Hormonal
Long-acting GLP-1 receptor agonists (GLP-1RAs) attenuate obesity and reverse leptin resistance by reshaping gut microbiota to increase Akkermansia muciniphila, which produces inosine to activate the macrophage A2A pathway, thereby reducing adipocyte leptin levels.
This research suggests that GLP-1 medications (like semaglutide or liraglutide) may work partly by changing your gut bacteria to produce a molecule called inosine. This molecule helps reduce leptin, a hormone that regulates fat storage. While you cannot directly control this pathway, maintaining gut health through diet may support the effectiveness of these medications.
We found that (Ex-4)2-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am)... Am enhanced (Ex-4)2-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes
Why this rating
Animal study (mice) with mechanistic depth but no human clinical data.
Source
GLP-1RAs attenuated obesity and reversed leptin resistance partly via activating the microbiome-derived inosine/A2A pathway
Chunyan Dong et al. · Acta Pharmaceutica Sinica B · 2024
DOI 10.1016/j.apsb.2024.12.006
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