The association between primary bile acids and metabolically unhealthy obesity

Dysregulation of bile acid (BA) profiles is closely associated with obesity and its related metabolic abnormalities. This study aims to investigate the BA alterations between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) and identify specific BA species associated with MUO.

We measured serum bile acid profiles in two cross-sectional studies. The discovery cohort included 261 normal-weight, 80 MHO, and 120 MUO individuals. The validation cohort, consisting of 104 MHO and 104 MUO participants (matched for age, sex, and BMI), was used for confirmation.

Individual primary bile acids (PBAs), including cholic acid, glycocholic acid, chenodeoxycholic acid, and total PBA concentration, were markedly increased in MUO compared with both normal-weight and MHO subjects. Total secondary bile acids were decreased in both obesity phenotypes compared with normal-weight subjects, but did not differ between MUO and MHO. Among individuals with obesity, either individual PBA or total PBA levels were positively correlated with metabolic deterioration parameters such as WHR, HOMA-IR, HbA1c, and TG. Moreover, a higher total PBA level was associated with an increased proportion of MUO. These findings were further replicated in the validation cohort.

Serum individual PBAs and total PBAs were significantly elevated in MUO compared with MHO. Higher PBA levels were associated with adverse metabolic parameters and an increased proportion of MUO. This study characterizes the distinct BA profiles across obesity phenotypes and highlights the associations between PBAs and MUO.