A causal relationship between particulate matter 2.5 and obesity and its related indicators: a Mendelian...

In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM_2.5) on obesity, but their relationship remains ambiguous.

Utilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM_2.5 exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings.

The UVMR analysis demonstrated a significant association between PM_2.5 exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881-21.968; P _FDR = 0.005). Additionally, PM_2.5 concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244-2.776; P _FDR = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092-5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106-2.841; P _FDR = 0.019). Furthermore, PM_2.5 exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269-3.022; P _FDR = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34-4.649; P _FDR = 0.007). Finally, a significant negative association was observed between PM_2.5 concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025-0.89; P _FDR = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM_2.5 levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21.

Our MR study demonstrates conclusively that higher PM_2.5 concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.