Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogramming.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The liver-adipose axis represents a crucial regulatory network that governs systemic lipid homeostasis, with signals originating from the liver orchestrating the plasticity of adipose tissue through diverse mechanisms. A comprehensive understanding of these bidirectional communication pathways may uncover novel therapeutic approaches for metabolic disorders. Our research demonstrates that exposure to cold stimulates the liver to secrete exosomes, which enhance thermogenic activation in adipose tissue, as observed in both in vitro and in vivo models. This enhancement of thermogenesis is mechanistically associated with the cold-induced upregulation of hepatocyte-derived exosomal miR-293-5p. Importantly, the pharmacological administration of a miR-293-5p agomir significantly mitigates diet-induced obesity and related metabolic dysfunctions in murine models. Through mechanistic analysis, we identified Tet1 as a direct downstream target of miR-293-5p, noting that the ectopic expression of Tet1 disrupts the thermogenic programming of brown adipose tissue (BAT) independently of miR-293-5p modulation. Our findings establish cold-activated hepatocyte exosomes as endocrine signaling mediators that carry thermogenic microRNA cargos, with miR-293-5p emerging as a key regulator.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.