Protein Arginine Methyltransferase 1 Interacts With PGC1α and Modulates Thermogenic Fat Activation

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)

Protein arginine methyltransferases (PRMTs) are enzymes that regulate the evolutionarily conserved process of arginine methylation. It has been reported that PRMTs are involved in many metabolic regulatory pathways. However, until now, their roles in adipocyte function, especially browning and thermogenesis, have not been evaluated. Even though Prmt1 adipocyte-specific-deleted mice (Prmt1fl/flAQcre) appeared normal at basal level, following cold exposure or β-adrenergic stimulation, impaired induction of the thermogenic program was observed in both the interscapular brown adipose tissue and inguinal white adipose tissue of Prmt1fl/flAQcre mice compared with littermate controls. Different splicing variants of Prmt1 have been reported. Among them, PRMT1 variant 1 and PRMT1 variant 2 (PRMT1V2) are well conserved between humans and mice. Both variants contribute to the activation of thermogenic fat, with PRMT1V2 playing a more dominant role. Mechanistic studies using cultured murine and human adipocytes revealed that PRMT1V2 mediates thermogenic fat activation through PGC1α, a transcriptional coactivator that has been shown to play a key role in mitochondrial biogenesis. To our knowledge, our data are the first to demonstrate that PRMT1 plays a regulatory role in thermogenic fat function. These findings suggest that modulating PRMT1 activity may represent new avenues to regulate th

Evidence level

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

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