Abstract:We evaluated serum total bilirubin levels as a predictor for metabolic syndrome
(MetS) and investigated the relationship between serum total bilirubin levels and
MetS prevalence. This cross-sectional study included 1728 participants over 65 years
of age from Eastern China. Anthropometric data, lifestyle information, and previous
medical history were collected. We then measured serum levels of fasting
blood-glucose, total cholesterol, triglycerides, and total bilirubin, as well as
alanine aminotransferase activ… Show more
“…We also found that Mttp levels were low in Ppara HepKO mice, suggesting that Mttp is regulated via PPARα (Stec et al, 2019). Previous studies have shown a negative correlation between serum total bilirubin levels and blood triglyceride levels (Zhong et al, 2017;Petelin et al, 2020). Interestingly, in obese patients with low serum total bilirubin and higher triglycerides than lean control with bariatric surgery increased plasma bilirubin by two-fold and reduced triglycerides by 50% (Bawahab et al, 2017), illustrating the potential role of bilirubin in triglyceride metabolism.…”
The inverse relationship of plasma bilirubin levels with liver fat accumulation has prompted the possibility of bilirubin as a therapeutic for non-alcoholic fatty liver disease. Here, we used diet-induced obese mice with non-alcoholic fatty liver disease treated with pegylated bilirubin (bilirubin nanoparticles) or vehicle control to determine the impact on hepatic lipid accumulation. The bilirubin nanoparticles significantly reduced hepatic fat, triglyceride accumulation, de novo lipogenesis, and serum levels of liver dysfunction marker aspartate transaminase and ApoB100 containing very-low-density lipoprotein. The bilirubin nanoparticles improved liver function and activated the hepatic β-oxidation pathway by increasing PPARα and acyl-coenzyme A oxidase 1. The bilirubin nanoparticles also significantly elevated plasma levels of the ketone β-hydroxybutyrate and lowered liver fat accumulation. This study demonstrates that bilirubin nanoparticles induce hepatic fat utilization, raise plasma ketones, and reduce hepatic steatosis, opening new therapeutic avenues for NAFLD.
“…We also found that Mttp levels were low in Ppara HepKO mice, suggesting that Mttp is regulated via PPARα (Stec et al, 2019). Previous studies have shown a negative correlation between serum total bilirubin levels and blood triglyceride levels (Zhong et al, 2017;Petelin et al, 2020). Interestingly, in obese patients with low serum total bilirubin and higher triglycerides than lean control with bariatric surgery increased plasma bilirubin by two-fold and reduced triglycerides by 50% (Bawahab et al, 2017), illustrating the potential role of bilirubin in triglyceride metabolism.…”
The inverse relationship of plasma bilirubin levels with liver fat accumulation has prompted the possibility of bilirubin as a therapeutic for non-alcoholic fatty liver disease. Here, we used diet-induced obese mice with non-alcoholic fatty liver disease treated with pegylated bilirubin (bilirubin nanoparticles) or vehicle control to determine the impact on hepatic lipid accumulation. The bilirubin nanoparticles significantly reduced hepatic fat, triglyceride accumulation, de novo lipogenesis, and serum levels of liver dysfunction marker aspartate transaminase and ApoB100 containing very-low-density lipoprotein. The bilirubin nanoparticles improved liver function and activated the hepatic β-oxidation pathway by increasing PPARα and acyl-coenzyme A oxidase 1. The bilirubin nanoparticles also significantly elevated plasma levels of the ketone β-hydroxybutyrate and lowered liver fat accumulation. This study demonstrates that bilirubin nanoparticles induce hepatic fat utilization, raise plasma ketones, and reduce hepatic steatosis, opening new therapeutic avenues for NAFLD.
“…Several cross-sectional and longitudinal studies have reported an inverse association between serum TBil and MetS [ 10 , 11 , 14 , 21 ]. For example, a recent cross-sectional study involving 12342 adults in Korean suggested that elevated serum TBil was associated with a decreased risk of MetS [ 10 ].…”
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.
“…Previous studies have reported many related risk factors associated with the incidence of MetS [7][8][9], such as uric acid (UA), γ-glutamyl transpeptidase (GGT), and alanine aminotransferase (ALT). However, there are few studies grouping these factors to develop a model and predict the risk of MetS.…”
Although several risk factors for metabolic syndrome (MetS) have been reported, there are few clinical scores that predict its incidence. Therefore, we created and validated a risk score for prediction of 3-year risk for MetS. Three-year follow-up data of 4395 initially MetS-free subjects, enrolled for an annual physical examination from Wenzhou Medical Center were analyzed. Subjects at enrollment were randomly divided into the training and the validation cohort. Univariate and multivariate logistic regression models were employed for model development. The selected variables were assigned an integer or half-integer risk score proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. The predictive performance of the model was tested by computing the area under the receiver operating characteristic curve (AUROC). Four independent predictors were chosen to construct the MetS risk score, including BMI (HR=1.906, 95% CI: 1.040-1.155), FPG (HR=1.507, 95% CI: 1.305-1.741), DBP (HR=1.061, 95% CI: 1.002-1.031), HDL-C (HR=0.539, 95% CI: 0.303-0.959). The model was created as -1.5 to 4 points, which demonstrated a considerable discrimination both in the training cohort (AUROC=0.674) and validation cohort (AUROC=0.690). Comparison of the observed with the estimated incidence of MetS revealed satisfactory precision. We developed and validated the MetS risk score with 4 risk factors to predict 3-year risk of MetS, useful for assessing the individual risk for MetS in medical practice.
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