Michael SM Mah, Enyuan Cao, Dovile Anderson, Alistair Escott, Surafel Tegegne, Gracia Gracia, Joel Schmitz, Susanne Brodesser, Colby Zaph, Darren J. Creek, Jiwon Hong, John A. Windsor, Anthony RJ Phillips, Natalie L. Trevaskis, Mark A. Febbraio, Sarah M. Turpin-Nolan
{"title":"高脂肪摄入会促使肠道产生C16:0神经酰胺并在乳糜微粒中组装。","authors":"Michael SM Mah, Enyuan Cao, Dovile Anderson, Alistair Escott, Surafel Tegegne, Gracia Gracia, Joel Schmitz, Susanne Brodesser, Colby Zaph, Darren J. Creek, Jiwon Hong, John A. Windsor, Anthony RJ Phillips, Natalie L. Trevaskis, Mark A. Febbraio, Sarah M. Turpin-Nolan","doi":"10.1126/sciadv.adp2254","DOIUrl":null,"url":null,"abstract":"<div >Consumption of a diet rich in saturated fat increases lipid absorption from the intestine, assembly into chylomicrons, and delivery to metabolic tissues via the lymphatic and circulatory systems. Accumulation of ceramide lipids, composed of sphingosine and a fatty acid, in metabolic tissues contributes to the pathogenesis of cardiovascular diseases, type 2 diabetes mellitus and cancer. Using a mesenteric lymph duct cannulated rat model, we showed that ceramides are generated by the intestine and assembled into chylomicrons, which are transported via the mesenteric lymphatic system. A lipidomic screen of intestinal-derived chylomicrons identified a diverse range of fatty acid, sphingolipid, and glycerolipid species that have not been previously detected in chylomicrons, including the metabolically deleterious C<sub>16:0</sub> ceramide that increased in response to high-fat feeding in rats and human high-lipid meal replacement enteral feeding. In conclusion, high-fat feeding increases the export of intestinal-derived C<sub>16:0</sub> ceramide in chylomicrons, identifying a potentially unknown mechanism through which ceramides are transported systemically to contribute to metabolic dysfunction.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7000,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp2254","citationCount":"0","resultStr":"{\"title\":\"High-fat feeding drives the intestinal production and assembly of C16:0 ceramides in chylomicrons\",\"authors\":\"Michael SM Mah, Enyuan Cao, Dovile Anderson, Alistair Escott, Surafel Tegegne, Gracia Gracia, Joel Schmitz, Susanne Brodesser, Colby Zaph, Darren J. Creek, Jiwon Hong, John A. Windsor, Anthony RJ Phillips, Natalie L. Trevaskis, Mark A. Febbraio, Sarah M. Turpin-Nolan\",\"doi\":\"10.1126/sciadv.adp2254\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div >Consumption of a diet rich in saturated fat increases lipid absorption from the intestine, assembly into chylomicrons, and delivery to metabolic tissues via the lymphatic and circulatory systems. Accumulation of ceramide lipids, composed of sphingosine and a fatty acid, in metabolic tissues contributes to the pathogenesis of cardiovascular diseases, type 2 diabetes mellitus and cancer. Using a mesenteric lymph duct cannulated rat model, we showed that ceramides are generated by the intestine and assembled into chylomicrons, which are transported via the mesenteric lymphatic system. A lipidomic screen of intestinal-derived chylomicrons identified a diverse range of fatty acid, sphingolipid, and glycerolipid species that have not been previously detected in chylomicrons, including the metabolically deleterious C<sub>16:0</sub> ceramide that increased in response to high-fat feeding in rats and human high-lipid meal replacement enteral feeding. In conclusion, high-fat feeding increases the export of intestinal-derived C<sub>16:0</sub> ceramide in chylomicrons, identifying a potentially unknown mechanism through which ceramides are transported systemically to contribute to metabolic dysfunction.</div>\",\"PeriodicalId\":21609,\"journal\":{\"name\":\"Science Advances\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.7000,\"publicationDate\":\"2024-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.science.org/doi/reader/10.1126/sciadv.adp2254\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Advances\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://www.science.org/doi/10.1126/sciadv.adp2254\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Advances","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/sciadv.adp2254","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
High-fat feeding drives the intestinal production and assembly of C16:0 ceramides in chylomicrons
Consumption of a diet rich in saturated fat increases lipid absorption from the intestine, assembly into chylomicrons, and delivery to metabolic tissues via the lymphatic and circulatory systems. Accumulation of ceramide lipids, composed of sphingosine and a fatty acid, in metabolic tissues contributes to the pathogenesis of cardiovascular diseases, type 2 diabetes mellitus and cancer. Using a mesenteric lymph duct cannulated rat model, we showed that ceramides are generated by the intestine and assembled into chylomicrons, which are transported via the mesenteric lymphatic system. A lipidomic screen of intestinal-derived chylomicrons identified a diverse range of fatty acid, sphingolipid, and glycerolipid species that have not been previously detected in chylomicrons, including the metabolically deleterious C16:0 ceramide that increased in response to high-fat feeding in rats and human high-lipid meal replacement enteral feeding. In conclusion, high-fat feeding increases the export of intestinal-derived C16:0 ceramide in chylomicrons, identifying a potentially unknown mechanism through which ceramides are transported systemically to contribute to metabolic dysfunction.
期刊介绍:
Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.