|This high-fat fed rat sure looks happy to me (source)|
Vucetic et. al. (2012) tested the levels of dopamine-related gene expression (via mRNA) in the hypothalamus and the ventral tegmental area (VTA). The hypothalamus is important because it controls your levels of hunger as well as many other things. The VTA is important because it is the main source of dopamine to the ventral striatum (AKA the Nucleus Accumbens). The VTA-nucleus accumbens pathway is generally thought to signify 'reward' when it is activated. Sex, Drugs, Music, and lots of other 'pleasurable' activities all activate this pathway. So alterations in the dopamine levels here might change how 'rewarded' a person (or mouse in this case) feels in response to pleasurable stimuli.
So Vucetic et al., (2012) found that in the VTA, the levels of tyrosine hydroxylase ("TH", an enzyme indicative of how much dopamine can be made) and dopamine active transporter ("DAT", which gets rid of excess dopamine at the synapse) are both reduced in the mice eating the high fat diet.
|Vucetic et al. (2012) Figure 1|
So what does this mean? The authors point out that increased dopamine in the hypothalamus actually promotes eating. Consistent with this idea, the authors show that mice eating the high fat diet actually ate more frequently and ate more total food. Secondly, when there is less dopamine in the VTA, it is likely that a rewarding stimuli will seem less rewarding.
In the author's words:
"Collectively, these behaviors have the potential to promote obesity in two distinct ways: (i) through an increase in food intake and (ii) by increasing the drive for palatable food, as the animal with a blunted response to palatable foods may seek and/or consume these food relatively more than a normal animal in order to reach the same rewarding response. "So basically the mice aren't obese because the food they are eating is high fat, they are obese because they are eating MORE food. But of course, they are eating more food because the high fat diet makes them 'want' to eat more food, so the high fat diet is indirectly causing the weight gain.
It is truly a vicious cycle.
*Note: They also look at epigenetic effects on the TH and DAT promoter DNA. If you are interested in that aspect of the study, comment and I can do a follow-up post explaining it, or you can just read the study for yourself, following the link below.
Vucetic Z, Carlin JL, Totoki K, & Reyes TM (2012). Epigenetic dysregulation of the dopamine system in diet-induced obesity. Journal of neurochemistry, 120 (6), 891-8 PMID: 22220805