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.

FIGURE 1

Thermogenesis in the mitochondria of brown adipose tissue. Increased sympathetic activity and β3‐adrenoceptor stimulation drives a cAMP‐dependent mechanism, resulting in glucose uptake and lipolysis of intracellular triglycerides. Thyroxine receptor stimulation enhances the effects of increased sympathetic activity. Fatty acids and glucose are utilised in the electron transport chain and activate UCP1, which uncouples the respiratory chain from the ATP synthesis by providing an alternative route for the passage of H⁺. The flow of H⁺ through UCP1 generates heat via non‐shivering thermogenesis. Created with BioRender.com. ADP, adenosine diphosphate; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; e⁻, electron; FADH₂, reduced flavin adenine dinucleotide; H⁺, proton; NADH, reduced nicotinamide adenine dinucleotide; UCP1, uncoupling protein 1

FIGURE 2

Beiging of white adipose tissue. Cold exposure and β3‐adrenoceptor agonism converts white adipocytes into stimulated beige adipocytes, which contain UCP1‐positive mitochondria. Beige adipocytes can undergo thermogenesis via UCP1‐dependent and UCP1‐independent mechanisms. Created with BioRender.com. Ca²⁺, calcium ion; UCP1, uncoupling protein 1