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

First Author  Qiao X Year  2019
Journal  Endocrinology Volume  160
Issue  12 Pages  2773-2786
PubMed ID  31555811 Mgi Jnum  J:283768
Mgi Id  MGI:6376896 Doi  10.1210/en.2019-00504
Citation  Qiao X, et al. (2019) Protein Arginine Methyltransferase 1 Interacts With PGC1alpha and Modulates Thermogenic Fat Activation. Endocrinology 160(12):2773-2786
abstractText  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 beta-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 PGC1alpha, 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 thermogenic fat and mediate energy homeostasis. This function is conserved in human primary adipocytes, suggesting that further investigation of this pathway may ultimately lead to therapeutic strategies against human obesity and associated metabolic disorders.
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