Nickel occupies the 28th spot in the periodic table. It is a brutal metal found naturally in air, water, and soil (1). Nickel is vital for microorganisms, plants, animals, and humans (2). Nickel deficiency can cause growth retardation and fecundity decline, impairment of specific senses, reduced iron absorption, and alteration of essential enzymes in animal tissues and organs, leading to various clinical changes (3–5). However, specific toxicity and carcinogenic properties are connected with excessive nickel. In humans, numerous health issues, including contact dermatitis, cardiovascular conditions, and lung and nasal cancer, can result from prolonged exposure to nickel (6). Nickel exposure most commonly occurs through respiratory inhalation (7), food and water intake (8), and skin absorption (9). With the extensive use of nickel-containing products in daily life (10), especially in medical devices (11), great attention is paid to nickel-related health issues.

Globally, obesity has become a severe public health issue (12). Research shows that 70% of American and 50% of Chinese adults are overweight or obese (13, 14). There are several diseases associated with obesity, such as hypertension (15), malignant tumors (16), and diabetes (17). Several investigations conducted during the COVID-19 pandemic also revealed that obese people with COVID-19 infection had much greater rates of severe illness and fatality than normal persons (18, 19). Since obesity constitutes a significant threat to health, a more profound knowledge of relevant factors of obesity is necessary. Recent studies have confirmed a correlation between urinary nickel and the prevalence of diabetes and high blood pressure (20, 21). As everyone knows, diabetes and high blood pressure are closely related to obesity, but the relationship between urinary nickel and obesity status is unclear (22).

Body mass index (BMI) can effectively assess the state of health, has the characteristics of simple, feasible, and non-invasive (23, 24), and is an essential indicator for the diagnosis of obesity. Waist circumference (WC) has become increasingly crucial in predicting death and morbidity in recent years, and the combination of WC and BMI has been emphasized in diagnosing obesity (25, 26). In this study, we conducted a cross-sectional study to explore the relationship between urinary nickel and obesity index (BMI and WC). To our knowledge, this is the first study to examine the relationship between obesity status and nickel exposure, which is of great significance to this field.

In this study, urinary nickel was evaluated concerning obesity status in the general population. Our results prove that urinary nickel positively correlates with BMI and WC among adult males but not females. In previous studies, heavy metal pollution is a significant cause of chronic inflammation and oxidative stress, of which nickel occupies a large part (31). Chronic inflammation and oxidative stress can destroy the normal function of cells by interacting. The effects lead to symptoms such as weight gain or loss, decreased libido, physical pain, and emotional disorder, which pose a significant threat to health and lead to chronic inflammatory diseases, including obesity, diabetes, and cancer (32).

Several studies support our findings. Pokorska-Niewiada et al. showed that trace element disturbances, including nickel, can increase body mass index and contribute to endocrine disorders (33). A study from Spain found that the trace element nickel in fat is the highest, highlighting the potential role of nickel in obesity and obesity-related diseases (34). Another study from Turkey directly shows a positive correlation between BMI and nickel (35). The results of Yang et al. proved that men exposed to nickel were more prone to dyslipidemia and BMI ≥ 25 (36). In addition, when Cortés et al. studied the relationship between heavy metal exposure and chronic disease development in Chile, introducing BMI as a variable would confuse the relationship between IL-6 and nickel and increase the impact on individual inflammatory states by 40% at the same time. This study indirectly proves that nickel levels in the urine will affect BMI (37), it indirectly proves that nickel levels in the urine will affect BMI.

When subgroup analyzes were performed, we found that urinary nickel was independently and positively associated with BMI and WC in adult men. Numerous prior research had shown that nickel exposure damages male reproductive organs, which is strongly connected to oxidative stress, DNA damage, and hormonal imbalance (38–40). One study found gender differences in the inflammatory response of mice to the lung after nickel exposure, with the male being more susceptible to acute pneumonia and subchronic lung inflammation than females by a mechanism that induces increased neutrophil by CXCL1 and IL-6/STAT3 signaling pathways and enhanced monocyte infiltration by CXCL1 and CCL2 in male (41). At present, we have not found any other strong evidence for the reason for gender difference related to this study, and we suspect that the reason for the difference may be related to the differences in hormone levels, eating habits, and work stress between men and women. Large-sample prospective studies may be needed to explore this problem.

