Thermogenic Mechanisms in Adipose Tissue Function
Summary
Adipose tissue contributes to whole-body energy balance not only through lipid storage but also by actively generating heat. In brown adipose tissue (BAT), densely packed mitochondria express uncoupling protein 1 (UCP1), which short-circuits oxidative phosphorylation, dissipating the proton motive force as heat in a process known as non-shivering thermogenesis. White adipose tissue (WAT), long viewed as a passive energy reservoir, can acquire thermogenic capacity by recruiting beige adipocytes—cells that share BAT’s mitochondrial machinery and UCP1 expression. This plasticity is governed by hormonal, neural and local signals: catecholamines acting via β-adrenergic receptors trigger lipolysis and mitochondrial biogenesis; endocrine factors such as leptin and fibroblast growth factors modulate differentiation and UCP1 transcription; and environmental stimuli (cold exposure, exercise, dietary components) further tune the thermogenic programme. Together, these pathways underlie adaptive responses to temperature challenges and offer therapeutic avenues for metabolic disease by harnessing or mimicking physiological heat production in adipose depots.
Research from Nature Portfolio
Recent studies have identified fibroblast growth factors 6 and 9 (FGF6/FGF9) as potent adipokines that upregulate UCP1 independently of the classic adipogenic programme. These FGFs signal through FGFR3 and engage prostaglandin E2 and a transcriptional complex involving estrogen-related receptor-α, flightless-1 and FLII-interacting protein-1 to drive UCP1 gene expression. Exercise and cold exposure increase FGF6/9 levels in murine adipose, and administration of FGF9 in vivo augments BAT thermogenic capacity, highlighting a pathway that dissociates UCP1 activation from lineage commitment and may be exploited to enhance energy expenditure.
Thermogenic Mechanisms in Adipose Tissue Function publication trend
The graph below shows the total number of articles in thermogenic mechanisms in adipose tissue function across all publications each year (not limited to Nature Index journals).
Technical terms
Brown adipose tissue (BAT): A specialised fat depot rich in mitochondria that dissipates energy as heat via UCP1.
Beige adipocytes: Thermogenically active cells recruited within white fat depots that express UCP1.
Uncoupling protein 1 (UCP1): Mitochondrial inner‐membrane protein that uncouples respiration from ATP synthesis to generate heat.
Non-shivering thermogenesis: Heat production by mitochondrial uncoupling independent of muscle activity.
β3-Adrenergic receptor (ADRB3): Receptor mediating catecholamine-induced activation of lipolysis and thermogenic gene programmes in adipocytes.
Fibroblast growth factors (FGF6/FGF9): Secreted proteins acting as adipokines to regulate UCP1 transcription via FGFR3‐dependent signalling.
References
- FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis. Nature Communications (2020).
- The Role of β3-Adrenergic Receptors in Cold-Induced Beige Adipocyte Production in Pigs. Cells (2024).
- Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway. Biology (2024).
- Leptin deficiency impairs adipogenesis and browning response in mouse mesenchymal progenitors. European Journal of Cell Biology (2023).
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