Key result
Febuxostat suppresses ROS production and visceral inflammation, improving insulin sensitivity and prothrombotic tendency in mice.
Why the study?
Chronic stress is linked to metabolic syndrome, diabetes, hyperuricemia, and thromboembolism, but the underlying mechanisms remain elusive.
Does febuxostat improve stress-induced hyperuricemia, glucose dysmetabolism, and prothrombotic state in mice?
Does febuxostat improve stress-induced hyperuricemia, glucose dysmetabolism, and prothrombotic state in mice?
In a mouse model of restraint stress, xanthine oxidase inhibition with febuxostat attenuated stress-induced hyperuricemia, insulin resistance, and prothrombotic state.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating in stressed mice; human trials needed before considering febuxostat for metabolic or thrombotic risk.
Chronic stress is closely linked to the metabolic syndrome, diabetes, hyperuricemia and thromboembolism, but the mechanisms remain elusive. We reported recently that stress targets visceral adipose tissue (VAT), inducing lipolysis, low-grade inflammation with production of inflammatory adipokines, metabolic derangements such as insulin resistance, and prothrombotic state. In the present study, we hypothesized the involvement of VAT xanthine oxidoreductase (XOR), a source of reactive oxygen species (ROS) and uric acid (UA) in the above processes. Restraint stress in mice resulted in upregulation of XOR and xanthine oxidase activity, accumulation of ROS in VAT as well as liver and intestine, increase in serum UA levels, upregulation of NADPH oxidase subunits and downregulation of antioxidant enzymes. Immunohistochemistry and RT-PCR analysis also showed that restraint stress induced VAT monocyte accumulation and proinflammatory adipokine production, resulting in reduced insulin sensitivity and induction of plasminogen activator inhibitor-1 and tissue factor in VAT. Treatment with febuxostat, a potent XO inhibitor, suppressed stress-induced ROS production and VAT inflammation, resulting in improvement of serum UA levels, insulin sensitivity, and prothrombotic tendency. Our results suggest that stress perturbs glucose and UA metabolism, and promotes prothrombotic status, and that XO inhibition by febuxostat might be a potential therapy for stress-related disorders.
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Yisireyili et al. (2017) studied Stress-induced hyperuricemia, glucose dysmetabolism, and prothrombotic state (n=41). Febuxostat vs. Vehicle (0.4% methylcellulose) was evaluated on Xanthine oxidoreductase (XOR) activity, reactive oxygen species (ROS) production, and insulin sensitivity. Febuxostat suppressed stress-induced reactive oxygen species production and visceral adipose tissue inflammation, improving serum uric acid levels, insulin sensitivity, and prothrombotic tendency in mice.
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