The Imbalance of Mitochondrial Homeostasis of Peripheral Blood-Derived Macrophages Mediated by MAFLD May Impair the Walking Ability of Elderly Patients with Osteopenia

Abstract

Introduction. Many Asian cohort studies have shown that nonalcoholic fatty liver disease (NAFLD), now renamed as metabolic dysfunction-associated fatty liver disease (MAFLD), increases the risk of osteoporosis, yet the effect of MAFLD on elderly patients with osteopenia (OPe) has not been reported. Objective. This study aimed to explore the influence of MAFLD on the function of macrophages in patients with OPe. Methods. A total of 107 elderly OPe patients with or without MAFLD who visited the Huadong Hospital Affiliated to Fudan University (Shanghai, China) between January 1st, 2021, and September 30th, 2021, were evaluated for an interviewer-assisted questionnaire, as well as clinical and biological assessments. Results. Comparing two groups of elderly patients with the same bone mass level, we found that the six-minute walking distance ( $P=0.012$ ) and short physical performance battery (SPPB) score ( $P=0.0029$ ) of the elderly OPe patients with MAFLD are worse than those in OPe patients without MAFLD. Our results confirmed that the mitochondrial reactive oxygen species (mtROS) in peripheral blood of OPe patients with MAFLD was significantly higher than those without. We also observed the mitochondrial metabolism level of peripheral blood-derived macrophages in the included patients and peripheral blood macrophages in patients with MAFLD with more unbalanced mitochondrial dynamics of macrophages, more weakened mitochondrial respiratory capacity, and greater mitochondrial microstructure damage, when compared with the elderly patients without MAFLD. Conclusions. To conclude, our data revealed that MAFLD itself may aggravate the inflammatory state in elderly OPe people due to mitochondrial homeostasis imbalance of peripheral blood macrophages. Damaged monocyte-macrophages might trigger attenuation of the walking ability of OPe patients.