Direct Bilirubin Levels and Risk of Metabolic Syndrome in Healthy Chinese Men

Abstract

Background Serum bilirubin is a potent endogenous antioxidant with anti-inflammatory properties. Several cross-sectional studies have reported that bilirubin was negatively associated with metabolic syndrome. However, in recent longitudinal studies, the relations between bilirubin and metabolic syndrome are inconsistent. Moreover, previous studies mainly focused on serum total bilirubin which is the sum of direct bilirubin and indirect bilirubin. For these reasons, the longitudinal effect of bilirubin subtypes on incident metabolic syndrome was evaluated in Chinese men. Methods The study cohort involved 1339 Chinese men without metabolic syndrome. Metabolic syndrome was defined by the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) criteria, using BMI for the replacement of waist circumference. Results There are 117 incident metabolic syndrome cases (8.7%) during 5 years of follow-up among 1339 metabolic syndrome-free participants at baseline. After adjusting for age, drinking, smoking, physical activity, TG, and LDL-C, the odd ratios (ORs) and 95% confidence intervals (CIs) for MetS incidence in the second, third, and fourth quartiles versus the first quartile of DBil concentration were 1.00 (0.61–1.63), 0.57 (0.32–1.02), and 0.51 (0.28–0.92) (Ptrend = 0.031), respectively. Conclusions Our findings support the negative association between direct bilirubin and incident metabolic syndrome in healthy Chinese men over 5-year period.

Immune challenge-induced oxidative damage may be mitigated by biliverdin

“…First, we did not quantify individual food consumption prior to or during the 24 h experimental period, which could have important explanatory power regarding body mass. Second, our predictions were derived from work with humans exhibiting metabolic syndrome, which is characterized by factors such as obesity, inflammation and hypertension (Li et al, 2017;Vanella et al, 2014). These human individuals exhibit both lower levels of bilirubin (the reduced form of biliverdin; Li et al, 2017) and lower activity of HO (Vanella et al, 2014), which is why we predicted that lower levels of biliverdin might be associated with higher levels of triglyceride-associated metrics.…”

“…Second, our predictions were derived from work with humans exhibiting metabolic syndrome, which is characterized by factors such as obesity, inflammation and hypertension (Li et al, 2017;Vanella et al, 2014). These human individuals exhibit both lower levels of bilirubin (the reduced form of biliverdin; Li et al, 2017) and lower activity of HO (Vanella et al, 2014), which is why we predicted that lower levels of biliverdin might be associated with higher levels of triglyceride-associated metrics. However, metabolic syndrome is also associated with overweight individuals circulating higher levels of triglycerides (Wu et al, 2011), and because we found that the largest birds did not have significantly higher levels of circulating triglycerides, humans exhibiting metabolic syndrome may not be an appropriate group from which to generate predictions between body mass and circulating biliverdin levels.…”

“…First, the metabolic syndrome literature is with regard to mean body mass (e.g. Li et al, 2017), not change in body mass over a short time frame, including time periods that are shorter or longer than 24 h. Second, many of the associations between bilirubin and body mass are linked to triglyceride levels (Cho et al, 2016), yet our results demonstrate that while change in body mass is related to both triglyceride and biliverdin levels, triglyceride concentration does not directly correlate with biliverdin concentration in either the liver or plasma. Thus, it is likely that some other physiological pathway is the causal mechanism driving change in body mass, HO expression (and therefore biliverdin levels) and triglyceride mobilization or transport.…”

“…Additionally, there are several links between the reduced form of biliverdin (i.e. bilirubin) and aspects of metabolism in humans, including negative correlations between bilirubin levels and the diagnosis of metabolic syndrome (a phenotype associated with obesity; Li et al, 2017) or hypertriglyceridemia (Wu et al, 2011). Thus, if immune challenges affect circulating triglyceride levels, then biliverdin concentration may also change proportionally via an unidentified mechanism.…”

“…Regardless of treatment, if biliverdin is acting as an antioxidant in vivo, then we predict a negative correlation between oxidative damage and biliverdin concentration as increases in oxidative damage decrease biliverdin concentration. Lastly, if biliverdin has similar associations with triglyceride levels in birds to those of bilirubin in mammals (Wu et al, 2011;Li et al, 2017), then biliverdin concentration in tissues should be negatively correlated with factors such as circulating triglyceride levels and body mass.…”