To Eat or Not to Eat

June 19, 2018

Written by: Nitsan Goldstein

 

The feeling is all too familiar – you’re hungry one minute, start eating, and the next thing you know you are so full you can’t dream of eating another bite. Have you ever wondered why this happens? Our body and brain are in constant communication to help us eat when we need food and stop when we don’t. Food provides essential energy and nutrients to the cells in the body that allow them to perform the functions necessary for life. Hunger, therefore, is an extremely adaptive state that ensures that animals prioritize finding and eating food when the body is in need of energy. Overeating, however, is unhealthy and can lead to diseases such as obesity and diabetes. Therefore feeling “full,” or sated, is also an adaptive state that informs animals that they’ve had enough and should stop eating. This balance creates a cycle: as time passes without a meal, hunger accumulates to the point where food is consumed. At some point the feeling of fullness, or satiation, signals to the animal to stop eating, and the cycle begins again. The brain must combine signals from the rest of the body reflecting the energy state of cells in order to produce the appropriate behavior. Understanding how the brain performs this integration has been a major goal for neuroscientists for centuries, but research in this field has received increased attention recently due to the rapidly accelerating rates of obesity in children and adults in the United States.

 

One way in which the body can communicate its energy state to the brain is by releasing hormones that travel to the brain through the blood. As the time since the last meal increases, levels of the hormone ghrelin in the blood increase. Ghrelin is released from cells in the stomach when the stomach is empty. Ghrelin then travels to the brain where it relays the signal that the body is in need of energy. Once this signal is strong enough, the animal will eat, and levels of ghrelin are again reduced. Other hormones are released from the stomach and throughout the intestinal tract as food is consumed that have the opposite effect of ghrelin, signaling that enough food has been consumed to meet the energy and nutritional needs of the animal. Leptin is one of these hormones. Leptin is released from fat tissue when fat stores are high, indicating that eating should end. Other hormones or peptides are released by the gut to signal satiety such as cholecystokinin, amylin, and serotonin. Like leptin, these peptides act in the brain to reduce food intake, maintaining proper energy balance.

 

So where exactly in the brain are these signals acting to affect our eating patterns? Several regions in the brain are known to directly incorporate signals from the body and influence feeding behavior. There are even cell types within these regions that are known to specifically regulate food intake, either by causing an animal to eat, or by preventing them from eating. Many of these cell types are located in the hindbrain and the hypothalamus (See Figure 1). The hindbrain receives neural signals from the periphery through the vagus nerve. As the main connection between the gut and the brain, the vagus nerve is an important regulator of feeding and conveys information from the stomach and intestines to the hindbrain about what has been consumed. The hypothalamus receives information in two major ways: via direct neuronal projections from the hindbrain, and via hormones like leptin and ghrelin that can travel through the blood and act on the hypothalamus directly themselves, bypassing the hindbrain. For example, ghrelin binds directly to neurons in the hypothalamus and activates them. When active, they in turn activate other regions of the brain that cause feeding and inhibit regions of the brain that block feeding. In this way, the empty stomach can communicate hunger with regions in the brain in multiple ways that can influence an animal’s behavior and cause it to seek food and eat.

 

 

When the body is energy deficient, hunger drives us to eat. But why do we enjoy eating? Why does a cheeseburger sound so appealing at 4:00pm when you skipped lunch but revolting after a huge meal? The answers to these questions are still not fully understood, but clues may lie in the way the brain handles reward. The ventral tegmental area (VTA) is a region in the brain that is best known for its involvement in processing reward. Activity in this area is high during many rewarding behaviors like social interactions and sex. It turns out that ghrelin and leptin also act in the VTA. Studies suggest that ghrelin activates the VTA while leptin inhibits it. One theory about why eating is rewarding is that ghrelin, by activating the VTA, increases the rewarding value of food when you’re hungry and leptin, by inhibiting the VTA, decreases the rewarding value of food when you’re full. This can help explain why, under different circumstances, the same food can be either extremely rewarding or not at all appealing. The hormones released by the periphery are actually affecting the way the brain processes reward, changing our perception of food!

 

What happens when the balance between the drives to eat and not to eat is interrupted? One consequence of overeating is weight gain. Sometimes, this weight gain can reach the level of obesity, a condition where a person weighs more than is expected for their height. According to a recent study¹, one in three Americans are considered obese, which is about triple the obesity rate in the 1960s. Also striking, 1 in 6 American children and adolescents are obese (for more information about obesity, click here). In 1997, scientists discovered that some humans have a mutation in the Leptin gene². The mutation effectively removed a very important signal that tells the brain it’s time to stop eating, so people and animals with this mutation quickly become extremely obese (see Figure 2). Remarkably, leptin replacement therapy drastically improves the outcome of these patients, highlighting the important role of leptin in the regulation of body weight. The prevalence of leptin mutations, however, is very low. This means that the causes of most cases of obesity are not fully understood, and research geared toward understanding the variety of causes of obesity and how to best help people struggling to lose weight is becoming ever more important as rates of obesity continue to rise. Hopefully, more treatments will be forthcoming as scientists gain a greater appreciation of how the body works with the brain to control eating.

 

 

References

1. Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends in Obesity Among Adults in the United States, 2005 to 2014. JAMA 315(21):2284–2291 (2016). doi:10.1001/jama.2016.6458
2. Montague, CT et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387, 903 (1997).

 

Images

Cover image from Neuroscience News, Public domain. https://neurosciencenews.com/gut-brain-lifespan-8574/

Figure 2 from Wikimedia Commons. The original uploader was Bigplankton at English Wikipedia. Later versions were uploaded by Sunholm at en.wikipedia. Public domain. https://en.wikipedia.org/wiki/Leptin