AMPK Signaling in Adipose Tissue Metabolism

AMP-activated protein kinase (AMPK) serves as a central energy sensor in adipose tissue, orchestrating the balance between lipid storage and energy expenditure. In white adipose tissue, AMPK activation modulates lipogenesis, lipolysis and glucose uptake, whereas in brown and beige fat it promotes mitochondrial biogenesis and thermogenic gene expression. Through phosphorylation of key metabolic enzymes and transcriptional regulators, AMPK influences adipocyte differentiation, suppressing excessive lipid accumulation while fostering the emergence of thermogenically competent cells. Cross-talk with pathways such as PI3K/AKT, cAMP-PKA and PRDM16-mediated networks underlies the adaptive browning of white depots and the maintenance of brown adipose activity. Given the global burden of obesity and related disorders, targeting AMPK signalling offers a promising strategy to enhance healthy adipose expansion, improve insulin sensitivity and augment energy dissipation.

Research from Nature Portfolio

Recent studies have identified novel modulators of adipose function that intersect with AMPK-regulated processes. Inhibition of AXL receptor tyrosine kinase was shown to enhance thermogenic capacity in brown and white adipocytes by suppressing PI3K/AKT/PDE signalling, thereby increasing intracellular cAMP levels, promoting nuclear localisation of FOXO1 and activating PKA-ATF2 pathways. Another investigation revealed that pharmacological activation of the cAMP‐binding protein EPAC1 selectively expands brown adipose mass and induces beige adipogenesis via networks centred on PDGFRα-positive preadipocytes, leading to elevated energy expenditure and protection against diet-induced obesity in both rodents and human organoids. Moreover, work on apoptotic brown adipocytes demonstrated that release of the purine inosine stimulates cAMP-PKA–dependent thermogenic programmes through modulation of nucleoside transporter ENT1, highlighting a ‘replace-me’ paracrine mechanism that sustains adipose thermogenesis and counters obesity.

AMPK Signaling in Adipose Tissue Metabolism publication trend

The graph below shows the total number of articles in ampk signaling in adipose tissue metabolism across all publications each year (not limited to Nature Index journals).

Technical terms

AMP-activated protein kinase (AMPK): A serine/threonine kinase complex that senses cellular energy status and modulates metabolic pathways through phosphorylation of downstream targets.

Adipogenesis: The differentiation process by which mesenchymal precursors become mature lipid-storing adipocytes.

Browning: The induction of thermogenically active beige adipocytes within white fat depots, characterised by mitochondrial enrichment and uncoupling protein-1 expression.

Thermogenesis: The production of heat in organisms, predominantly via uncoupling protein-1 in brown and beige adipocytes.

cAMP: Cyclic adenosine monophosphate, a second messenger that activates protein kinase A and influences metabolic enzyme activity and gene expression.

PRDM16: A zinc-finger transcriptional co-regulator essential for brown and beige adipocyte development and maintenance of thermogenic programmes.

References

1. Inhibition of AXL receptor tyrosine kinase enhances brown adipose tissue functionality in mice. Nature Communications (2023).
2. EPAC1 enhances brown fat growth and beige adipogenesis. Nature Cell Biology (2024).
3. New concepts in the roles of AMPK in adipocyte stem cell biology. Essays in Biochemistry (2024).
4. Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans. Cell Death & Disease (2019).
5. Apoptotic brown adipocytes enhance energy expenditure via extracellular inosine. Nature (2022).