Disclosure: The authors declared no conflict of interest.
Reversal of dopamine system dysfunction in response to high-fat diet
Article first published online: 29 MAY 2013
Copyright © 2013 The Obesity Society
Volume 21, Issue 12, pages 2513–2521, December 2013
How to Cite
Carlin, J., Hill-Smith, T. E., Lucki, I. and Reyes, T. M. (2013), Reversal of dopamine system dysfunction in response to high-fat diet. Obesity, 21: 2513–2521. doi: 10.1002/oby.20374
Full financial disclosures and author notes may be found in the online version of this article.
Funding agencies: This research was supported by the grants MH087978, MH86599, and T32 GM008076 from the National Institutes of Health (NIH). This work was supported by the following grants from the National Institutes of Health (NIH): MH087978 (T.M.R.), MH86599 (I.L.), and T32 GM008076 (J.L.C).
- Issue published online: 3 DEC 2013
- Article first published online: 29 MAY 2013
- Accepted manuscript online: 20 MAR 2013 02:07AM EST
- Manuscript Accepted: 31 DEC 2012
- Manuscript Received: 16 NOV 2012
- National Institutes of Health (NIH). Grant Numbers: MH087978, MH86599, T32 GM008076
To test whether high-fat diet (HFD) decreases dopaminergic tone in reward regions of the brain and evaluate whether these changes reverse after removal of the HFD.
Design and Methods
Male and female mice were fed a 60% HFD for 12 weeks. An additional group was evaluated 4 weeks after removal of the HFD. These groups were compared with control fed, age-matched controls. Sucrose and saccharin preference was measured along with mRNA expression of dopamine (DA)-related genes by Real Time-quantitative PCR (RT-qPCR). DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography. DNA methylation of the dopamine transporter (DAT) promoter was measured by methylated DNA immunoprecipitation and RT-qPCR.
After chronic HFD, sucrose preference was reduced, and then normalized after removal of the HFD. Decreased expression of DA genes, decreased DA content and alterations in DAT promoter methylation, was observed. Importantly, response to HFD and the persistence of changes depended on sex and brain region.
These data identify diminished DA tone after early-life chronic HFD with a complex pattern of reversal and persistence that varies by both sex and brain region. Central nervous system changes that did not reverse after HFD withdrawal may contribute to the difficulty in maintaining weight-loss after diet intervention.