Adiposity and plasma concentrations of kynurenine pathway metabolites and traditional markers of inflammation.

AIM:The kynurenine pathway is increasingly recognised to play a role in inflammation and disease. We assessed the cross-sectional and longitudinal associations of adiposity measures (body mass index, waist-hip ratio, waist circumference and fat mass ratio) with plasma concentrations of kynurenine pathway metabolites and traditional markers of inflammation. METHODS:We used data from 970 Melbourne Collaborative Cohort Study participants who had plasma markers measured at baseline (median age 59 years) and follow-up (median age 70 years). Linear regression was used to assess cross-sectional and longitudinal associations between four adiposity measures and concentrations of i) nine kynurenine pathway metabolites; ii) two derived markers; iii) eight traditional inflammatory markers. RESULTS:Cross-sectionally, most kynurenine metabolites were strongly associated with adiposity measures at both time points; associations were generally stronger than for most inflammation markers except CRP (e.g. body mass index at baseline, quinolinic acid (per S.D. β = 0.30, 95%CI: 0.24-0.36, P = 10-21), kynurenine (β = 0.25, 95%CI: 0.19-0.31, P = 10-16) and CRP (β = 0.31, 95%CI: 0.25-0.37, P = 10-24), and remained largely unchanged after adjustment for confounders. Longitudinally, changes in adiposity measures over approximately a decade were positively associated with changes in kynurenine metabolite concentrations (in particular for 3-hydroxyanthranilic acid, kynurenine and quinolinic acid), and more strongly so than for other markers of inflammation, including CRP. CONCLUSIONS:In middle-aged and older adults, plasma concentrations of kynurenine metabolites are strongly associated with adiposity, both cross-sectionally and longitudinally. Our study demonstrates that kynurenine metabolites may be valuable markers to monitor the adverse consequences of obesity.