reduced GFP could have been caused by changes in C. elegans muscle mass or myo-3 gene expression.…”

Arsenic Exposure through Dietary Intake and Associated Health Hazards in the Middle East

“…As affects the gluconeogenesis in muscle cells by inhibiting glucose transporters and suppressing glucose metabolism regulatory genes. Hence, the glycolytic pathway and mitochondrial energy production are altered [ 132 , 133 ]. In experimental studies of mice, it has been reported that As decreases the functional capacity of muscle and destroys muscle progenitor cells [ 134 ].…”