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I, and a number of other CR practitioners I know, eat what most people would consider a very monotonous diet - eating (virtually) the same thing nearly every day. And usually not what most people would consider the tastiest of foods either, since most people's palates find the tastiest foods to be those that are generally not very health (e.g. cakes, pies, cookies, pizza, chips, etc.), and thus we tend to limit them or avoid them altogether.

 

As a result, my wife and family have often wondered how I can stand to eat the same thing every day, and I've wondered it too. Why do I look forward to eating, and specifically the taste of, my same-old (one) meal every day?

 

This new study [1] (press release) posted by Al Pater to the CR email list (thanks Al!) may provide a clue. Some caution is on order in extrapolating to humans the results of [1], since it was conducted in isolated slices of neurons from the brains of rats. But it is interesting nonetheless for what it suggests about the reward value of food, particularly for animals (and maybe people) subjected to calorie restriction. So here goes...

 

In the main part of the study, they had three groups of rats, labelled FR (food restricted), AL (ad lib) and OB (obese rats, fed three different diets:

 

AL rats had free access to standard rat chow. [FR] rats received 40–50% of AL intake of standard rat chow daily until body weight was reduced by 20%, after which food was titrated to maintain this weight. OB rats had free access to rat chow and chocolate Ensure, a highly palatable liquid with moderately high fat and sugar

 

Not surprisingly, by the end of the four week diet intervention, the OB rats were fat, and the FR rats were thin and had a much lower level of circulating serum insulin than either AL or OB rats.

 

They then isolated slices from parts of the striatum of the brains of the rats in the three groups. The striatum is known to be part of the mammalian reward system, and is the primary brain area associated with the neurotransmitter dopamine, the release of which is known to be associated with all types of reward, including food reward, not to mention the reward from drugs like cocaine.

 

Slices from the FR rats were exposed to insulin, since insulin level in the brain have been previously shown to influence dopamine release. But the previous results were ambiguous - insulin has previously appeared to increase both dopamine release and dopamine reuptake, so it hasn't been clear whether increased insulin in the brain (e.g. after eating a meal with glucose) would result in a net increase or decrease in dopamine signalling, particularly in the reward center (striatum).

 

What these researchers found was quite unambiguous. In slices from the FR rats' striatum, dopamine release was extremely sensitive to insulin level - in fact 10x more sensitive than the AL rats. In other words, it took very little insulin for the FR rats' striatum to release lots of dopamine. In contrast, the obese (OB) rats showed just the opposite. Their tendency to release dopamine was a lot less sensitive to insulin than AL, and especially FR rats brain slices. Here is the relevant graph from the full text of the paper:

 

E4kRRkM.png

 

It shows the amount of dopamine released (y-axis) in response to various levels of infused insulin (x-axis) in three different parts of the striatum, for the FR (blue) and OB (maroon) rats. What you can see is that in all three areas, it took nearly two orders of magnitude more insulin to trigger the same amount of dopamine release in the OB rats as the FR rats (e.g. 10-30 nM for OB vs 0.3 nM for FR). Put another way - at low levels of insulin (e.g. 0.3 or 1.0 nM), the FR rats brains were releasing a substantial amount of dopamine, significantly more than AL controls, while the OB rats weren't releasing any dopamine (i.e. 0% of AL controls).

 

In short, CR rats (and maybe humans) appear to get a lot more "bang for their buck" from food - i.e. a greater feeling of reward (via increased dopamine) from a given amount of food/glucose/insulin ingested. So perhaps this could explain in part why CR practitioners find their modest diets (modest both in terms of calories and palatability) to continue to be rewarding - we're getting a big dopamine release relatively to 'normal' people because of the increased sensitivity of our brain's reward center to insulin.

 

Regarding palatability, the researchers in [1] went a step further, using a different set of rats (obviously, since the first set was dead  :(xyz).

 

In this second part of the experiment, they investigated the effect of blocking insulin action in the reward center of behaving rats on the development of food preferences. Specifically, they gave rats two glucose sweetened beverages, with different flavorings added to make them distinguishable, but both still quite palatable. They gave rats each of the two drinks, but alternating them from one day to the next. Whenever the rats received one of them, they paired it with an injection of an insulin-blocking agent to their striatum, to prevent the insulin spike following consumption of the drink from triggering a rewarding dopamine release. With the other beverage, they didn't block insulin, and therefore didn't block the rewarding release of dopamine that resulted from consuming the second beverage.

 

As you might predict by now, when the rats were given free access to the two beverages after this conditioning, the rats preferred the beverage where insulin hadn't been blocked, presumably because they'd developed a taste preference for that flavor as a result of its consistent pairing with dopamine release in the striatum.

