Hedonic Hunger: Ghrelin and the brain chemistry behind the epidemic of obesity

These days, fast food is among the most accessible items to order, ready to be served at the touch of a button. It is hard not to get excited about a delicious meal high in fat, sugar and calories, arriving in a matter of minutes. Our insatiable desire for high fat foods has grown along with the portion sizes of meals over the past 50 years. In fact, since the 1970s, the average size of food portions from fast-food chains, restaurants and grocery stores has increased by 138% [1]. Caloric intake has risen significantly from the 1960’s worldwide, and continues to rise on a yearly basis as seen in figure 1. It’s safe to say, eating for pleasure rather than survival has become a trend in today’s age. This pattern has been picked up by researchers, who are now studying how high caloric foods change your brain chemistry, causing you to eat more food than is necessary or recommended [2].

This term is coined hedonic hunger, and it is defined as “the drive to eat in order to obtain pleasure in the absence of an energy deficit” [3]. Hedonic hunger has been pegged as one of the main contributors to the surge in obesity rates in developed countries worldwide [4]. Today, I want to shed some light on one single neuropeptide that may be related to hedonic hunger — ghrelin. This particular neuropeptide has been heavily researched, but is not discussed as often in the public eye. I will be explaining what ghrelin is, how it affects your appetite, brain chemistry, and how food companies use it to keep you coming back for more.

Figure 1. Daily supply of calories between 1961 and 2013. Measured by kilo calories.
Taken from: https://ourworldindata.org/food-supply

Ghrelin is classified as an orexigenic peptide. Essentially, it is a hormone that stimulates appetite or food intake. It operates out of the gastrointestinal tract and when it’s released, it makes you want to eat. However, when you’ve eaten and are full, your stomach stretches out, and stretching of the stomach inhibits the release of ghrelin. This is known as a mechano-sensitive process and can be seen in figure 2 [5]. Ghrelin works in complete opposition to another hormone known as leptin. Leptin is released from adipose tissues (fat deposits) when you are full, signalling something called satiety (the sensation of feeling satisfied from food). These two hormones work together to attenuate or stimulate your appetite. If you stop the release of leptin, this will lead to more constant hunger. If you stop the release of ghrelin, you will not crave food as much [6]. Figure 3 summarizes all of this nicely.

Figure 2. The mechano-sensitive process of ghrelin. As the stomach stretches, it signals the stopping of ghrelin release.
Taken from: http://flipper.diff.org/app/pathways/Ghrelin

Quick facts about Ghrelin:

Ghrelin and sleep:

  • Ghrelin release follows a circadian rhythm:
    • Ghrelin increases before expected meal times
    • Slow, steady increase from midnight to dawn
  • Ghrelin expression is negatively correlated with sleep time:
    • Less sleep = more ghrelin
    • More sleep = less ghrelin
    • Sleep disruption can impede ghrelin rhythms, leading to increased ghrelin levels
      • Sensitive to light levels during sleep phase [7, 8]

Ghrelin and weight:

  • Ghrelin release is inversely proportional to body weight
    • Weight loss = increased ghrelin release
    • Weight gain = decreased ghrelin release
    • From an evolutionary perspective, this is done to make sure your weight does not fluctuate too much
  • Ghrelin release increased with stress – leads to stress eating, which leads to weight gain
Figure 3. Leptin and grelin balance before and after eating.
Image Credit: Designua / Shutterstock

Ok, now that we know more about ghrelin, it is time to talk about how it affects your brain chemistry. Although ghrelin is widely expressed in the peripheral nervous system (outside the brain), there is a particular part of the brain where ghrelin receptors have been found — the reward center. The reward center (also known as the meso-limbic pathway) is modulated by the release of a popular neurotransmitter known as dopamine (DA). The release of this neurotransmitter facilitates positive reinforcement of reward-related activities [9]. Ghrelin receptors have been discovered on the cell bodies of dopaminergic neurons in this area. Thus, whenever ghrelin is released, it actually increases the frequency of DA activity in the meso-limbic pathway, reinforcing the behavior of eating food. Of course this has implications for drug or food addictions, where ghrelin has been shown to modulate addictive behavior through this network. This really shouldn’t come as a shock, but here is where food companies capitalize on this network.

Remember when I said eating food decreases the levels of ghrelin in your body? Well, food companies have figured out how to INCREASE ghrelin levels AFTER eating. Their secret? Very high caloric meals. Here is what happens when you eat food high in calories. Meals that come from fast food restaurants usually contain medium-chain fatty acids (MCFAs). These MCFAs are attached with a precursor for grhelin (des-acyl ghrelin) by an enzyme known as Ghrelin O-Acyl Transferase (GOAT) [10,11]. When GOAT catalyzes these two components, the resulting factor is ghrelin! [10,11,12]. This process is known as posttranslational modification of ghrelin [11,12]. Take a look at figure 4 for reference. If you’ve ever felt hungry right after eating McDonald’s or A&W, this may be a reason why (it happened to me last week, and now I’m writing this article). As a result, increased levels of ghrelin leads to positive reinforcement in the reward center of the brain by influencing dopaminergic neurons. Soon, you may develop motivational behaviors towards these types of food. Again, this is an oversimplified illustration, and there are many other processes at work here. But the point is, over time, food companies have figured out how to carefully engineer food to make it more addictive and tasteful.

Figure 4. Posttranslational modification of ghrelin. The precursors Des-acyl ghrelin and medium-chain fatty acids are catalyzed by GOAT to make ghrelin.
Taken from: Physiological roles of ghrelin on obesity. doi: 10.1016/j.orcp.2013.10.002

In concluding, there is ample evidence pointing towards hedonic eating behavior and the orexigenic peptide ghrelin. Clearly, there is a significant correlation between the rise in calorie rich foods and obesity rates. Obviously ghrelin isn’t the only latent variable here to explain the association, but it may be part of a multivariate answer. Here, we explained the neurochemistry as to how ghrelin can be utilized to make you crave more food, even after satiety. There is a delicate balance that needs to be struck when it comes to these peptides, and any dietary alterations could change eating behaviors.

References:

  1. This is how much portion sizes have changed over time. https://spoonuniversity.com/lifestyle/this-is-how-much-portion-sizes-have-changed-over-time
  2. How sugar and fat trick the brain into wanting more food. https://www.scientificamerican.com/article/how-sugar-and-fat-trick-the-brain-into-wanting-more-food/
  3. Hedonic hunger and binge eating among women with eating disorders. doi: https://doi.org/10.1002/eat.22171
  4. Are We Slaves to Hedonic Hunger? https://psychcentral.com/lib/are-we-slaves-to-hedonic-hunger/
  5. Pathway detail. http://flipper.diff.org/app/pathways/Ghrelin
  6. Ghrelin and Leptin. https://www.news-medical.net/health/Ghrelin-and-Leptin.aspx
  7. Single night of sleep deprivation increased ghrelin levels and feelings of hunger in normal weight healthy men. https://pubmed.ncbi.nlm.nih.gov/18564298/
  8. Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults. doi: 10.1155/2012/530726
  9. Ghrelin at the interface of obesity and reward. doi: 10.1016/B978-0-12-407766-9.00013-4
  10. Structure and Physiological Actions of Ghrelin. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863518/
  11. Ghrelin – Physiological Functions and Regulation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819073/
  12. Ingested Medium-Chain Fatty Acids Are Directly Utilized for the Acyl Modification of Ghrelin. doi: https://doi.org/10.1210/en.2004-0695
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