title: Identification of Palmitoleic Acid Controlled by mTOR Signaling as a Biomarker of Polymyositis.
abstract: Polymyositis (PM) is a chronic disease characterized by muscle pain, weakness, and increase in muscle-related enzymes, accompanied with inflammations in lymphocytes. However, it is not well understood how the molecular alternations in lymphocytes contribute to the development of polymyositis. The mechanistic target of rapamycin (mTOR) signaling is the central regulator of metabolism and inflammation in mammalian cells. Based on previous studies, we proposed that mTOR signaling may control inflammatory reactionsvialipid metabolism. In this study, we aim to figure out the role of mTOR signaling in the development of polymyositis and identify novel biomarkers for the detection and therapy of polymyositis. After screening and validation, we found that palmitoleic acid, a monounsaturated fatty acid, is highly regulated by mTOR signaling. Inhibition of mTORC1 activity decreases palmitoleic acid level. Moreover, mTORC1 regulates the level of palmitoleic acid by controlling its de novo synthesis. Importantly, increased palmitoleic acid has been proven to be a marker of polymyositis. Our work identifies palmitoleic acid in peripheral blood mononuclear cells (PBMC) as a biomarker of polymyositis and offers new targets to the clinical therapy.
authors.affiliation: Department of General Medicine, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Geng
authors.identifier: 0000-0002-1336-9072
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Cen
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Qi-Bing
authors.identifier: 0000-0001-6830-8026
authors.initials: QB
authors.lastname: Xie
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D002478:Cells, Cultured; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects; D058990:Molecular Targeted Therapy; D017285:Polymyositis / Q000175:diagnosis*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D005229:Fatty Acids, Monounsaturated; C008757:palmitoleic acid; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus