Metabolically healthy obesity increases the risks of MASLD and hyperuricemia: a cohort study with mediation analysis

Although metabolically healthy obesity (MHO) is often regarded as a relatively benign phenotype, its association with the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) and hyperuricemia remains unclear. This study examined the associations between MHO and other metabolic-obesity phenotypes with MASLD and hyperuricemia, and explored the mediating roles of metabolic indicators. This study included 11,712 and 13,846 participants from a health examination cohort at the First Affiliated Hospital of Ningbo University for MASLD and hyperuricemia analyses, respectively. Participants were classified into four metabolic-obesity phenotypes, with MHO defined as obesity without metabolic syndrome components. Cox regression and mediation analyses were performed to examine the associations and the proportions explained by metabolic indicators. During a 7-year follow-up period, 3,756 MASLD and 3,294 hyperuricemia cases were identified. Compared with the metabolically healthy non-obese group, individuals with MHO exhibited significantly higher risks of MASLD (hazard ratio [HR] = 3.54, 95% confidence interval [CI]: 3.09–4.05) and hyperuricemia (HR = 1.92, 95% CI: 1.65–2.23). Mediation analysis illustrated that the triglyceride glucose index accounted for 16.2% and 13.8% of the total effects, while other indicators also contributed to the associations to varying degrees. MHO is associated with an increased risk of MASLD and hyperuricemia, partly explained by metabolic indicators. Greater attention to these indicators may facilitate earlier risk identification and more effective prevention. NCT07001865; Registration date: May 25, 2025; ClinicalTrials.gov.