The FoxOs are in the ApoM house
The prevalence of metabolic syndrome continues to increase globally and heightens the risk for cardiovascular disease (CVD). Insulin resistance is a core pathophysiologic mechanism that causes abnormal carbohydrate metabolism and atherogenic changes in circulating lipoprotein quantity and function....
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2022-04-01
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| Series: | The Journal of Clinical Investigation |
| Online Access: | https://doi.org/10.1172/JCI158471 |
| _version_ | 1828781144353538048 |
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| author | MacRae F. Linton Patricia G. Yancey Zoe M. Leuthner Jonathan D. Brown |
| author_facet | MacRae F. Linton Patricia G. Yancey Zoe M. Leuthner Jonathan D. Brown |
| author_sort | MacRae F. Linton |
| collection | DOAJ |
| description | The prevalence of metabolic syndrome continues to increase globally and heightens the risk for cardiovascular disease (CVD). Insulin resistance is a core pathophysiologic mechanism that causes abnormal carbohydrate metabolism and atherogenic changes in circulating lipoprotein quantity and function. In particular, dysfunctional HDL is postulated to contribute to CVD risk in part via loss of HDL-associated sphingosine-1-phosphate (S1P). In this issue of the JCI, Izquierdo et al. demonstrate that HDL from humans with insulin resistance contained lower levels of S1P. Apolipoprotein M (ApoM), a protein constituent of HDL that binds S1P and controls bioavailability was decreased in insulin-resistant db/db mice. Gain- and loss-of-function mouse models implicated the forkhead box O transcription factors (FoxO1,3,4) in the regulation of both ApoM and HDL-associated S1P. These data have important implications for potential FoxO-based therapies designed to treat lipid and carbohydrate abnormalities associated with human metabolic disease and CVD. |
| first_indexed | 2024-12-11T17:28:59Z |
| format | Article |
| id | doaj.art-3983c19cadc64343a5e36f629c58f4d7 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-12-11T17:28:59Z |
| publishDate | 2022-04-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-3983c19cadc64343a5e36f629c58f4d72022-12-22T00:56:53ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-04-011327The FoxOs are in the ApoM houseMacRae F. LintonPatricia G. YanceyZoe M. LeuthnerJonathan D. BrownThe prevalence of metabolic syndrome continues to increase globally and heightens the risk for cardiovascular disease (CVD). Insulin resistance is a core pathophysiologic mechanism that causes abnormal carbohydrate metabolism and atherogenic changes in circulating lipoprotein quantity and function. In particular, dysfunctional HDL is postulated to contribute to CVD risk in part via loss of HDL-associated sphingosine-1-phosphate (S1P). In this issue of the JCI, Izquierdo et al. demonstrate that HDL from humans with insulin resistance contained lower levels of S1P. Apolipoprotein M (ApoM), a protein constituent of HDL that binds S1P and controls bioavailability was decreased in insulin-resistant db/db mice. Gain- and loss-of-function mouse models implicated the forkhead box O transcription factors (FoxO1,3,4) in the regulation of both ApoM and HDL-associated S1P. These data have important implications for potential FoxO-based therapies designed to treat lipid and carbohydrate abnormalities associated with human metabolic disease and CVD.https://doi.org/10.1172/JCI158471 |
| spellingShingle | MacRae F. Linton Patricia G. Yancey Zoe M. Leuthner Jonathan D. Brown The FoxOs are in the ApoM house The Journal of Clinical Investigation |
| title | The FoxOs are in the ApoM house |
| title_full | The FoxOs are in the ApoM house |
| title_fullStr | The FoxOs are in the ApoM house |
| title_full_unstemmed | The FoxOs are in the ApoM house |
| title_short | The FoxOs are in the ApoM house |
| title_sort | foxos are in the apom house |
| url | https://doi.org/10.1172/JCI158471 |
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