TWEAK/Fn14 hypomethylation and higher plasma TWEAK and TNF-α levels are related to sarcopenic obesity in community-dwelling elderly in Xinjiang

• Published in: Medicine (Baltimore) Vol. 104; no. 27; p. e42937
• Main Authors: Ma, Lingling, Maimaitiwusiman, Zhuoya, Xuekelati, Saiyare, Halan, Buluhan, Liu, Jinling, Wang, Hongmei
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 04.07.2025
• Subjects: Aged; Aged, 80 and over; China - epidemiology; Cytokine TWEAK - blood; Cytokine TWEAK - genetics; DNA Methylation; Female; Humans; Independent Living; Male; Middle Aged; Obesity - blood; Obesity - complications; Obesity - genetics; Observational Study; Sarcopenia - blood; Sarcopenia - complications; Sarcopenia - genetics; Tumor Necrosis Factor-alpha - blood; TWEAK Receptor - blood; TWEAK Receptor - genetics; China; TWEAK/Fn14; community-dwelling elderly; TNF-α; sarcopenic obesity; methylation
• ISSN: 1536-5964; 0025-7974; 1536-5964
• DOI: 10.1097/MD.0000000000042937

Sarcopenic obesity is a primary factor contributing to the decline in the quality of life among the elderly in our country. Studies have shown that hypomethylation of tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) is associated with sarcopenia. Our research primarily explores whether this mechanism also affects the progression of sarcopenic obesity. A total of 120 subjects were grouped into the case (sarcopenic obesity) and control (non-sarcopenic and nonobese) groups, with 60 subjects in each group based on power test (medium effect size, power = 80%). Bisulfite sequencing was used to assess the methylation status of TWEAK/Fn14 in these subjects. ELISA was employed to measure the plasma concentrations of TWEAK, tumour necrosis factor-alpha (TNF-α), interleukin (IL)-4, IL-6, and IL-10. SPSS 17.0 and R software was used for statistical analysis, employing multiple logistic regression to adjust for residual confounding factors, and Student t tests for difference analysis. Compared to the case group, the control group had higher methylation levels at CpG20, CpG30 sites in TWEAK (P = .043 for both). Additionally, the control group showed higher methylation level at CpG25 site in Fn14 (P = .025). After adjusting for hypertension, diabetes, triglyceride levels, gender, and age, Student t tests covariance confirmed significant differences in the enrichment levels of TWEAK, TNF-α, IL-10, and IL-4 of patients in case group (PTWEAK = .017, PTNF-α < .001, PIL-10 = .010, PIL-4 = .016). Multivariate logistic regression analysis revealed that higher plasma levels of TWEAK and TNF-α were significantly associated with the incidence of sarcopenic obesity (odds ratios = 1.024, 95% confidence interval = 1.006-1.042; odds ratios = 2.537, 95% confidence interval = 1.697-3.793). This evidence suggested that hypomethylation of TWEAK/Fn14 also affected sarcopenic obesity progression. Increased enrichment of TWEAK and TNF-α in plasma, along with hypomethylation of TWEAK and Fn14, promotes the occurrence of sarcopenic obesity may affect occurrence of sarcopenic obesity.