Abstract
We previously reported the involvement of protein arginine methyltransferase 1 (PRMT1) in adipocyte thermogenesis. Here, we investigate the effects of PRMT1 inhibitors on thermogenesis. Unexpectedly, we find that the PRMT1 inhibitor TC-E 5003 (TC-E) induces the thermogenic properties of primary murine and human subcutaneous adipocytes. TC-E treatment upregulates the expression of Ucp1 and Fgf21 significantly and activates protein kinase A signaling and lipolysis in primary subcutaneous adipocytes from both mouse and humans. We further find that the thermogenic effects of TC-E are independent of PRMT1 and beta-adrenergic receptors. Our data indicate that TC-E exerts strong effects on murine and human subcutaneous adipocytes by activating beige adipocytes via PKA signaling.
Keywords:
PKA; PRMT1; UCP1; lipolysis; thermogenesis.
© 2020 Federation of European Biochemical Societies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes, Beige / cytology
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Adipocytes, Beige / drug effects
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Adipocytes, Beige / enzymology
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Adipocytes, Brown / cytology
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Adipocytes, Brown / drug effects
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Adipocytes, Brown / enzymology
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Adipocytes, White / cytology
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Adipocytes, White / drug effects
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Adipocytes, White / enzymology
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Animals
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Benzeneacetamides / pharmacology*
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Cyclic AMP-Dependent Protein Kinases / genetics*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Enzyme Inhibitors / pharmacology*
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Fibroblast Growth Factors / genetics
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Fibroblast Growth Factors / metabolism
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Gene Expression Regulation
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Humans
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Lipolysis / drug effects
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Lipolysis / genetics
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Mice
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Primary Cell Culture
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Protein-Arginine N-Methyltransferases / antagonists & inhibitors
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Protein-Arginine N-Methyltransferases / genetics*
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Protein-Arginine N-Methyltransferases / metabolism
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Receptors, Adrenergic, beta / genetics
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Receptors, Adrenergic, beta / metabolism
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Repressor Proteins / antagonists & inhibitors
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Signal Transduction / drug effects*
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Thermogenesis / drug effects*
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Thermogenesis / genetics
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Uncoupling Protein 1 / genetics
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Uncoupling Protein 1 / metabolism
Substances
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Benzeneacetamides
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Enzyme Inhibitors
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FGF21 protein, human
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Receptors, Adrenergic, beta
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Repressor Proteins
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UCP1 protein, human
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Uncoupling Protein 1
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Fibroblast Growth Factors
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PRMT1 protein, human
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Protein-Arginine N-Methyltransferases
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Cyclic AMP-Dependent Protein Kinases