ArticleNature communications2026
ALKBH5-mediated microglia-neuron crosstalk inhibits sympathetic innervation and adipocyte browning in male mice.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Interactions between nervous system and adipose tissue are involved in the regulation of adipocyte browning. However, whether microglial activation participates in the regulation of cold exposure-induced sympathetic innervation and adipocyte browning is unclear. Here, we demonstrate that RNA m6A demethylase ALKBH5 in the microglia nucleus of hypothalamus (PVH) region inhibits cold exposure-induced adipocyte browning in the subcutaneous white adipose tissue (sWAT) of male mice. The single nuclear-RNA sequencing, brain slice electrophysiological assay and pathological analyses show that microglia-specific ALKBH5 knockout (MCKO) enhances sympathetic activation and adipocyte browning in the sWAT during cold exposure. Mechanistically, MCKO enhances m6A methylation of Ntf5 mRNA and upregulates Ntf5 expression in the microglia. Ntf5 then activates PVH-TrkB neurons and downstream sympathetic innervation in the sWAT. During aging, MCKO prevents brown adipocyte decline in the sWAT, and promotes metabolic activity. These findings fill a gap in the research of microglia in neuron-mediated adipocyte browning, and suggest that microglia may be a potential therapeutic target for the treatment of individuals with metabolic disorders.
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