Milestone Discovery: AMP Acts as an Epigenetic Switch to Precisely Drive White Fat Breakdown

In the fields of nutritional science and metabolic disease research, a landmark study published in Advanced Science has uncovered the in‑depth molecular mechanism by which adenosine monophosphate (AMP) regulates fat metabolism and exerts anti‑obesity effects. Led by Prof. Chengquan Tan’s team at South China Agricultural University, this research is the first to delineate the molecular pathway through which AMP precisely drives white fat breakdown via epigenetic modification (reducing DNA methylation), providing a solid theoretical foundation for the development of novel functional foods and anti‑obesity drugs.

Mechanistic studies show that AMP is converted to adenosine (ADO) by the ectoenzyme CD73, which in turn specifically activates the adenosine receptor ADORA2A signaling pathway. This cascade markedly lowers DNA methylation at the promoter region of hormone‑sensitive lipase (HSL) in white adipose tissue, thereby releasing gene silencing, promoting HSL transcription and expression, and ultimately accelerating lipolysis and improving glycolipid metabolism. Critically, the anti‑obesity effect of AMP was largely abolished in ADORA2A‑knockout mice, providing definitive reverse validation of the central regulatory role of this signaling axis.

This breakthrough not only clarifies how AMP acts as an upstream signaling molecule to govern fat metabolism but also, for the first time, tightly links nucleotide nutritional intervention with epigenetic modification (DNA demethylation). For the functional food and biopharmaceutical industries, targeting the CD73‑ADORA2A‑HSL axis has emerged as a highly promising new strategy against obesity and related metabolic syndromes, signaling a new wave of innovation in the application of nucleotide ingredients for metabolic health.

FOR DETAIL：https://doi.org/10.1002/advs.202405079

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