Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a growing global health issue, affecting approximately 30% of the population, with no effective pharmacological treatments currently available. The pathogenesis of MAFLD involves complex interactions between adipose tissue and the liver, with brown adipose tissue (BAT) gaining increasing attention for its role in metabolic regulation.
BAT, traditionally known for its role in thermogenesis, is now recognized for its secretory functions. Unlike white adipose tissue (WAT), which primarily stores energy, BAT is active in energy expenditure and regulates systemic metabolism through the secretion of various mediators, including proteins, lipids, and microRNAs (miRNAs). These BAT-derived factors participate in interorgan crosstalk, influencing processes such as glucose homeostasis, lipid metabolism, and insulin sensitivity. Studies have shown that activating BAT or transplanting BAT from lean individuals into obese models can significantly improve metabolic dysfunctions, including hepatic steatosis and insulin resistance.
A new study published in Life Metabolism has identified BAT-derived miR-206-3p as a key player in alleviating MAFLD. The research demonstrates that exosomal miR-206-3p, secreted by BAT, is transported to the liver, where it significantly inhibits hepatic lipogenesis (Figure 1). In obese mice, BAT-derived miR-206-3p levels are reduced in BAT, leading to increased activity of the pentose phosphate pathway (PPP) in the liver and subsequently promoting liver fat accumulation. By targeting key enzymes in the PPP, miR-206-3p reduces NADPH production, thereby inhibiting fatty acid synthesis.
This discovery not only unveils a novel mechanism by which BAT influences liver metabolism but also highlights miR-206-3p as a potential therapeutic target for treating MAFLD. Restoring miR-206-3p levels could offer a promising new approach to combat obesity-related liver diseases.
Life Metabolism
Experimental study
Human tissue samples
The brown fat-enriched exosomal miR-206-3p attenuates hepatic lipogenesis by decreasing pentose phosphate pathway
12-Jul-2025