Serum SH2B1 and SULT1A2 in relation to adiposity and early weight-loss response: a hypothesis-generating study.

BACKGROUND: Individual responses to weight loss interventions are highly heterogeneous. This study aimed to explore the association between serum SULT1A2 and SH2B1 levels and weight loss responses, with the goal of generating biologically relevant hypotheses. METHODS: The first cohort consisted of 223 patients (102 normal weight, 52 overweight, and 69 obese), to assess associations of baselines SULT1A2 and SH2B1 with weight status. The second cohort included 49 eligible participants that completed a 4-week intermittent fasting-based weight management program. They were divided into greater weight loss group (weight loss ≥5% of initial body weight) and lesser weight loss group (weight loss <5%). Serum SULT1A2 and SH2B1 levels were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the first cohort, serum SULT1A2 and SH2B1 levels varied significantly across BMI groups (P = 0.002 and P = 0.013, respectively). Both biomarkers were elevated in the overweight group compared with the normal weight group (P < 0.01 and P < 0.05). The obese group had lower SULT1A2 and SH2B1 levels than the overweight group (P < 0.05), with no significant differences versus the normal weight group. In the second cohort, SULT1A2 exhibited no association with weight loss response across both sexes. For SH2B1, male greater weight loss group exhibited significantly higher levels than lesser weight loss group (2477.1 ± 1332.2 vs. 1298.4 ± 649.6 ng/mL, P = 0.030, Hedges' g = 0.97, 95% CI: 0.01-1.97); however, this association was attenuated and did not persist after multivariable adjustment for age and baseline BMI. In females, no such difference was observed (1325.0 ± 812.3 vs. 1135.7 ± 488.3 ng/mL, P = 0.471, Hedges' g = 0.25, 95% CI: -0.49-0.99). CONCLUSIONS: Circulating SULT1A2 and SH2B1 vary across adiposity phenotypes, suggesting their potential involvement in energy metabolism. Baseline SH2B1 showed a male-specific exploratory association with early weight-loss response, although this finding was not independent of age and BMI. Collectively, these results support SH2B1 as a candidate peripheral marker of further investigation in larger, independent cohorts.