 

Extrapolating to human CR practitioners - this might explain why we find our simple, monotonous diet so palatable. Specifically, our brains release a lot of dopamine in response to the insulin spike when we eat, so the taste of our monotonous diet becomes associated with the "good feeling" produced by dopamine, in a way not so different from the positive sensation produced by cocaine, which blocks dopamine reuptake at synapses in the striatum, thereby effectively increasing dopamine signalling.

 

In summary, this study appears to suggest (assuming these rat results can be extrapolated to humans) that one's palate (i.e. food preferences) really does change, as many people have reported, as a result of eating a calorie-restricted, healthy, but not-especially-tasty diet for an extended period of time, and that this change is mediated by insulin signaling, insulin sensitivity, and dopamine release in the brain's reward center.

 

--Dean

 

------------

[1] Nat Commun. 2015 Oct 27;6:8543. doi: 10.1038/ncomms9543.

Insulin enhances striatal dopamine release by activating cholinergic interneurons
and thereby signals reward.

Stouffer MA(1,)(2), Woods CA(3), Patel JC(2), Lee CR(2), Witkovsky P(4), Bao
L(1,)(2), Machold RP(5), Jones KT(6), de Vaca SC(6), Reith ME(6,)(7), Carr
KD(6,)(7), Rice ME(1,)(2).

Free full text: http://www.nature.com/ncomms/2015/151027/ncomms9543/full/ncomms9543.html

Press release: http://www.eurekalert.org/pub_releases/2015-10/nlmc-nrf102215.php

Insulin activates insulin receptors (InsRs) in the hypothalamus to signal satiety
after a meal. However, the rising incidence of obesity, which results in
chronically elevated insulin levels, implies that insulin may also act in brain
centres that regulate motivation and reward. We report here that insulin can
amplify action potential-dependent dopamine (DA) release in the nucleus accumbens
(NAc) and caudate-putamen through an indirect mechanism that involves striatal
cholinergic interneurons that express InsRs. Furthermore, two different chronic
diet manipulations in rats, food restriction (FR) and an obesogenic (OB) diet,
oppositely alter the sensitivity of striatal DA release to insulin, with enhanced
responsiveness in FR, but loss of responsiveness in OB. Behavioural studies show
that intact insulin levels in the NAc shell are necessary for acquisition of
preference for the flavour of a paired glucose solution. Together, these data
imply that striatal insulin signalling enhances DA release to influence food
choices.

PMCID: PMC4624275
PMID: 26503322

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All,

 

Here is a very informative article from Scientific American on recent research into the different pathways involved in "metabolic" vs. "hedonic" hunger - with the latter involving the brain's dopamine reward circuitry, as discussed above. Here are a couple of the most interesting paragraphs:

 

It turns out that extremely sweet or fatty foods captivate the brain’s reward circuit in much the same way that cocaine and gambling do. For much of our evolutionary past, such calorie-dense foods were rare treats that would have provided much needed sustenance, especially in dire times. Back then, gorging on sweets and fats whenever they were available was a matter of survival. In contemporary society—replete with inexpensive, high-calorie grub—this instinct works against us...
 
Research has shown that the brain begins responding to fatty and sugary foods even before they enter our mouth. Merely seeing a desirable item excites the reward circuit. As soon as such a dish touches the tongue, taste buds send signals to various regions of the brain, which in turn responds by spewing the neurochemical dopamine. The result is an intense feeling of pleasure. Frequently overeating highly palatable foods saturates the brain with so much dopamine that it eventually adapts by desensitizing itself, reducing the number of cellular receptors that recognize and respond to the neurochemical. Consequently, the brains of overeaters demand a lot more sugar and fat to reach the same threshold of pleasure as they once experienced with smaller amounts of the foods. These people may, in fact, continue to overeat as a way of recapturing or even maintaining a sense of well-being.

 

--Dean

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"Research has shown that the brain begins responding to fatty and sugary foods even before they enter our mouth."

 

That's me, but it is not just fat and sugar to which my brain responds!  If I have eaten less than 3100 to 3400 calories on any given day, the sight, smell or even simply reading about almost any kind of food (haggis might be an exception) excites an anticipation of future reward.  I have referred to this here previously using the expression ''food prompt" or "hunger prompt".  It turns off somewhere between 3100 and 3400 calories, after which, I have determined by experiment, I no longer feel a need to open the fridge door to find something more to eat, no matter the provocation.

 

I have to avoid these prompts at all costs, in the absence of which I generally do not feel hungry.  But if someone with a BMI of 35 puts a hot pizza in front of me I would have no trouble eating the whole thing.  (I won't bore you with a repeat of my nine hamburgers story.)

 

Rodney.

 

==========

 

"The unverified conventional wisdom is almost invariably mistaken."

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