Differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes
Considering the major role of insulin signaling on fatty acid synthesis via stimulation of lipogenic enzymes, differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis have been investigated by comparing the individual lipogenic fluxes in WT and IRS-1 knockout (I...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
2004
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| Online Access: | http://hdl.handle.net/1721.1/7478 |
| _version_ | 1811090299225636864 |
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| author | Yoo, Hyuntae Antoniewicz, Maciek Kelleher, Joanne K. Stephanopoulos, Gregory |
| author_facet | Yoo, Hyuntae Antoniewicz, Maciek Kelleher, Joanne K. Stephanopoulos, Gregory |
| author_sort | Yoo, Hyuntae |
| collection | MIT |
| description | Considering the major role of insulin signaling on fatty acid synthesis via stimulation of lipogenic enzymes, differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis have been investigated by comparing the individual lipogenic fluxes in WT and IRS-1 knockout (IRS-1 KO) brown adipocytes. Results from experiments on WT and IRS-1 KO cells incubated with [5-¹³C] glutamine were consistent with the existence of reductive carboxylation pathway. Analysis of isotopomer distribution of nine metabolites related to the lipogenic routes from glucose and glutamine in IRS-1 KO cells using [U-¹³C] glutamine as compared to that in WT cells indicated that flux through reductive carboxylation pathway was diminished while flux through conventional TCA cycle was stimulated due to absence of insulin signaling in IRS-1 KO cells. This observation was confirmed by quantitative estimation of individual lipogenic fluxes in IRS-1 KO cells and their comparison with fluxes in WT cells. Thus, these results suggest that glutamine’s substantial contribution to fatty acid synthesis can be directly manipulated by controlling the flux through reductive carboxylation of alpha-ketoglutarate to citrate using hormone (insulin). |
| first_indexed | 2024-09-23T14:41:41Z |
| format | Article |
| id | mit-1721.1/7478 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:41:41Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | mit-1721.1/74782019-04-10T21:48:41Z Differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes Yoo, Hyuntae Antoniewicz, Maciek Kelleher, Joanne K. Stephanopoulos, Gregory brown adipocyte fatty acid synthesis insulin signaling reductive carboxylation pathway 5-13C U-13C Considering the major role of insulin signaling on fatty acid synthesis via stimulation of lipogenic enzymes, differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis have been investigated by comparing the individual lipogenic fluxes in WT and IRS-1 knockout (IRS-1 KO) brown adipocytes. Results from experiments on WT and IRS-1 KO cells incubated with [5-¹³C] glutamine were consistent with the existence of reductive carboxylation pathway. Analysis of isotopomer distribution of nine metabolites related to the lipogenic routes from glucose and glutamine in IRS-1 KO cells using [U-¹³C] glutamine as compared to that in WT cells indicated that flux through reductive carboxylation pathway was diminished while flux through conventional TCA cycle was stimulated due to absence of insulin signaling in IRS-1 KO cells. This observation was confirmed by quantitative estimation of individual lipogenic fluxes in IRS-1 KO cells and their comparison with fluxes in WT cells. Thus, these results suggest that glutamine’s substantial contribution to fatty acid synthesis can be directly manipulated by controlling the flux through reductive carboxylation of alpha-ketoglutarate to citrate using hormone (insulin). Singapore-MIT Alliance (SMA) 2004-12-15T19:28:10Z 2004-12-15T19:28:10Z 2005-01 Article http://hdl.handle.net/1721.1/7478 en Molecular Engineering of Biological and Chemical Systems (MEBCS); 415564 bytes application/pdf application/pdf |
| spellingShingle | brown adipocyte fatty acid synthesis insulin signaling reductive carboxylation pathway 5-13C U-13C Yoo, Hyuntae Antoniewicz, Maciek Kelleher, Joanne K. Stephanopoulos, Gregory Differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes |
| title | Differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes |
| title_full | Differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes |
| title_fullStr | Differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes |
| title_full_unstemmed | Differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes |
| title_short | Differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes |
| title_sort | differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis in brown adipocytes |
| topic | brown adipocyte fatty acid synthesis insulin signaling reductive carboxylation pathway 5-13C U-13C |
| url | http://hdl.handle.net/1721.1/7478 |
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