Grip strength: are some adiposity phenotypes more detrimental than others? A Mendelian randomization study.

Objective: Our objective was to investigate causal associations of adiposity in different locations and metabolically favorable and unfavorable adiposity (MetFA and MetUFA, respectively) with grip strength.

Methods: Observational cross-sectional and Mendelian randomization (MR) (sex combined and stratified) analysis within UK Biobank (N ≤ 340,258) was used to assess the relationships of  visceral, abdominal subcutaneous, and gluteofemoral adipose tissue, anterior and posterior thigh muscle fat infiltration (ATMFI and PTMFI, respectively), body fat (BF) percentage, MetFA, and MetUFA with grip strength.

Results: In inverse variance weighted MR analysis, SD increases in BF, MetFA, and ATMFI were associated with lower grip strength by the following: -0.10 SD (95% CI: -0.16 to -0.04), -0.31 SD (95% CI: -0.45 to -0.18), and -0.05 SD (95% CI: -0.09 to -0.01), respectively. PTMFI associations aligned with ATMFI. Observational analyses were consistent for BF and ATMFI/PTMFI, but weighted median/mode MR corroborated findings for MetFA and ATMFI/PTMFI only. Higher visceral adipose tissue was associated with lower grip strength in observational analyses only. Associations for higher abdominal subcutaneous adipose tissue were inconsistent: Observational analyses suggested weaker grip; MR analyses suggested stronger grip, particularly in female individuals. There was no strong evidence in MR for associations with MetUFA or gluteofemoral adipose tissue.

Conclusions: Targeting fat infiltration in muscle may improve muscle function. MetFA appears to negatively impact muscle strength, requiring further investigation into underlying mechanisms.