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

Int J Chron Obstruct Pulmon Dis. 2025 Mar 31:20:869-882. doi: 10.2147/COPD.S488523. eCollection 2025.

Abstract

Objective: 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: Mendelian randomization; chronic obstructive pulmonary disease; cross-section; fat; lung function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue* / physiopathology
  • Adiposity* / ethnology
  • Adiposity* / genetics
  • Adult
  • Aged
  • Cross-Sectional Studies
  • Female
  • Forced Expiratory Volume
  • Genetic Predisposition to Disease
  • Humans
  • Linear Models
  • Lung* / physiopathology
  • Male
  • Mendelian Randomization Analysis
  • Middle Aged
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / ethnology
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Pulmonary Disease, Chronic Obstructive* / physiopathology
  • Risk Assessment
  • Risk Factors
  • Vital Capacity