Mediating effects of lipid metabolic and inflammatory factors on skeletal muscle mass in adults: A cross-sectional study

Investigating the mediating effects of metabolic and inflammatory factors on skeletal muscle mass is essential, as these factors may help deepen understanding of the complex processes underlying skeletal muscle mass decline and support effective prevention and management in adults. Health examination data from 2277 participants who attended the health examination center of a provincial hospital in Taiyuan, China, between 2019 and 2023 were collected. Random forest analysis, correlation analysis, regression modeling, and mixed-effects structural equation modeling were used to identify determinants of appendicular skeletal muscle index (ASMI) and to examine metabolic and inflammatory mediating pathways. ASMI was significantly higher in obese participants than in nonobese participants ( P  < .001). Body mass index (BMI) was significantly positively correlated with ASMI ( r  = 0.68, P  < .001) and negatively associated with the risk of low skeletal muscle mass (OR = 0.53, 95% CI: 0.47–0.60). Structural equation modeling showed that BMI not only had a direct positive effect on ASMI, but also influenced ASMI through metabolic and inflammatory pathways. In the high-BMI group, lipid metabolism had a direct positive effect on ASMI ( β  = 0.08, P  < .001). In contrast, in the low-BMI group, lipid metabolism had a direct negative effect on ASMI ( β  = −0.08, P  < .001) and was also positively associated with ASMI through inflammatory pathways ( β  = 0.07, P  < .001). In this group, glucose metabolism ( β  = 0.24, P  < .001) and protein metabolism ( β  = −0.08, P  < .001) regulated lipid metabolism and indirectly influenced skeletal muscle mass through lipid metabolic pathways. BMI was significantly positively associated with ASMI, with its effects mainly mediated through lipid metabolism and inflammatory pathways, and the pathways differed across BMI groups. These findings highlight lipid metabolism and inflammation as key factors associated with muscle health, facilitating more accurate risk screening and the implementation of targeted prevention and management strategies.