Sphingolipid Biology and Regulation of Metabolism

鞘脂生物学和代谢调节

• 批准号: 10697781
• 负责人: Richard Proia
• 金额: $ 101.19万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697781
• 关键词: Biology; Cellular Metabolic Process; Diabetes Mellitus; Fatty Acids; Goals; Immune; Link; Lipids; Metabolic Pathway; Metabolism; Mus; Obesity; Palmitoyl Coenzyme A; Pathway interactions; Phospholipids; Process; Regulation; Role; Signal Pathway; Sphingolipids; Sterols; dietary; enzyme activity

The sphingolipid metabolic pathway is initiated by the incorporation of palmitoyl CoA, derivative of fatty acids, and ultimately provides substrates for the synthesis of other lipids. Thus the sphingolipid metabolic pathway is highly integrated with other dietary and structural lipid metabolic pathways. Furthermore, the sphingolipid metabolites themselves are bioactive and alter cell metabolism via signaling pathways. We have developed, and continue to develop genetically altered mice with modified expression of key sphingolipid enzyme activities in order to study the role of the pathway in metabolism including their role in diabetes and obesity.

鞘脂代谢途径由脂肪酸衍生物棕榈酰辅酶A的掺入启动，并最终为其他脂质的合成提供底物。 因此，鞘脂代谢途径与其他饮食和结构脂质代谢途径高度整合。此外，鞘脂代谢物本身具有生物活性，并通过信号通路改变细胞代谢。我们已经并将继续开发关键鞘脂酶活性表达发生改变的基因改造小鼠，以研究该途径在代谢中的作用，包括其在糖尿病和肥胖中的作用。

项目成果

Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking.

• DOI: 10.1093/eurheartj/ehab412
• 发表时间: 2021-11-14
• 期刊: European heart journal
• 影响因子: 39.3
• 作者: Andersson L;Cinato M;Mardani I;Miljanovic A;Arif M;Koh A;Lindbom M;Laudette M;Bollano E;Omerovic E;Klevstig M;Henricsson M;Fogelstrand P;Swärd K;Ekstrand M;Levin M;Wikström J;Doran S;Hyötyläinen T;Sinisalu L;Orešič M;Tivesten Å;Adiels M;Bergo MO;Proia R;Mardinoglu A;Jeppsson A;Borén J;Levin MC
• 通讯作者: Levin MC

S1P1 receptor directs the release of immature B cells from bone marrow into blood.

• DOI: 10.1084/jem.20092210
• 发表时间: 2010-05-10
• 期刊: The Journal of experimental medicine
• 作者: Allende ML;Tuymetova G;Lee BG;Bonifacino E;Wu YP;Proia RL
• 通讯作者: Proia RL

Sphingosine kinase-2 prevents macrophage cholesterol accumulation and atherosclerosis by stimulating autophagic lipid degradation

• DOI: 10.1038/s41598-019-54877-6
• 发表时间: 2019-12-04
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Ishimaru, Kazuhiro;Yoshioka, Kazuaki;Takuwa, Yoh
• 通讯作者: Takuwa, Yoh

Ablation of PPARγ in subcutaneous fat exacerbates age-associated obesity and metabolic decline.

皮下脂肪中 PPAR γ 的消除会加剧与年龄相关的肥胖和代谢下降

• DOI: 10.1111/acel.12721
• 发表时间: 2018-04
• 期刊: Aging cell
• 影响因子: 7.8
• 作者: Xu L;Ma X;Verma NK;Wang D;Gavrilova O;Proia RL;Finkel T;Mueller E
• 通讯作者: Mueller E

Shaping the landscape: metabolic regulation of S1P gradients.

• DOI: 10.1016/j.bbalip.2012.06.007
• 发表时间: 2013-01
• 期刊: Biochimica et biophysica acta
• 作者: Olivera A;Allende ML;Proia RL
• 通讯作者: Proia RL