Ghrelin-disrupting activity of arsenic and its relation to cardiometabolic diseases

Arsenic (As) exposure is linked to a special type of obesity without increasing body mass index. This obesity is accompanied by the reduction of skeletal muscle mass and elevation of insulin resistance (IR). Obesity and IR are the key risk factors for cardiometabolic diseases (CMDs). Ghrelin, a small peptide hormone, is linked to CMDs through multiple mechanisms. However, the ghrelin-disrupting activity of As and its implication in the promotion of CMDs has not yet been documented. Therefore, this study was designed to explore the association of As exposure with serum ghrelin levels and its relation to the risk of CMDs, particularly obesity, skeletal muscle mass reduction, and IR in the participants (n=421) selected from low- and high-As exposure rural areas in Bangladesh. The participants in high-exposure areas had a significantly lower median interquartile range of serum ghrelin levels than those in low-exposure area. Serum ghrelin levels of the participants were decreased with increasing concentrations of As in drinking water, hair, and nails. Ghrelin levels were inversely linked to obesity measures related to As exposure, including waist circumference, triceps skinfold thickness, and serum leptin levels. Decreased ghrelin levels were associated with the reduction of muscle mass measures, serum creatinine levels, and lean body mass. Ghrelin levels were decreased with increasing levels of insulin and IR as assessed by HOMA-IR. Furthermore, As-related HOMA-IR was significantly mediated by lowering the ghrelin levels. These findings collectively indicated that the ghrelin-disrupting activity of As might be involved in the pathophysiology of As-promoted CMDs.