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Different lipids remodeling signature demonstrated heterogeneity of white adipose tissue browning

中国药理学与毒理学杂志 2019年第10期 921-921页

作者： HE Ping HOU Bi-yu YANG Xiu-ying ZHANG Li QIANG Gui-fen DU Guan-hua State Key Laboratory of Bioactive Substance and Function of Natural Medicines and Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College

OBJECTIVE White adipose tissue(WAT)browning confers beneficial effects on metabolic ***, visceral adipose tissue(VAT) is not as susceptible to browning as subcutaneousadipose tissue(SAT).Therefore, interpreting the heterogeneity of VAT and SAT in brown remodeling is extremely important. METHODS We first investigated the effects of beta-3 adrenergic stimulation by CL316, 243 on systemic metabolism. Then, highcoverage targeted lipidomics approach with multiple reaction monitoring(MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT using an Exion ultra performance liquid chromatography(UPLC)coupled with Sciex QTRAP 6500 Plus. RESULTS Beta-3 adrenergic stimulation notably ameliorated the systemic metabolism. Moreover, comprehensive lipidomics analysis elucidated different lipids adaptation between VAT and SAT in adrenergic-induced browning. CL316, 243 induced browning heterogeneity of VAT and SAT with more dramatic alteration of total lipid classes and individual molecular lipid species in VAT rather than SAT, though VAT is resistant to browning. Specifically, CL316, 243 stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. Further study uncovered that the lipids remodeling heterogeneity of VAT and SAT may attribute to a more significant alteration of lipids metabolism genes in VAT rather than SAT in response to CL316,243 treatment. CONCLUSION Our datasets provide acomprehensive analysis of lipids metabolic heterogeneity between VAT and SAT browning and may provide promising lipid targets to motivate WAT browning.

关键词： visceral adipose tissue subcutaneous adipose tissue browning heterogeneity beta-3 adrenergic receptor agonist

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