Association between nickel and multiple metabolic outcomes: The mediating roles of lipid metabolism and inflammation

The relationship between nickel exposure and metabolic disease remains unclear, the study aims to investigate the association between nickel exposure and various metabolic disease outcomes and elucidate potential underlying mechanisms. Using data from the 2017–2018 National Health and Nutrition Exam...

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Main Authors: Zuqiang Fu, Shijie Zhou, Zhenkun Weng, Geyu Liang, Aihua Gu
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325006104
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author Zuqiang Fu
Shijie Zhou
Zhenkun Weng
Geyu Liang
Aihua Gu
author_facet Zuqiang Fu
Shijie Zhou
Zhenkun Weng
Geyu Liang
Aihua Gu
author_sort Zuqiang Fu
collection DOAJ
description The relationship between nickel exposure and metabolic disease remains unclear, the study aims to investigate the association between nickel exposure and various metabolic disease outcomes and elucidate potential underlying mechanisms. Using data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES), we evaluated nickel exposure in relation to eight metabolic outcomes: coronary heart disease (CHD), heart failure (HF), heart arrest (HA), angina, stroke, diabetes, hypertension, and chronic kidney disease (CKD). The findings demonstrated that each natural logarithm increase in urinary nickel concentration was significantly associated with higher risk of HF (OR=1.663, 95 % CI: 1.000–2.765), diabetes (OR=1.713, 95 % CI: 1.341–2.187), and CKD (OR=1.347, 95 % CI: 1.078–1.683). Furthermore, individuals with higher nickel exposure demonstrated an elevated risk of CHD (OR=2.439, 95 % CI: 1.008–5.903, P-trend=0.046) and diabetes (OR=2.494, 95 % CI: 1.526–4.075, P-trend<0.001) in a dose-dependent manner. Restricted cubic spline analyses showed no evidence of nonlinear associations between nickel exposure and other outcomes (all P > 0.05). Mediation analyses identified lipid metabolism disruption as a significant mediator for nickel's effects on CHD (Low density lipoprotein cholesterol [LDL-C], 9.76 %, P = 0.040; Total cholesterol [TC], 18.75 %, P < 2 ×10−16) and HF (LDL-C, 16.60 %, P = 0.040). Inflammatory activation mediated the relationship between nickel and CKD (Lymphocyte/White blood cell [Lym/WBC], 10.56 %, P < 2 ×10−16; Monocyte/Lymphocyte [Mono/Lym], 10.19 %, P < 2 ×10−16). Notably, nickel-induced inflammatory responses also appeared to dysregulate lipid metabolism, potentially contributing to diabetes risk (LDL-C, 26.35 %, P < 2 ×10−16; TC, 15.27 %, P < 2 ×10−16; Neutrophils/Lymphocyte [Neu/Lym], 2.42 %, P = 0.040). These results suggest that nickel exposure is associated with increased risks of CHD, HF, CKD, and diabetes, potentially through mechanisms involving lipid metabolism disturbances and inflammatory activation.
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spelling doaj-art-aae3cf942feb47f485d4cc394b681f922025-08-20T03:54:07ZengElsevierEcotoxicology and Environmental Safety0147-65132025-06-0129811827410.1016/j.ecoenv.2025.118274Association between nickel and multiple metabolic outcomes: The mediating roles of lipid metabolism and inflammationZuqiang Fu0Shijie Zhou1Zhenkun Weng2Geyu Liang3Aihua Gu4School of Public Health, Southeast University, Nanjing 21009, China; State Key Laboratory of Reproductive Medicine and Offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Environmental Health Risk Assessment Engineering Research Center, Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine and Offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Environmental Health Risk Assessment Engineering Research Center, Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine and Offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Environmental Health Risk Assessment Engineering Research Center, Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing 211166, ChinaSchool of Public Health, Southeast University, Nanjing 21009, ChinaSchool of Public Health, Southeast University, Nanjing 21009, China; State Key Laboratory of Reproductive Medicine and Offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Environmental Health Risk Assessment Engineering Research Center, Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing 211166, China; Correspondence to: School of Public Health, Southeast University, No. 87 Dingjiaqiao, Nanjing 210009, China.The relationship between nickel exposure and metabolic disease remains unclear, the study aims to investigate the association between nickel exposure and various metabolic disease outcomes and elucidate potential underlying mechanisms. Using data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES), we evaluated nickel exposure in relation to eight metabolic outcomes: coronary heart disease (CHD), heart failure (HF), heart arrest (HA), angina, stroke, diabetes, hypertension, and chronic kidney disease (CKD). The findings demonstrated that each natural logarithm increase in urinary nickel concentration was significantly associated with higher risk of HF (OR=1.663, 95 % CI: 1.000–2.765), diabetes (OR=1.713, 95 % CI: 1.341–2.187), and CKD (OR=1.347, 95 % CI: 1.078–1.683). Furthermore, individuals with higher nickel exposure demonstrated an elevated risk of CHD (OR=2.439, 95 % CI: 1.008–5.903, P-trend=0.046) and diabetes (OR=2.494, 95 % CI: 1.526–4.075, P-trend<0.001) in a dose-dependent manner. Restricted cubic spline analyses showed no evidence of nonlinear associations between nickel exposure and other outcomes (all P > 0.05). Mediation analyses identified lipid metabolism disruption as a significant mediator for nickel's effects on CHD (Low density lipoprotein cholesterol [LDL-C], 9.76 %, P = 0.040; Total cholesterol [TC], 18.75 %, P < 2 ×10−16) and HF (LDL-C, 16.60 %, P = 0.040). Inflammatory activation mediated the relationship between nickel and CKD (Lymphocyte/White blood cell [Lym/WBC], 10.56 %, P < 2 ×10−16; Monocyte/Lymphocyte [Mono/Lym], 10.19 %, P < 2 ×10−16). Notably, nickel-induced inflammatory responses also appeared to dysregulate lipid metabolism, potentially contributing to diabetes risk (LDL-C, 26.35 %, P < 2 ×10−16; TC, 15.27 %, P < 2 ×10−16; Neutrophils/Lymphocyte [Neu/Lym], 2.42 %, P = 0.040). These results suggest that nickel exposure is associated with increased risks of CHD, HF, CKD, and diabetes, potentially through mechanisms involving lipid metabolism disturbances and inflammatory activation.http://www.sciencedirect.com/science/article/pii/S0147651325006104NickelMultiple metabolic diseasesMediation analysis
spellingShingle Zuqiang Fu
Shijie Zhou
Zhenkun Weng
Geyu Liang
Aihua Gu
Association between nickel and multiple metabolic outcomes: The mediating roles of lipid metabolism and inflammation
Ecotoxicology and Environmental Safety
Nickel
Multiple metabolic diseases
Mediation analysis
title Association between nickel and multiple metabolic outcomes: The mediating roles of lipid metabolism and inflammation
title_full Association between nickel and multiple metabolic outcomes: The mediating roles of lipid metabolism and inflammation
title_fullStr Association between nickel and multiple metabolic outcomes: The mediating roles of lipid metabolism and inflammation
title_full_unstemmed Association between nickel and multiple metabolic outcomes: The mediating roles of lipid metabolism and inflammation
title_short Association between nickel and multiple metabolic outcomes: The mediating roles of lipid metabolism and inflammation
title_sort association between nickel and multiple metabolic outcomes the mediating roles of lipid metabolism and inflammation
topic Nickel
Multiple metabolic diseases
Mediation analysis
url http://www.sciencedirect.com/science/article/pii/S0147651325006104
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