Obesity Mediates the Association Between Serum Copper and Inflammation: A Cross-sectional and Mendelian Randomization Study

Copper is an important biological trace element, but its overexposure can be harmful to the human body. Herein, we aimed to assess the association between serum copper levels and inflammation. A total of 5231 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016. Participants with higher serum copper levels had higher values of systemic inflammation indexes. The concentration of high-sensitive C-reactive protein (hs-CRP) increased with serum copper concentration (β = 2.8, p < 0.001). Participants with high and very high copper levels had higher ORs (odds ratios) of having inflammation (high: OR 2.92 (0.77–11.04), p = 0.074; very high: OR 8.66 (3.18–23.54), p = 0.011), which were further exacerbated in people with diabetes and males. Body mass index (BMI) and body fat percentage are two main mediators in the association between serum copper and hs-CRP, accounting for 12.62% and 19.72%, respectively. The random-effects inverse variance-weighted (IVW) analysis revealed that there was a genetic causal relationship between serum copper and obesity (OR 1.15, p = 0.014). Our results suggest that serum copper is positively associated with inflammation, which may be mainly mediated by obesity.