The association between visceral adipose tissue, serum urate, and hepatic fat deposition: a post-hoc analysis from the Habitual Diet vs. Avocado randomized control trial

Abstract Background Hyperuricemia, while associated with, is not part of the metabolic syndrome. We sought to examine the association between central obesity as measured by visceral abdominal tissue (VAT) deposition and serum urate (SU). We further explored the association between SU and hepatic fat deposition (HFD). Methods Through a post-hoc analysis, using a single study site from the Habitual Diet vs. Avocado (HAT) multi-center randomized control trial, baseline serum, abdominal magnetic resonance imaging (MRI) and responses to questionnaires were available. Means, medians and proportions were used to describe variables. Anova, and Chi-square were used to describe bivariate associations between VAT and SU as well as SU and HFD. Generalized linear models (linear or logistic) were used to describe above associations while controlling for other potential metabolic confounders. Principal component analyses were used to evaluate the fit of SU with the other metabolic variables. Trial registration The parent habitual diet avocado trial was registered with clinical trials.gov with the following protocol, NCT03528031. Results The baseline cohort of 223 subjects were mostly female (80%) with mean age of 46 years and BMI of 33, (65% were obese), 25% had high urate (SU > 360 µmol/L). SU was strongly correlated with VAT deposits ( r = 0.31, p <0.0001) and HFD ( r = 0.23, p = 0. 0005). Subjects with SU > 360 μmol/L were more likely to be male, obese (BMI > 30), morbidly obese (BMI > 40), and have greater amounts of VAT deposits. More than two-thirds (71%) of subjects with hyperuricemia had elevated HFD (HFD > 5%) compared to 41% of subjects with normal SU (p < 0.0001). After controlling for potential confounding covariates, including BMI, the association between VAT and SU was attenuated potentially through mediating factors associated with covariates. SU > 360 μmol/L remained strongly associated with HFD > 5%, (Odds Ratio = 3.0, p = 0.005) after adjusting for BMI and other confounders. Conclusions For this cohort of subjects with known central adiposity, higher SU levels were associated with greater deposits of VAT strengthening the association between SU > 360 μmol/L and metabolic syndrome. SU > 360 μmol/L was also associated with higher proportion of HFD. As a limitation of this post-hoc cross-sectional design, causation (or directionality) cannot be assumed. The parent HAT clinical trial was registered under the approved clinical trial protocol, NCT03528031. Original submission, 04 May 2018. Final version, 17 March 2023.