Associations of Skeletal Muscle Mass, Muscle Fat Infiltration, Mitochondrial Energetics, and Cardiorespiratory Fitness With Liver Fat Among Older Adults

Background: Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults. Methods: We associated comprehensive muscle-related phenotypes including muscle mass normalized to body weight (D-creatine dilution), muscle fat infiltration (magnetic resonance imaging), carbohydrate-supported muscle mitochondrial maximal oxidative phosphorylation (respirometry), and cardiorespiratory fitness (VO peak) with liver fat among older adults. Linear regression models adjusted for age, gender, technician (respirometry only), daily minutes of moderate-to-vigorous physical activity, and prediabetes/diabetes status tested main effects and interactions of each independent variable with waist circumference (high: women - ≥88 cm, men - ≥102 cm) and gender. Results: Among older adults aged 75 (interquartile range: 73, 79 years; 59.8% women), muscle mass and liver fat were not associated overall (N = 362) but were positively associated among participants with a high waist circumference (β: 25.2; 95% confidence intervals [95% CI]: 11.7, 40.4; p = .0002; N = 160). Muscle fat infiltration and liver fat were positively associated (β: 15.2; 95% CI: 6.8, 24.3; p = .0003; N = 378). Carbohydrate-supported maximum oxidative phosphorylation (before adjustment) and VO peak (after adjustment; β: -12.9; 95% CI: -20.3, -4.8; p = .003; N = 361) were inversely associated with liver fat; adjustment attenuated the estimate for maximum oxidative phosphorylation although the point estimate remained negative (β: -4.0; 95% CI: -11.6, 4.2; p = .32; N = 321). Conclusions: Skeletal muscle-related characteristics are metabolically relevant factors linked to liver fat in older adults. Future research should confirm our results to determine whether trials targeting mechanisms common to liver and muscle fat accumulation are warranted.