Brown adipose tissue and regulation of human body weight

Abstract

Background: Approximately 30% of the global population is affected by obesity. Traditional non-surgical measures for weight loss have limited efficacy and tolerability. Therefore, there is a need for novel, effective therapies. Brown adipose tissue (BAT) has been implicated in physiological energy expenditure, indicating that it could be targeted to achieve weight loss in humans. The use of ¹⁸ F-fluorodeoxyglucose (¹⁸ F-FDG) positron emission tomography-computed tomography-(PET-CT) imaging has enabled the discovery of functionally active BAT in the supraclavicular, subclavian, and thoracic spine regions of human adults. This review aims to discuss the reasons behind the renewed interest in BAT, assess whether it is metabolically important in humans, and evaluate its feasibility as a therapeutic target for treating obesity.

Sources of material: PubMed Central, Europe PMC, Medline.

Findings: In vivo studies have shown that BAT activity is regulated by thyroid hormones and the sympathetic nervous system. Furthermore, BAT uniquely contains uncoupling protein 1 (UCP1) that is largely responsible for non-shivering thermogenesis. Cold exposure can increase BAT recruitment through the browning of white adipose tissue (WAT); however, this technique has practical limitations that may preclude its use. Currently available medicines for humans, such as the β3-adrenergic receptor agonist mirabegron or the farnesoid X receptor agonist obeticholic acid, have generated excitement, although adverse effects are a concern. Capsinoids represent a tolerable alternative, which require further investigation.

Conclusions: The use of currently available BAT-activating agents alone is unlikely to achieve significant weight loss in humans. A combination of BAT activation with physical exercise and modern, successful dietary strategies represents a more realistic option.

Keywords: brown adipose tissue (BAT); capsaicin; capsinoids; cold activation; energy expenditure; farnesoid X receptor; mirabegron; obesity; thermogenesis.