Association of ß-glucuronidase activity with menopausal status, ethnicity, adiposity, and inflammation in women

Abstract

Objectives: Many dietary polyphenols with potential health-promoting benefits undergo hepatic conjugation and circulate as inactive glucuronides that can be cleaved by ß-glucuronidase to reform the bioactive aglycone. Although indirect evidence suggests estrogen may induce ß-glucuronidase, little is known about ß-glucuronidase regulation across women's reproductive lifespan. Correlates of serum ß-glucuronidase activity in healthy premenopausal versus postmenopausal women were therefore examined.

Methods: ß-Glucuronidase activity and C-reactive protein (CRP) were assayed in stored serum from the Women's Breast and Bone Density Study, and dual-energy x-ray absorptiometry and anthropometry assessed body composition. Participants were premenopausal (n = 133) or postmenopausal (n = 89), and Hispanic (37%) or non-Hispanic White (63%). Multivariate linear regression models tested associations between ß-glucuronidase and menopausal status, ethnicity, CRP, and body composition metrics, overall and stratified by menopausal status.

Results: Postmenopausal (vs premenopausal) women were older (60.4 ± 3.7 vs 44.8 ± 2.4 y) with a lower Hispanic ethnicity prevalence (27% vs 44%), and higher serum ß-glucuronidase activity (1.5 ± 0.8 vs 1.3 ± 0.5 U/L) and CRP (4.2 ± 4.4 vs 3.3 ± 4.7 mg/L). Adjusting for confounders, ß-glucuronidase was positively associated with Hispanic ethnicity, CRP, body mass index, and total fat mass (all, P < 0.01), but not menopausal status nor lean mass. Central adiposity measures were also positively associated with ß-glucuronidase with the same covariates.

Conclusions: ß-Glucuronidase enzyme activity, upon which polyphenol health-related benefits may depend, is not associated with menopausal status. Future studies are required to determine clinical significance and mechanisms driving ß-glucuronidase associations with ethnicity, inflammation, and adiposity in women.

Figure 1.

Schematic of hepatic glucuronidation, a well characterized phase II inactivation pathway for polyphenols and sex steroids, and enzyme-mediated deconjugation by ß-glucuronidase (GUSB) to restore the original bioactive aglycone.

Figure 2.

Box plots of GUSB in WBBD study participants by menopausal status or ethnicity. (A) GUSB did not significantly differ by menopausal status in a linear regression model adjusted for race/ethnicity, CRP (log), trunk fat, lean mass, and height: beta-coefficient, 0.046; p-value, 0.3. (B) Box plot of GUSB in WBBD study participants, by race/ethnicity. Hispanic women had significantly higher GUSB (log) than NHW women in a linear regression model adjusted for menopausal status, CRP (log), trunk fat, lean mass, and height: beta-coefficient, 0.144; p-value, 0.004. Plots depict medians and interquartile ranges.

Figure 3.

Unadjusted (dashed line) and adjusted (solid line) association between CRP and GUSB in WBBD study participants. In a linear regression model adjusted for menopausal status, race/ethnicity, trunk fat, lean mass, and height, CRP (log) is significantly positively associated with GUSB (log): beta-coefficient, 0.066; p-value, 0.007.

Figure 4.

Unadjusted (dashed line) and adjusted (solid line) association between BMI and GUSB in WBBD study participants. In a linear regression model adjusted for menopausal status, race/ethnicity, and CRP (log-transformed), BMI (log-transformed) is significantly associated with GUSB (log-transformed): beta-coefficient, 0.457; p-value, 0.003.

Figure 5.

Unadjusted (dashed line) and adjusted (solid line) association between measures of regional fat and GUSB in WBBD study participants in a linear regression model adjusted for menopausal status, race/ethnicity, CRP (log-transformed), lean soft tissue mass, and height. (A) fat mass is significantly associated with GUSB (log-transformed): beta-coefficient, 0.011; p-value, 0.006. (B) Waist circumference is significantly associated with GUSB (log-transformed): beta-coefficient, 0.014; p-value, < 0.001. (C) Trunk fat is significantly associated with GUSB (log-transformed): beta-coefficient, 0.029; p-value, < 0.001. (D) trunk-to-leg fat ratio is significantly associated with GUSB (log-transformed): beta-coefficient, 0.243; p-value, < 0.001.