Abstract
Exercise is commonly prescribed as a lifestyle treatment for chronic metabolic diseases as it functions as an insulin sensitizer, cardio-protectant, and essential lifestyle tool for effective weight maintenance. Exercise boosts the production of reactive oxygen species (ROS) and subsequent transient oxidative damage, which also upregulates counterbalancing endogenous antioxidants to protect from ROS-induced damage and inflammation. Exercise elevates heme oxygenase-1 (HO-1) and biliverdin reductase A (BVRA) expression as built-in protective mechanisms, which produce the most potent antioxidant, bilirubin. Together, these mitigate inflammation and adiposity. Moderately raising plasma bilirubin protects in two ways: (1) via its antioxidant capacity to reduce ROS and inflammation, and (2) its newly defined function as a hormone that activates the nuclear receptor transcription factor PPARα. It is now understood that increasing plasma bilirubin can also drive metabolic adaptions, which improve deleterious outcomes of weight gain and obesity, such as inflammation, type II diabetes, and cardiovascular diseases. The main objective of this review is to describe the function of bilirubin as an antioxidant and metabolic hormone and how the HO-1–BVRA–bilirubin–PPARα axis influences inflammation, metabolic function and interacts with exercise to improve outcomes of weight management.
Highlights
Given that heme oxygenase-1 (HO-1) expression is directly influenced by exercise training (Figure 4), it is logical to assume that exercise increases plasma bilirubin levels
While there are limited studies showing that biliverdin reductase A (BVRA) is regulated by exercise [70], there have been supporting studies showing a role for the enzyme in metabolism [50,51,124,125,127]
Reduced adipocyte levels in BVRA in obese human patients resulted in significantly more hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) [128]. These results suggest that BVRA can have both direct and indirect effects to contribute to hepatic steatosis and the development of NAFLD
Summary
Despite the continued interest in exercise training for obesity prevention and treatment. Can improve exercise training outcomes to [referred to as “exercise enhancers” (EEs)] can improve exercise training outcomes enhance athletic performance. This review review provides provides aa brief brief overview overview of of exercise exercise in in preventing preventing metabolic metabolic dysfunction dysfunction along along with with the the potential role of select antioxidants (i.e., bilirubin and others), vitamin D, and nitrates on improving metabolic outcomes associated with exercise. The primary focus will shift to describing bilirubin’s emerging significance as a potential EE due to its role as a strong antioxidant and metabolic hormone. The. The role of exercise and its influence on bilirubin catabolism will be discussed along with proposed theories on how bilirubin bilirubin may may influence influence physiological physiological adaptations adaptations associated associatedwith with exerexertheories cise training and how this might impact inflammatory responses. PPARs and their impact on exercise and inflammation will be discussed
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