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

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI:10.1016/j.taap.2025.117676

Kamrun Nahar Rossi , Faysal Abedin , Nayan Chandra Mohanto , Biplob Ahmed , Sobuj Mia , Nesar Uddin , Rajoana Karim Rimi , Osman Goni , Sharon Jahan Sarder , Sajib Hossain , Mainul Islam , Ahsanul Mahbub Jubayar , Md Shofikul Islam , Shakhawoat Hossain , Md Ashraful Hoque , Daigo Sumi , Zahangir Alam Saud , Seiichiro Himeno , Khaled Hossain

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Abstract

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.

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砷的胃饥饿素破坏活性及其与心脏代谢疾病的关系。

砷（As）暴露与一种特殊类型的肥胖有关，而不会增加体重指数。这种肥胖伴随着骨骼肌量的减少和胰岛素抵抗（IR）的升高。肥胖和IR是心血管代谢疾病的主要危险因素。胃饥饿素是一种小的肽激素，通过多种机制与cmd联系在一起。然而，As的胃饥饿素破坏活性及其在促进cmd中的意义尚未得到证实。因此，本研究旨在探讨砷暴露与血清胃饥饿素水平的关系及其与cmd风险的关系，特别是在孟加拉国农村低砷暴露和高砷暴露的参与者（n = 421）中肥胖、骨骼肌质量减少和IR的关系。高暴露地区的参与者血清胃饥饿素水平的中位数四分位数范围明显低于低暴露地区的参与者。受试者的血清生长素水平随着饮用水、头发和指甲中砷浓度的增加而降低。胃饥饿素水平与砷暴露相关的肥胖指标呈负相关，包括腰围、肱三头肌皮褶厚度和血清瘦素水平。胃饥饿素水平的降低与肌肉量、血清肌酐水平和瘦体重的减少有关。经HOMA-IR评估，胃饥饿素水平随着胰岛素和IR水平的升高而降低。此外，as相关的HOMA-IR可通过降低胃饥饿素水平而显著调节。这些发现共同表明，As的生长素破坏活性可能参与了As促进的cmd的病理生理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.