Endocrinology and Metabolism

Original Articles

Link between Circulating CCL2 Levels and Sarcopenia: Evidence from a Cohort Study, the UK Biobank, and Human GTEx Transcriptomic Data: Mi Kyung Kwak, Sung-Jin Kim, So Jeong Park, Tam Dao, Ji Yeon Baek, Dongryeol Ryu, June Yeon Kim, Geon Young Jang, Eunju Lee, Hyuk Sakong, Yuna Lee, Eun-Gyoung Hong, Yunju Jo, Beom-Jun Kim; Received March 29, 2026 Accepted June 17, 2026 Published online October 15, 2026; DOI: https://doi.org/10.3803/EnM.2026.3058 [Epub ahead of print]

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Abstract PDF: Background
Chronic inflammation is a hallmark of aging, but the role of inflammatory mediators such as C-C motif chemokine ligand 2 (CCL2) in skeletal muscle health remains unclear. Although CCL2 is often considered a detrimental pro-aging factor, it is also essential for myogenesis. This study aimed to clarify the complex role of CCL2 in human muscle metabolism.
Methods
We used a multimodal approach integrating clinical, proteomic, transcriptomic, and genetic analyses. The association between circulating CCL2 and sarcopenia-related parameters was examined in 323 community-dwelling older adults and validated using UK Biobank data (n=54,219). Genotype-Tissue Expression (GTEx) transcriptomic data (n=818) were used for tissue-level analysis, and Mendelian randomization (MR) was performed to assess causality.
Results
In the cohort study, serum CCL2 levels were significantly higher in participants with sarcopenia, weak muscle strength, or poor physical performance (P<0.001 to 0.042) and were inversely correlated with skeletal muscle index, grip strength, and gait speed (P<0.001 to 0.003). Each standard deviation increase in circulating CCL2 level was associated with 1.37–1.71-fold higher odds of sarcopenia-related outcomes (all P≤0.028). UK Biobank data also showed higher plasma CCL2 levels in participants with sarcopenia (P=0.005). In contrast to these observational findings, tissue-level analysis using GTEx data showed that higher skeletal muscle CCL2 expression was correlated with greater muscle cross-sectional area. MR further supported an inverse causal association between genetically predicted plasma CCL2 levels and sarcopenia risk (P=0.029).
Conclusion
These divergent findings raise the possibility that elevated circulating CCL2 levels in sarcopenia reflect a compensatory response to muscle deterioration rather than a direct pathogenic driver, highlighting the need for further mechanistic validation.

Diabetes, obesity and metabolism
Associations between Metabolic Syndrome Indicators and Colon Polyps: A Mendelian Randomization Study: Dongya Chen, Hong Xu, Zhaolin Zhang, Fang Chen, Qingqing Lu, Feng Pan; Endocrinol Metab. 2026;41(2):256-266. Published online January 22, 2026; DOI: https://doi.org/10.3803/EnM.2025.2379

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Abstract PDF Supplementary Material PubReader ePub: Background
While observational studies have suggested a potential link between metabolic syndrome (MetS) and an increased risk of colon polyps, the causal nature of this association remains uncertain. This study used a two-sample Mendelian randomization (MR) approach to evaluate the relationship between MetS and colon polyps.
Methods
A two-sample MR analysis was performed using data on MetS, its indicators, and colon polyps obtained from publicly available genome-wide association studies in the Integrative Epidemiology Unit (IEU) and MAGIC databases. Outliers were removed using Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), followed by MR calculations and false discovery rate (FDR) correction. The primary analysis was conducted with the inverse variance-weighted (IVW) method.
Results
The IVW results indicated no association between hypertension, hyperlipidemia, or diabetes and the risk of colon polyps. High-density lipoprotein cholesterol (HDL-C) (P=0.005), 2-hour glucose (P=0.004), glycated hemoglobin A1c (P=0.004), and the ratio of omega-6 to omega-3 fatty acids (P<0.001) were negatively associated with colon polyps. Conversely, body mass index (BMI) (P<0.001), body fat percentage (P=0.002), waist-to-hip ratio adjusted for BMI (P=0.001), total cholesterol (TC) (P=0.002), triglycerides (TG) (P<0.001), and both omega-3 (P<0.001) and omega-6 fatty acid levels (P=0.02) were positively associated with colon polyps. The relationships between these metabolic indicators and colon polyps remained significant after FDR correction.
Conclusion
Obesity-related traits, TC, and TG may increase the risk of colon polyps, while HDL-C may have a protective effect.

Brief Report

Diabetes, obesity and metabolism
Causal Associations of Cardiovascular Proteins and Diabetic Nephropathy Revealed by Mediation and Phenome-Wide Mendelian Randomization: Lei Chen, Yongdi Zuo, Manrong He, Jingxue Du, Wanxin Tang; Endocrinol Metab. 2025;40(5):781-786. Published online May 19, 2025; DOI: https://doi.org/10.3803/EnM.2024.2207

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Abstract PDF Supplementary Material PubReader ePub: Cardiovascular factors play a critical role in the progression of diabetic nephropathy (DN). This study utilized Mendelian randomization analysis to explore the causal relationships among cardiovascular proteins, risk factors, and DN. Using cis-protein quantitative trait loci (cis-pQTL) data for 90 cardiovascular proteins, we identified C-X3-C motif chemokine ligand 1 (CX3CL1) and colony-stimulating factor-1 (CSF-1) as potential therapeutic targets for DN. CX3CL1 was found to increase DN risk through mechanisms involving body mass index, fasting insulin, and hypertension. Conversely, CSF-1 appeared to protect against DN by reducing the number of monocytes expressing high levels of human leukocyte antigen. Additionally, targeting CX3CL1 could lower the risk of DN as well as other conditions, including acute renal injury, pituitary disorders, and necrotizing vasculopathies. These results highlight CX3CL1 and CSF-1 as promising novel therapeutic targets for DN.

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