Recent epidemiological and clinical data show protection from CVD (cardiovascular disease), all-cause mortality and cancer in subjects with GS (Gilbert's syndrome), which is characterized by a mildly elevated blood bilirubin concentration. The established antioxidant effect of bilirubin, however, contributes only in part to this protection. Therefore we investigated whether mildly elevated circulating UCB (unconjugated bilirubin) is associated with altered lipid metabolism. The study was performed on GS and age- and gender-matched healthy subjects ( n =59 per group). Full lipoprotein profile, TAG (triacylglycerols), Apo (apolipoprotein)-A1, Apo-B, lipoprotein(a), the subfractions of LDL (low-density lipoprotein) and selected pro-inflammatory mediators were analysed. A hyperbilirubinaemic rodent model (Gunn rats, n =40) was investigated to further support the presented human data. GS subjects had significantly ( P <0.05) improved lipid profile with reduced total cholesterol, LDL-C (LDL-cholesterol), TAG, low- and pro-atherogenic LDL subfractions (LDL-1+LDL-2), Apo-B, Apo-B/Apo-A1 ratio and lower IL-6 (interleukin 6) and SAA (serum amyloid A) concentrations ( P =0.094). When the control and GS groups were subdivided into younger and older cohorts, older GS subjects demonstrated reduced lipid variables (total cholesterol and LDL-C, TAG and LDL-C subfractions, Apo-B/Apo-A1 ratio; P <0.05; Apo-B: P <0.1) compared with controls. These data were supported by lipid analyses in the rodent model showing that Gunn rat serum had lower total cholesterol (2.29±0.38 compared with 1.27±0.72 mM; P <0.001) and TAG (1.66±0.67 compared with 0.99±0.52 mM; P <0.001) concentrations compared with controls. These findings indicate that the altered lipid profile and the reduced pro-inflammatory status in hyperbilirubinaemic subjects, particularly in the older individuals, probably contribute additionally to the commonly accepted beneficial antioxidant effects of bilirubin in humans.

Blockade of the MR (mineralocorticoid receptor) in CKD (chronic kidney disease) reduces LVMI [LV (left ventricular) mass index] and proteinuria. The MR can be activated by aldosterone, cortisol and DOC (deoxycorticosterone). The aim of the present study was to explore the influence of mineralocorticoids on LVMI and proteinuria in patients with CKD. A total of 70 patients with CKD and 30 patients with EH (essential hypertension) were recruited. Patients underwent clinical phenotyping; biochemical assessment and 24 h urinary collection for THAldo (tetrahydroaldosterone), THDOC (tetrahydrodeoxycorticosterone), cortisol metabolites (measured using GC–MS), and urinary electrolytes and protein [QP (proteinuira quantification)]. LVMI was measured using CMRI (cardiac magnetic resonance imaging). Factors that correlated significantly with LVMI and proteinuria were entered into linear regression models. In patients with CKD, significant predictors of LVMI were male gender, SBP (systolic blood pressure), QP, and THAldo and THDOC excretion. Significant independent predictors on multivariate analysis were THDOC excretion, SBP and male gender. In EH, no association was seen between THAldo or THDOC and LVMI; plasma aldosterone concentration was the only significant independent predictor. Significant univariate determinants of proteinuria in patients with CKD were THAldo, THDOC, USod (urinary sodium) and SBP. Only THAldo excretion and SBP were significant multivariate determinants. Using CMRI to determine LVMI we have demonstrated that THDOC is a novel independent predictor of LVMI in patients with CKD, differing from patients with EH. Twenty-four hour THAldo excretion is an independent determinant of proteinuria in patients with CKD. These findings emphasize the importance of MR activation in the pathogenesis of the adverse clinical phenotype in CKD.

Regular exercise can reduce the risk of CVD (cardiovascular disease). Although moderate-intensity exercise can attenuate postprandial TAG (triacylglycerol), high-intensity intermittent exercise might be a more effective method to improve health. We compared the effects of high-intensity intermittent exercise and 30 min of brisk walking on postprandial TAG, soluble adhesion molecules and markers of oxidative stress. Nine men each completed three 2-day trials. On day 1, subjects rested (control), walked briskly for 30 min (walking) or performed 5×30 s maximal sprints (high-intensity). On day 2, subjects consumed a high-fat meal for breakfast and 3 h later for lunch. Blood samples were taken at various times and analysed for TAG, glucose, insulin, ICAM-1 (intracellular adhesion molecule-1), VCAM-1 (vascular adhesion molecule-1), TBARS (thiobarbituric acid- reactive substances), protein carbonyls and β-hydroxybutyrate. On day 2 of the high-intensity trial, there was a lower ( P <0.05) incremental TAG AUC (area under the curve; 6.42±2.24 mmol/l per 7 h) compared with the control trial (9.68±4.77 mmol/l per 7 h) with no differences during day 2 of the walking trial (8.98±2.84 mmol/l per 7 h). A trend ( P =0.056) for a reduced total TAG AUC was also seen during the high-intensity trial (14.13±2.83 mmol/l per 7 h) compared with control (17.18±3.92 mmol/l per 7 h), walking showed no difference (16.33±3.51 mmol/l per 7 h). On day 2 of the high-intensity trial plasma TBARS and protein carbonyls were also reduced ( P <0.05) when compared with the control and walking trials. In conclusion, high-intensity intermittent exercise attenuates postprandial TAG and markers of oxidative stress after the consumption of a high-fat meal.