Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression.
The development of diet-induced obesity (DIO) can potently alter multiple aspects of dopamine signaling, including dopamine transporter (DAT) expression and dopamine reuptake. However, the time-course of diet-induced changes in DAT expression and function and whether such changes are dependent upon...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516454/?tool=EBI |
| _version_ | 1818723871026577408 |
|---|---|
| author | Jackson J Cone Elena H Chartoff David N Potter Stephanie R Ebner Mitchell F Roitman |
| author_facet | Jackson J Cone Elena H Chartoff David N Potter Stephanie R Ebner Mitchell F Roitman |
| author_sort | Jackson J Cone |
| collection | DOAJ |
| description | The development of diet-induced obesity (DIO) can potently alter multiple aspects of dopamine signaling, including dopamine transporter (DAT) expression and dopamine reuptake. However, the time-course of diet-induced changes in DAT expression and function and whether such changes are dependent upon the development of DIO remains unresolved. Here, we fed rats a high (HFD) or low (LFD) fat diet for 2 or 6 weeks. Following diet exposure, rats were anesthetized with urethane and striatal DAT function was assessed by electrically stimulating the dopamine cell bodies in the ventral tegmental area (VTA) and recording resultant changes in dopamine concentration in the ventral striatum using fast-scan cyclic voltammetry. We also quantified the effect of HFD on membrane associated DAT in striatal cell fractions from a separate group of rats following exposure to the same diet protocol. Notably, none of our treatment groups differed in body weight. We found a deficit in the rate of dopamine reuptake in HFD rats relative to LFD rats after 6 but not 2 weeks of diet exposure. Additionally, the increase in evoked dopamine following a pharmacological challenge of cocaine was significantly attenuated in HFD relative to LFD rats. Western blot analysis revealed that there was no effect of diet on total DAT protein. However, 6 weeks of HFD exposure significantly reduced the 50 kDa DAT isoform in a synaptosomal membrane-associated fraction, but not in a fraction associated with recycling endosomes. Our data provide further evidence for diet-induced alterations in dopamine reuptake independent of changes in DAT production and demonstrates that such changes can manifest without the development of DIO. |
| first_indexed | 2024-12-17T21:17:24Z |
| format | Article |
| id | doaj.art-677daa4cc5a949db8f554a72160863ee |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T21:17:24Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-677daa4cc5a949db8f554a72160863ee2022-12-21T21:32:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5825110.1371/journal.pone.0058251Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression.Jackson J ConeElena H ChartoffDavid N PotterStephanie R EbnerMitchell F RoitmanThe development of diet-induced obesity (DIO) can potently alter multiple aspects of dopamine signaling, including dopamine transporter (DAT) expression and dopamine reuptake. However, the time-course of diet-induced changes in DAT expression and function and whether such changes are dependent upon the development of DIO remains unresolved. Here, we fed rats a high (HFD) or low (LFD) fat diet for 2 or 6 weeks. Following diet exposure, rats were anesthetized with urethane and striatal DAT function was assessed by electrically stimulating the dopamine cell bodies in the ventral tegmental area (VTA) and recording resultant changes in dopamine concentration in the ventral striatum using fast-scan cyclic voltammetry. We also quantified the effect of HFD on membrane associated DAT in striatal cell fractions from a separate group of rats following exposure to the same diet protocol. Notably, none of our treatment groups differed in body weight. We found a deficit in the rate of dopamine reuptake in HFD rats relative to LFD rats after 6 but not 2 weeks of diet exposure. Additionally, the increase in evoked dopamine following a pharmacological challenge of cocaine was significantly attenuated in HFD relative to LFD rats. Western blot analysis revealed that there was no effect of diet on total DAT protein. However, 6 weeks of HFD exposure significantly reduced the 50 kDa DAT isoform in a synaptosomal membrane-associated fraction, but not in a fraction associated with recycling endosomes. Our data provide further evidence for diet-induced alterations in dopamine reuptake independent of changes in DAT production and demonstrates that such changes can manifest without the development of DIO.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516454/?tool=EBI |
| spellingShingle | Jackson J Cone Elena H Chartoff David N Potter Stephanie R Ebner Mitchell F Roitman Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression. PLoS ONE |
| title | Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression. |
| title_full | Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression. |
| title_fullStr | Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression. |
| title_full_unstemmed | Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression. |
| title_short | Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression. |
| title_sort | prolonged high fat diet reduces dopamine reuptake without altering dat gene expression |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516454/?tool=EBI |
| work_keys_str_mv | AT jacksonjcone prolongedhighfatdietreducesdopaminereuptakewithoutalteringdatgeneexpression AT elenahchartoff prolongedhighfatdietreducesdopaminereuptakewithoutalteringdatgeneexpression AT davidnpotter prolongedhighfatdietreducesdopaminereuptakewithoutalteringdatgeneexpression AT stephanierebner prolongedhighfatdietreducesdopaminereuptakewithoutalteringdatgeneexpression AT mitchellfroitman prolongedhighfatdietreducesdopaminereuptakewithoutalteringdatgeneexpression |