title: Imaging Mass Spectrometry Reveals Acyl-Chain- and Region-Specific Sphingolipid Metabolism in the Kidneys of Sphingomyelin Synthase 2-Deficient Mice.
abstract: Obesity was reported to cause kidney injury by excessive accumulation of sphingolipids such as sphingomyelin and ceramide. Sphingomyelin synthase 2 (SMS2) is an important enzyme for hepatic sphingolipid homeostasis and its dysfunction is considered to result in fatty liver disease. The expression of SMS2 is also high in the kidneys. However, the contribution of SMS2 on renal sphingolipid metabolism remains unclear. Imaging mass spectrometry is a powerful tool to visualize the distribution and provide quantitative data on lipids in tissue sections. Thus, in this study, we analyzed the effects of SMS2 deficiency on the distribution and concentration of sphingomyelins in the liver and kidneys of mice fed with a normal-diet or a high-fat-diet using imaging mass spectrometry and liquid chromatography/electrospray ionization-tandem mass spectrometry. Our study revealed that high-fat-diet increased C18-C22 sphingomyelins, but decreased C24-sphingomyelins, in the liver and kidneys of wild-type mice. By contrast, SMS2 deficiency decreased C18-C24 sphingomyelins in the liver. Although a similar trend was observed in the whole-kidneys, the effects were minor. Interestingly, imaging mass spectrometry revealed that sphingomyelin localization was specific to each acyl-chain length in the kidneys. Further, SMS2 deficiency mainly decreased C22-sphingomyelin in the renal medulla and C24-sphingomyelins in the renal cortex. Thus, imaging mass spectrometry can provide visual assessment of the contribution of SMS2 on acyl-chain- and region-specific sphingomyelin metabolism in the kidneys.
authors.affiliation: Department of Integrated Molecular Imaging, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.|Shionogi Innovation Center for Drug Discovery, Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Sapporo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Shionogi Innovation Center for Drug Discovery, Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Sapporo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Wakabayashi
authors.affiliation: Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.|Laboratory of Bioanalysis and Molecular Imaging, Faculty of Pharmaceutical Science, Hokkaido University, Sapporo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Shionogi Innovation Center for Drug Discovery, Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Sapporo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshioka
authors.affiliation: Shionogi Innovation Center for Drug Discovery, Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Sapporo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Higashino
authors.affiliation: Shionogi Innovation Center for Drug Discovery, Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Sapporo, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Numata
authors.affiliation: Drug Discovery Technologies, Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Okuda
authors.affiliation: Department of Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Biomembrane and Biofunctional Chemistry, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Biomembrane and Biofunctional Chemistry, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Igarashi
authors.affiliation: Department of Integrated Molecular Imaging, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.|Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
mesh_terms: D000818:Animals; D002518:Ceramides / Q000378:metabolism; D059305:Diet, High-Fat; D006801:Humans; D007668:Kidney / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000293:injuries / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D013107:Sphingolipids / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D002518:Ceramides; D013107:Sphingolipids; D013109:Sphingomyelins; D017855:Transferases (Other Substituted Phosphate Groups); C543123:Sgms2 protein, mouse