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Transcriptome and Mass‐Spectrometry‐Based Lipidome Reveal a Role of PRMT5 in Membrane Transport and Cholesterol Synthesis in White Adipocytes
Author(s) -
Chen Xiyue,
Jia Zhihao,
Fang Shuyi,
Yue Feng,
Ferreria Christina R.,
Wan Jun,
Kuang Shihuan
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.l6381
Subject(s) - protein arginine methyltransferase 5 , lipidome , biochemistry , lipid metabolism , glycolysis , biology , chemistry , transcriptome , microbiology and biotechnology , fatty acid metabolism , fatty acid , metabolism , methyltransferase , gene expression , methylation , gene
Adipose tissue (AT) regulates systemic energy homeostasis, and its dysfunction can result in insulin resistance and other metabolic complications. Protein arginine methyltransferase 5 (PRMT5) catalyzes symmetrical demethylation of arginine residues to modulate protein stability and/or function. Besides its well‐studied oncogenic functions, PRMT5 has recently been shown to play a physiological role in AT through poorly understood mechanisms. Here, we combine RNA sequencing and mass‐spectrometry‐based lipidomic analyses of wildtype and Prmt5 knockout (Prmt5 AKO ) AT to uncover the molecular mechanisms underlying PRMT5 function. We found that Prmt5 AKO alters expression of genes related to metabolism and membrane transport. Specifically, Prmt5 AKO induces genes enriched in glucose transport and glycolysis pathways, and suppresses genes encoding fatty acid (FA) transporters. This is accompanied by changes in lipid compositions of TAGs, FAs, and phospholipids. The data indicate that Prmt5 AKO disrupts fatty acid metabolism while promoting glucose uptake and glycolysis. Prmt5 AKO also promotes cholesterol biogenesis, contributing to hyperlipidemia and hepatic steatosis in mice. The omics data together reveal a previously unappreciated role of PRMT5 in membrane transport that affects glucose metabolism and cholesterol synthesis.