We all can recall the moments when it feels almost impossible to stop eating something tasty but incredibly unhealthy (like potato chips, for instance), even when we feel full. As it turns out, this is not just a curious trend – the phenomenon is interlinked with some fundamental appetite control mechanisms in our brain and may contribute substantially to the obesity epidemic.

Obesity has more than doubled since 1980: around 2 billion people are now overweight, and 600 million of those are obese.

Biologically, obesity occurs when calorie intake is greater than energy requirements during a long period of time, without acceptable energy expenditure. Excess calories are stored in the body as energy reserves (in the form of glycogen or fats) and they are used in the case of increased need for energy or when the body is starving. Therefore, if there is a proper balance between food intake and energy expenditure, obesity will not occur. The right balance can be hard to strike, though.

The amount of food we eat is controlled by survival and reward (also known as hedonic eating) mechanisms through metabolism of the body and our pleasure senses, like smell and taste. When specific neural signals in the brain are compromised, these two systems can become unbalanced, causing pleasure to take over, which can result in overeating and obesity.

New studies have improved energy homeostasis understanding by identifying neurohumoral mechanisms which deliver signals between the brain and gut in order to control food intake. The hypothalamus may be the major region with connections between the higher brain centers such as reward-related limbic regions, and the brainstem.

Moreover, the hypothalamus can modulate food intake and energy expenditure by integrating a number of peripheral signals. Gut hormones, such as CGRP (glucagon-like peptide-1peptide), peptide YY, pancreatic polypeptide, and ghrelin, are activated by acute food ingestion. Opposite, adipocytes cell signals such as leptin and insulin are involved in short- and long-term energy homeostasis.

Researchers from the Neuroscience Program in Substance Abuse (N-PISA) at Vanderbilt University say that the incidence of obesity can be reduced by understanding the mechanisms which lead to overeating.

They have conducted several studies in order to understand what can be the cause of overeating in obese and overweight people. Their studies showed that a high fat diet may cause people to eat more, even when they are feeling full. Eventually, this impairs the ability to control the caloric intake.

Their newest study reveals specific signaling pathway (insulin signaling) in the neuron circuits which may be the cause of overeating high fat foods for pleasure. This insulin-signaling pathway that controls movement, motivation and attention also determines the amount of high fat foods consumption. When this pathway is in some way disrupted, the body’s natural homeostatic mechanisms can be shifted in the favor of reward mechanisms and person will overeat high fat foods.

Researchers have found that there is a specific group of proteins involved in insulin signaling in the brain called Rapamycin Complex 2 (mTORC2). Study on mice showed that when the part of mTORC2 was taken out from their genetically altered brain cell, mice without the mTORC2 ate high-fat food excessively. However, this was not the case when a low fat food was provided. It has been also found that mice without appropriate mTORC2 function also had a smaller amount of the neurotransmitter dopamine in specific regions of the brain, and it is known that lower neural dopamine transmission in the brain is associated with obesity in humans and animals, and also in substance abuse. New studies will be based on restoring mTORC2 signaling in obese mice to see whether it leads them to eating a normal amount of food.

One study show that when exposed to the same high-fat diet, mice with lower dopamine receptor (D2 receptors) density in the specific part of the brain called the putamen show more weight gain compared to mice with higher D2 receptor density in the same region. Mice with higher levels of dopamine in brain show increased motivation to consume food.

Positron emission tomography (PET) studies found that obese adults compared to slim ones have less D2 receptor binding. D2 receptors in the striatum (component of the reward system in the brain) are reduced in morbidly obese individuals in proportion to their body mass. This can be also correlate with lower resting metabolism, which may contribute to overeating because of reduced inhibitory control.

Another study was conducted on rodents to examine the effect of diets rich in fat with or without additional sucrose. Fat-rich diet suppressed levels of ghrelin in serum without affecting leptin serum levels, but the combination of concentrated sucrose and high fat levels extremely reduced serum ghrelin and raised serum leptin levels in the fasted state. Mice reacted to sucrose in the drinking water with higher serum leptin (fasted state) and to all delicious diets with lower serum ghrelin levels. Clearly, the composition of diet has a serious effect on the level of various appetite-controlling hormones.

This brings us back to binge eating. The fact that people tend to overeat foods high in fats (and often high in carbs at the same time – think of junk food!) now has an explanation based on the way our brain functions. This pattern of eating appears to be very easy to establish, but not so easy to get rid of. And, for the time being, researchers cannot suggest an easy way out. Probably, it is easier to prevent the development of this pattern in the first place, particularly in children. Recent studies certainly do provide support for stricter regulations of the junk food market.

References

Dadalko, O., Niswender, K., & Galli, A. (2015). Impaired mTORC2 signaling in catecholaminergic neurons exaggerates high fat diet-induced hyperphagia Heliyon, 1 (1) DOI: 10.1016/j.heliyon.2015.e00025

Kocalis, H., Hagan, S., George, L., Turney, M., Siuta, M., Laryea, G., Morris, L., Muglia, L., Printz, R., Stanwood, G., & Niswender, K. (2014). Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis Molecular Metabolism, 3 (4), 394-407 DOI: 10.1016/j.molmet.2014.01.014

Stice E, Yokum S, Zald D, & Dagher A (2011). Dopamine-based reward circuitry responsivity, genetics, and overeating. Current topics in behavioral neurosciences, 6, 81-93 PMID: 21243471

Suzuki, K., Jayasena, C., & Bloom, S. (2012). Obesity and Appetite Control Experimental Diabetes Research, 2012, 1-19 DOI: 10.1155/2012/824305

Volkow, N., Wang, G., Telang, F., Fowler, J., Thanos, P., Logan, J., Alexoff, D., Ding, Y., Wong, C., Ma, Y., & Pradhan, K. (2008). Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors NeuroImage, 42 (4), 1537-1543 DOI: 10.1016/j.neuroimage.2008.06.002

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