Whether Tsukushi (TSK) can protect against high-fat diet (HFD)-induced obesity and improve glucose metabolism remains controversial. Serum levels of TSK in the population have not been reported until now. We assessed the association among TSK level, TSKU genotype, and metabolic traits in humans.

Associations between serum TSK levels and metabolic traits were assessed in 144 Han Chinese individuals. Loci in the TSKU gene region were further genotyped in 11,022 individuals. The association between the loci and serum TSK level was evaluated using the additive genetic model. The association between the loci and their metabolic traits in humans were also verified.

Lower TSK levels were observed in obese subjects than in control subjects (median and interquartile range 17.78:12.07–23.28 vs. 23.81:12.54–34.56, P < 0.05). However, in obese subjects, TSK was positively associated with BMI (β ± SE: 0.63 ± 0.31, P = 0.049), visceral fat area (β ± SE: 12.15 ± 5.94, P = 0.011), and deterioration of glucose metabolism. We found that rs11236956 was associated with TSK level in obese subjects (β 95% CI 0.17, 0.07–0.26; P = 0.0007). There was also a significant association between rs11236956 and metabolic traits in our population.

Our findings showed that serum TSK levels were associated with metabolic disorders in obese subjects. We also identified rs11236956 to be associated with serum TSK levels in obese subjects and with metabolic disorders in the total population.