The precise mechanism of nickel exposure in BMI and WC is still unclear, but we try to clarify it from the following aspects. Firstly, in the hypothalamus, nickel exposure harms neurological function. As a result, hypothalamic neurons degenerate, paraventricular and supraoptic nuclei are reduced, and myeloperoxidase activity, nitric oxide increase, tumor necrosis factor-α and interleukin-1β of factors that promote inflammation ascend, which will affect the endocrine axis and might lead to hormonal imbalances (42, 43); Secondly, there is the possibility that nickel can affect the hypothalamic-pituitary-thyroid axis, causing abnormal thyroid activity (44). Finally, nickel disrupts the function of insulin β cells, resulting in abnormal glucose and lipid metabolism and affecting body weight (45, 46). Nickel exposure has also been linked to diabetes in some studies (20, 47).

Heavy metal contamination is everywhere—vegetables, seafood, meat and poultry, water sources, and household products are all at risk of exceeding heavy metal levels. Long-term nickel exposure causes irreparable harm to human system functioning, yet using nickel-related items in the medical, commercial, and industrial sectors continues to grow fast. The national legislature should reinforce and enhance the pertinent laws and regulations to minimize heavy metal contamination. Our study demonstrated a significant association between nickel exposure and BMI and WC in males, and men with long-term nickel exposure must pay particular attention to this health risk. In addition, the mechanism through which nickel exposure lowers male sperm quality is conclusive, and men with reproductive needs should avoid nickel-related industries. We appeal to the public to reduce exposure to heavy metals, especially nickel.

As a result of the large sample size, valid subgroup analyses were possible. However, some limitations need attention. In terms of screening for overweight and obesity, BMI and WC are highly specific, but they are less sensitive when used to identify adiposity due to their inability to discern fat distribution accurately; higher visceral fat is far more harmful than more fat in areas such as the thighs, and therefore may incorrectly classify a person as unhealthy or at a high-risk category for disease (48). Likewise, a higher BMI may also be induced by increased muscle mass, which may not always indicate obesity (49). Additionally, these two indicators do not account for a multiplicity of characteristics like gender and age. It is well-known that men and women have varying quantities of muscle, which might alter the final indicator findings. Individuals with a high percentage of body fat may create more angiotensin and aldosterone, while muscle does not (50).

In adult males, both BMI and WC were positively associated with urinary nickel. It is essential for adult men, especially those who are already obese, to reduce their nickel exposure. With the continued growth of nickel applications, nickel-related research will be expanded in the future, and our study may give suggestions for future studies in some specific aspects. Meanwhile, there is a need for further research to understand how urinary nickel might influence BMI and WC.

The original contributions presented in the study are publicly available. This data can be found here: www.cdc.gov/nchs/nhanes/.

Participation in the study was voluntary, and National Center for Health Statistics Research Ethics Review Board approved the study's conduct. To protect everyone's privacy, NHANES will anonymize collected data before making it public as public data. It is our agreement to follow all guidelines for using NHANES data for research purposes, as well as comply with all applicable standards and laws. The patients/participants provided their written informed consent to participate in this study.

Conceptualization: H-LL, D-LL, and S-FC. Methodology and Writing—review and editing: G-XW. Software: B-LH. Formal analysis: G-XW and B-LH. Writing—original draft preparation: B-LH. Visualization: J-TL and Z-BF. Supervision: L-YF, H-XZ, H-LL, D-LL, and S-FC. Funding acquisition: S-FC. All authors have read and agreed to the published version of the manuscript.