Rationale: Sarcopenic obesity (SO), mainly seen in older adults, can also affect younger individuals with obesity. It seriously impairs physical, metabolic, and cardiovascular health, making it a public health issue. In people with obesity, SO is often underdiagnosed due to screening tools and methods not tailored to this group. Identifying at-risk individuals is essential to prevent sarcopenia and related disorders. Endocannabinoids (EC), lipid-derived molecules, help regulate body balance, especially in muscles, where they control growth and function. EC system overactivity is linked to obesity and muscle issues, suggesting EC may be SO biomarkers.

Methods: EC circulating levels (AEA, 2-AG) and related metabolites (OEA, PEA, LEA, SEA, DHEA, EPEA, POEA) were measured by LC-MS/MS in 130 women from the OBESAR cohort (age 54.8±6.3 years; BMI 44±6 kg/m²; weight 114.7±17 kg). Correlations were assessed between plasma EC levels and fatfree mass (FFM), fat mass (FM), and skeletal muscle mass (SMM). ANOVA was used to compare EC levels among patient groups, stratified by a composite SO score combining FM (%), handgrip strength (kg), and SMM (%), where a higher score indicated higher SO risk.

Results: FFM percentage was positively correlated with AEA, OEA (p<0.001) and POEA plasma levels (p<0.0001). FM percentage was negatively correlated with AEA, OEA (p<0.001) and POEA plasma levels (p<0.0001). High risk vs. low risk of SO was associated with increased plasma levels of AEA (8.1±0.3 vs. 6.3±0.3 ng/ml, p<0.01), OEA (6.2±0.2 vs. 4.9±0.3 ng/ml, p<0.01) and POEA (1.2±0.1 vs. 0.6±0.1 ng/ml, p<0.001).