Abstract
Obesity is a chronic condition involving low-grade inflammation and increased oxidative stress; thus, obese and overweight people have lower values of serum bilirubin. Essentially, bilirubin is a potent endogenous antioxidant molecule with anti-inflammatory, immunomodulatory, antithrombotic, and endocrine properties. This review paper presents the interplay between obesity-related pathological processes and bilirubin, with a focus on adipose tissue and adipokines. We discuss potential strategies to mildly increase serum bilirubin levels in obese patients as an adjunctive therapeutic approach.
Highlights
Bilirubin, the end product of heme metabolism, is a potent endogenous antioxidant with anti-inflammatory, immunomodulatory, antithrombotic, and endocrine properties [1–3].Serum bilirubin concentrations depend on the complex interactions between bilirubin production, consumption, metabolism, and elimination
Obesity and overweight are considered pathological states of chronic low-grade inflammation with increased oxidative stress and altered endocrine signaling; these conditions result in lowered serum bilirubin levels [6]; on the other hand, reducing body weight leads to increased serum bilirubin levels [7,8]
Bilirubin acts as a ligand transactivator of constitutive androsterone receptor (CAR) and PXR to increase the expression of target genes responsible for its disposal [81], and to increase the expression of genes involved in energy metabolism [82]
Summary
The end product of heme metabolism, is a potent endogenous antioxidant with anti-inflammatory, immunomodulatory, antithrombotic, and endocrine properties [1–3]. Serum bilirubin concentrations depend on the complex interactions between bilirubin production, consumption (depending on oxidative stress and inflammation), metabolism, and elimination. Numerous studies have shown that serum bilirubin levels are inversely associated with obesity, metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and other oxidative-stress-mediated diseases, including atherosclerosis [2,4,5]. Serum bilirubin levels were recently proposed as a potential predisease biomarker for developing metabolic syndrome in asymptomatic middle-aged individuals [6]. Obesity and overweight are considered pathological states of chronic low-grade inflammation with increased oxidative stress and altered endocrine signaling; these conditions result in lowered serum bilirubin levels [6]; on the other hand, reducing body weight leads to increased serum bilirubin levels [7,8]. Mild hyperbilirubinemia is associated with health benefits in overweight and obese individuals, as well as with lower adiposity [9,10]. This review addresses the current knowledge on how overweight and obesity affect bilirubin levels, along with the potential intervention strategies to modulate systemic bilirubin levels to alleviate the obesity-related negative effects on health
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