Elucidating the Relationship Between Body Fat Index and Pulmonary Health: Insights from Cross-Sectional Analysis and Mendelian Randomization

Qing Zhang,1,&ast; Zihui Wang,1,&ast; Weijuan Liu,1,&ast; Guannan Cai,2,&ast; Yuan Gao,2 Yilin Chen,1 Yuan Han,3 Anliu Nie,1 Ruan Liang,1 Fei Cui,1 Ying Chen1 1Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 3School of Nursing, Guangzhou Medical university, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Chen, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, No. 28 Qiaozhong Zhong Road, Guangzhou, Guangdong, 510000, People’s Republic of China, Email [email protected] Fei Cui, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, No. 28 Qiaozhong Zhong Road, Guangzhou, Guangdong, 510000, People’s Republic of China, Email [email protected]: To evaluate the relationship between body fat index and pulmonary health.Methods: In the multiethnic population-based cross-sectional study, a multivariable linear regression model was adapted to assess the association of fat mass/percentage with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC). The Mendelian Randomization (MR) method was used to assess the causal associations of fat mass/percentage in specific body parts with FEV1 and COPD risk. Sensitivity analysis of MR was performed to assess the robustness of estimates.Results: In the cross-sectional analysis, a non-linear relationship was observed between fat mass and FEV1 without adjustment. After multivariate adjustment, the negative associations of fat mass/percentage with FEV1/FVC were found. In the MR study, genetically determined fat presented a negative causal effect on FEV1 (e.g., estimate = − 0.170, P < 0.001 for left leg fat mass). The causal associations of genetically determined body fat with clinical diagnosis COPD were also determined (e.g., OR = 1.936, P < 0.001 per 1.9 kilograms increase in left leg fat mass).Conclusion: We present strong evidence on the causal relationship between body fat mass/percentage and both the deterioration of lung function and the increased risk of COPD. Additional efforts are required to mitigate the negative effects of body fat.Keywords: fat, lung function, chronic obstructive pulmonary disease, cross-section, Mendelian randomization