Bilirubin Levels Are Negatively Correlated with Adiposity in Obese Men and Women, and Its Catabolized Product, Urobilin, Is Positively Associated with Insulin Resistance

Abstract

Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein. We hypothesized that when bilirubin levels are decreased, the urobilin increases in the plasma of obese humans, as compared to lean humans. To test this, we measured plasma levels of bilirubin and urobilin, body mass index (BMI), adiposity, blood glucose and insulin, and HOMA IR in a small cohort of obese and lean men and women. We found that bilirubin levels negatively correlated with BMI and adiposity in obese men and women, as compared to their lean counterparts. Contrarily, urobilin levels were positively associated with adiposity and BMI. Only obese women were found to be insulin resistant based on significantly higher HOMA IR, as compared to lean women. The urobilin levels were positively associated with HOMA IR in both groups, but women had a stronger linear correlation. These studies indicate that plasma urobilin levels are associated with obesity and its comorbidities, such as insulin resistance.

Keywords: BMI; BVRA; HO-1; HOMA IR; UGT1A1; bilirubin; blood glucose; insulin resistance; obesity; urobilin.

Figure 1

The relationship between urobilin and total bilirubin levels in women and men. Pearson’s coefficient comparisons in all samples from men and women to determine the slope of the line and the relationship between urobilin and bilirubin in lean participants of both sexes (A), only women (B) or only men (C). The data were plotted as dot plots, linear regression was calculated, and the slope of the line was used to determine the relationship and the robustness of the data. Light gray squares are for lean women and men combined, and dark gray circles are for obese men and women combined. Red circles are for obese women, blue circles are for obese men, and gray circles are for their lean counterparts.

Figure 2

Urobilin levels and correlations with metabolic phenotypes in women and men. Comparisons of metabolic phenotypes in women and men with plasma urobilin levels for (A) BMI, (B) body fat percentage, (C) blood glucose, (D) blood insulin, and (E) HOMA IR. The data were plotted as dot plots, linear regression was calculated, and the slope of the line was used to determine the relationship and the robustness of the data. Light gray squares are for lean women and men combined, and dark gray circles are for obese men and women combined.

Figure 3

Urobilin levels and correlations with metabolic phenotypes in women. Comparisons of metabolic phenotypes in women with plasma urobilin levels for (A) BMI, (B) body fat percentage, (C) blood glucose, (D) blood insulin, and (E) HOMA IR. The data were plotted as dot plots, linear regression was calculated, and the slope of the line was used to determine the relationship and the robustness of the data. Red circles are for obese women, and gray circles are for their lean counterparts.

Figure 4

Urobilin levels and correlations with metabolic phenotypes in men. Comparisons of metabolic phenotypes in men with plasma urobilin levels for (A) BMI, (B) body fat percentage, (C) blood glucose, (D) blood insulin, and (E) HOMA IR. The data were plotted as dot plots, linear regression was calculated, and the slope of the line was used to determine the relationship and the robustness of the data. Blue circles are for obese men, and gray circles are for their lean counterparts.

Figure 5

Bilirubin levels and correlations with metabolic phenotypes in women and men. Comparisons of metabolic phenotypes in women and men with plasma bilirubin levels for (A) BMI, (B) body fat percentage, (C) blood glucose, (D) blood insulin, and (E) HOMA IR. The data were plotted as dot plots, linear regression was calculated, and the slope of the line was used to determine the relationship and the robustness of the data. Light gray squares are for lean women and men combined, and dark gray circles are for obese men and women combined.

Figure 6

Bilirubin levels and correlations with metabolic phenotypes in women. Comparisons of metabolic phenotypes in women with plasma bilirubin levels for (A) BMI, (B) body fat percentage, (C) blood glucose, (D) blood insulin, and (E) HOMA IR. The data were plotted as dot plots, linear regression was calculated, and the slope of the line was used to determine the relationship and the robustness of the data. Red circles are for obese women, and gray circles are for their lean counterparts.

Figure 7

Bilirubin levels and correlations with metabolic phenotypes in men. Comparisons of metabolic phenotypes in men with plasma bilirubin levels for (A) BMI, (B) body fat percentage, (C) blood glucose, (D) blood insulin, and (E) HOMA IR. The data were plotted as dot plots, linear regression was calculated, and the slope of the line was used to determine the relationship and the robustness of the data. Blue circles are for obese men, and gray circles are for their lean counterparts.

Figure 8

Urobilin and bilirubin levels in obesity. Bilirubin is conjugated in the liver and then catabolized in the intestine to form urobilin by the gut microbiome, which can be absorbed via the hepatic portal vein. The plasma levels of urobilin are positively associated with adiposity and BMI and might be a regulator of insulin resistance. Bilirubin is negatively associated with adiposity and BMI.