BACKGROUND: Abnormal lipid metabolism contributes to the pathogenesis of diabetes, but it is uncertain whether it plays a role in the development of diabetic nephropathy (DN). While rapamycin was shown to prevent DN development in streptozotocin (STZ)-induced diabetic rats in our previous studies, it is unknown if it intervenes with lipid metabolism. METHODS: We divided the rats into four groups: normal control rats, rapamycin-treated normal rats, diabetic rats and rapamycin-treated DN rats. The apoptosis was evaluated by immunohistochemistry. The crude lipid and sphingolipid were extracted from rat renal cortex and analysed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The expression of the three key enzymes in sphingolipid metabolism including serine palmitoyltransferase, acid sphingomyelinase and sphingomyelin synthase was measured by western blot and immunohistochemistry in rat renal cortex. RESULTS: The level of apoptosis was increased in diabetic rats, and rapamycin treatment reduced apoptosis. STZ treatment significantly increased formation of many sphingolipids species through elevated de novo synthesis. These changes were inhibited by treatment with rapamycin. CONCLUSIONS: Accumulation of sphingolipids contributes to STZ-induced diabetes, and the therapeutic effect of rapamycin on diabetic nephropathy is partly through suppression of sphingolipid abnormality.
BACKGROUND: Abnormal lipid metabolism contributes to the pathogenesis of diabetes, but it is uncertain whether it plays a role in the development of diabetic nephropathy (DN). While rapamycin was shown to prevent DN development in streptozotocin (STZ)-induced diabeticrats in our previous studies, it is unknown if it intervenes with lipid metabolism. METHODS: We divided the rats into four groups: normal control rats, rapamycin-treated normal rats, diabeticrats and rapamycin-treated DN rats. The apoptosis was evaluated by immunohistochemistry. The crude lipid and sphingolipid were extracted from rat renal cortex and analysed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The expression of the three key enzymes in sphingolipid metabolism including serine palmitoyltransferase, acid sphingomyelinase and sphingomyelin synthase was measured by western blot and immunohistochemistry in rat renal cortex. RESULTS: The level of apoptosis was increased in diabeticrats, and rapamycin treatment reduced apoptosis. STZ treatment significantly increased formation of many sphingolipids species through elevated de novo synthesis. These changes were inhibited by treatment with rapamycin. CONCLUSIONS: Accumulation of sphingolipids contributes to STZ-induced diabetes, and the therapeutic effect of rapamycin on diabetic nephropathy is partly through suppression of sphingolipid abnormality.
Authors: Kerri J Grove; Paul A Voziyan; Jeffrey M Spraggins; Suwan Wang; Paisit Paueksakon; Raymond C Harris; Billy G Hudson; Richard M Caprioli Journal: J Lipid Res Date: 2014-05-26 Impact factor: 5.922
Authors: D Pastore; D Della-Morte; A Coppola; B Capuani; M F Lombardo; F Pacifici; F Ferrelli; R Arriga; C Mammi; M Federici; A Bellia; N Di Daniele; M Tesauro; G Donadel; D Noto; P Sbraccia; G Sconocchia; D Lauro Journal: Cell Death Dis Date: 2015-09-17 Impact factor: 8.469
Authors: Peter J Meikle; Gerard Wong; Christopher K Barlow; Jacquelyn M Weir; Melissa A Greeve; Gemma L MacIntosh; Laura Almasy; Anthony G Comuzzie; Michael C Mahaney; Adam Kowalczyk; Izhac Haviv; Narelle Grantham; Dianna J Magliano; Jeremy B M Jowett; Paul Zimmet; Joanne E Curran; John Blangero; Jonathan Shaw Journal: PLoS One Date: 2013-09-27 Impact factor: 3.240