Serum Bilirubin Correlates with Serum Adipokines in Normal Weight and Overweight Asymptomatic Adults

Petelin, Ana; Jurdana, Mihaela; Pražnikar, Zala Jenko; Žiberna, Lovro

doi:10.20471/acc.2020.59.01.03

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…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.…”

Section: Discussionsupporting

confidence: 65%

Bilirubin Nanoparticles Reduce Diet-Induced Hepatic Steatosis, Improve Fat Utilization, and Increase Plasma β-Hydroxybutyrate

Hinds¹,

Creeden

Gordon

et al. 2020

Front. Pharmacol.

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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.

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Section: Discussionsupporting

confidence: 65%

Bilirubin Nanoparticles Reduce Diet-Induced Hepatic Steatosis, Improve Fat Utilization, and Increase Plasma β-Hydroxybutyrate

Hinds¹,

Creeden

Gordon

et al. 2020

Front. Pharmacol.

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“…Chronic overfeeding induces adipocyte hypertrophy, and then activates inflammatory pathways and accelerates inflammatory cells’ infiltration in adipose tissue, which further promote chronic low-grade inflammation and systemic insulin resistance in diet-induced obese mice ( 15 – 17 ). A recent human study showed that serum bilirubin level was negatively associated with inflammatory cytokines such as TNF-α, IL-6 and CRP, and positively associated with anti-inflammatory adiponectin ( 18 ). Consistently, our study showed that relatively reduced inflammatory state and heightened insulin sensitivity predicted favorable metabolic parameters in MHO patients.…”

Section: Discussionmentioning

confidence: 99%

Serum Bilirubin Level Is Increased in Metabolically Healthy Obesity

Wang

Zhang

et al. 2022

Front. Endocrinol.

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ObjectivesBilirubin is a biochemical substance with metabolic benefits. The objective of this research was to elucidate the association between serum bilirubin levels and metabolic alterations in different obesity phenotypes.MethodsIn total, 1,042 drug-naive participants were included in the study. Of them, 541 were obese patients and 501 were age-matched and sex-matched healthy control subjects. The obese patients were divided into metabolically healthy obesity (MHO) group and metabolically unhealthy obesity (MUHO) group according to the levels of fasting plasma glucose (FBG), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and blood pressure (BP). Clinical and biochemical parameters including total bilirubin (TBil), indirect bilirubin (IBil) and direct bilirubin (DBil) were measured. ANOVA or Kruskal-Wallis H test was used to test differences among the three groups. Pearson and Spearman correlations were used to analyze the relationships between two parameters. The relationships between bilirubin and other variables were analyzed using Multivariate regression analysis.ResultsMHO group had favorable blood pressure, glucose and lipids profiles, along with increased TBil and DBil, and decreased high-sensitivity C-reactive protein (hsCRP) and homeostasis model assessment of insulin resistance (HOMA-IR) levels when compared to MUHO group (P < 0.05 for all). TBil and DBil were negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), hsCRP and HOMA-IR, even after adjusted for age, gender and BMI (all P <0.01). Multivariate regression analysis demonstrated that HOMA-IR was independently correlated with TBil and DBIi levels (β = -0.400, P < 0.01).ConclusionMHO group harbors increased bilirubin level compared with MUHO group. HOMA-IR was independently correlated with TBil and DBIi levels.

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“…According to the study, we found that the proinflammatory effect of GGT may be through the promotion of IL-6 levels, which leads to CRP levels rise, consumption of more complement, making the increase of GGT become a risk factor for SLE aggravation (28,29). At the same time, we also found that the anti-inflammatory effect of TBIL may be reflected by inhibiting TNF-a levels, which leads to the decrease of CRP level and decrease of complement consumption, making the decrease of TBIL a risk factor for SLE aggravation (30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 69%

Association Between Gamma-Glutamyl Transferase, Total Bilirubin and Systemic Lupus Erythematosus in Chinese Women

et al. 2021

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BackgroundSystemic lupus erythematosus (SLE) affects many organs and systems of the human organism, at present, its specific pathogenesis is not completely clear, but inflammation is considered to be an important factor involved in the pathogenesis and progression of SLE. Gamma-glutamyl transpeptidase (GGT) and total bilirubin (TBIL) have different effects on inflammation: GGT has pro-inflammatory effects, on the contrary, TBIL has anti-inflammatory effects. Study has found that GGT and TBIL play opposite roles in metabolic diseases. However, the roles of them in SLE are unknown. Meanwhile, the relationship between GGT and SLE also remains unexplored.MethodWe recruited 341 SLE patients and 332 healthy individuals in Liaocheng People’s Hospital from August 2018 to May 2019. We diagnosed SLE using 2019 revised American College of Rheumatology (ACR) SLE criteria, and modeled the study outcomes using logistic regression to explore the respective relationship between GGT, TBIL and SLE. We also analyzed the interaction of GGT and TBIL in the progression of SLE.ResultsWe found that the levels of CRP, IL-6 and TNF-α in the aggravated group were significantly higher than those in the unaggravated group, the levels of C3 and C4 in the aggravated group were significantly lower than those in the unaggravated group. According to Spearman correlation analysis, GGT is proportional to CRP (rs=0.417) and IL-6 (rs=0.412), inversely proportional to C3 (rs=-0.177) and C4 (rs=0.-132). TBIL was inversely proportional to CRP (rs=-0.328) and TNF(rs=-0.360), and positively proportional to C3 (rs=0.174) and C4 (rs=0.172). In the fully adjusted model, compared to the lowest quartile, the highest quartile of GGT exhibited a positive association with the risk of SLE aggravation (OR=2.99, 95% CI: 1.42–6.31, P<0.001). At the same time, compared to the highest quartile, the quartile lowest of TBIL exhibited a positive association with the risk of SLE aggravation (OR=2.66, 95% CI: 1.27–5.59, P<0.001) in the fully adjusted model. Through interaction analysis, we found that women with high GGT levels had an increased risk of SLE aggravation when they had a low level of TBIL (OR=3.68, 95% CI: 1.51–9.01, for women with Q1 TBIL and Q4 GGT compared to women with Q2-Q4 TBIL and Q1-Q3 GGT, P for interaction <0.001), the combined AUC value (AUCCOMBINED=0.711) of high GGT level and TBIL were higher than their respective values (AUCGGT=0.612, AUCTBIL=0.614).ConclusionWe found that the effects of GGT and TBIL in the progression of SLE are opposite. High GGT level might be a risk factor for SLE aggravation, as GGT levels increased, so did the risk of SLE aggravation. At the same time, we found that low TBIL level might be a risk factor for SLE aggravation. Moreover, high GGT level and low TBIL level had a subadditive effect on the increased risk of SLE aggravation.

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Serum Bilirubin Correlates with Serum Adipokines in Normal Weight and Overweight Asymptomatic Adults

Cited by 7 publications

References 43 publications

Bilirubin Nanoparticles Reduce Diet-Induced Hepatic Steatosis, Improve Fat Utilization, and Increase Plasma β-Hydroxybutyrate

Bilirubin Nanoparticles Reduce Diet-Induced Hepatic Steatosis, Improve Fat Utilization, and Increase Plasma β-Hydroxybutyrate

Serum Bilirubin Level Is Increased in Metabolically Healthy Obesity

Association Between Gamma-Glutamyl Transferase, Total Bilirubin and Systemic Lupus Erythematosus in Chinese Women

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