Brown Adipose Tissue Thermogenesis and Metabolic Health
Summary
Brown adipose tissue (BAT) is a specialised form of adipose tissue characterised by mitochondria-rich adipocytes that dissipate chemical energy as heat via uncoupling protein 1 (UCP1). Originally thought to be confined to hibernating mammals and neonates, active BAT depots have now been demonstrated in adult humans. BAT activation through cold exposure or sympathetic stimulation enhances non-shivering thermogenesis, increases whole-body energy expenditure and modulates glucose and lipid metabolism. These thermogenic responses are mediated by sympathetic noradrenaline release, which upregulates UCP1 expression and drives mitochondrial proton leak. Beyond its role in acute thermoregulation, BAT influences systemic metabolic health by clearing circulating substrates such as glucose, fatty acids and branched-chain amino acids, and by secreting adipokines that affect insulin sensitivity. Variability in BAT abundance and function across age, sex, adiposity and pharmacological treatments underlies differential metabolic outcomes. Quantitative imaging of BAT activity and temperature has advanced our understanding of its contribution to obesity, type 2 diabetes and cardiometabolic risk, positioning BAT as a potential therapeutic target for metabolic disease.
Research from Nature Portfolio
Recent studies have uncovered a human-specific regulatory mechanism in which the serotonin transporter (SERT) safeguards BAT function by preventing serotonin-mediated suppression of mitochondrial respiration and UCP1 abundance. Inhibition of SERT by selective serotonin reuptake inhibitors impairs BAT activation in healthy volunteers, suggesting a mechanistic link between antidepressant use, diminished thermogenesis and weight gain. Parallel technical advances have introduced non-invasive magnetic resonance thermometry with hyperpolarised 129Xe gas, enabling direct measurement of BAT temperature during cold exposure. This method reveals supraclavicular BAT temperatures averaging almost 39 °C, exceeding core body temperature, and offers a radiation-free approach to longitudinally track thermogenic activity. A foundational investigation into dietary fatty acid metabolism during cold acclimation has shown that BAT in humans selectively extracts circulating fatty acids, though its quantitative contribution to systemic fatty acid clearance remains modest compared with heart, liver and skeletal muscle. Together, these findings elucidate both novel regulatory pathways and innovative measurement techniques that refine our appreciation of human BAT thermogenesis.
Brown Adipose Tissue Thermogenesis and Metabolic Health publication trend
The graph below shows the total number of articles in brown adipose tissue thermogenesis and metabolic health across all publications each year (not limited to Nature Index journals).
Technical terms
Brown adipose tissue (BAT): Thermogenic fat depots containing mitochondria-rich adipocytes that dissipate chemical energy as heat.
Uncoupling protein 1 (UCP1): Mitochondrial inner-membrane protein that enables proton leak and heat generation independent of ATP synthesis.
Non-shivering thermogenesis: Heat production by metabolic processes in BAT and other tissues without muscular shivering.
Sympathetic nervous system: Branch of the autonomic nervous system that stimulates BAT via noradrenaline release.
Positron emission tomography (PET): Imaging modality using radiotracers to quantify BAT activity and substrate uptake.
Hyperpolarised xenon magnetic resonance: Non-invasive technique measuring tissue temperature by exploiting enhanced 129Xe MR signal sensitivity to temperature.
Branched-chain amino acids (BCAAs): Essential amino acids metabolised by BAT that influence systemic energy homeostasis.
Serotonin transporter (SERT): Membrane protein regulating extracellular serotonin levels and modulating BAT thermogenic function.
References
- The serotonin transporter sustains human brown adipose tissue thermogenesis. Nature Metabolism (2023).
- Absolute thermometry of human brown adipose tissue by magnetic resonance with laser polarized 129Xe. Communications Medicine (2023).
- UCP1 expression in human brown adipose tissue is inversely associated with cardiometabolic risk factors. European Journal of Endocrinology (2024).
- Brown Adipose Tissue: A New Potential Target for Glucagon-like Peptide 1 Receptor Agonists in the Treatment of Obesity. International Journal of Molecular Sciences (2023).
- The role of brown adipose tissue in branched-chain amino acid clearance in people. iScience (2024).
- Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men. Nature Communications (2017).
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