Regulating Food Intake via the Gut-Brain Axis

Calories are essential for maintaining the structure and function of the body. Of course, ensuring the correct calorie balance is necessary to sustain energy for daily processes and activity, but also prevent excessive weight gain. Calorie needs are based on sex, age, body composition, metabolic rate, and physical activity patterns.

But how do we know when to start eating? Why do we feel hunger? And how do we know when to stop eating due to feelings of fullness or satiety? Surprisingly, our brain receives signals are derived from the gastrointestinal (GI) tract and the pancreas. These signals, in the form of hormones, peptides, and neurons, work synergistically to initiate eating (through hunger feelings) and the cessation of eating (through satiety feelings). Thus, the link between the gut and the brain is called the gut-brain axis.

Hunger Feelings

Feelings of hunger begin to develop when the GI tract has digested and absorbed the calories and nutrients from the prior meal. Several processes are involved in initiating hunger. First, the lack of food in the GI tract stimulates the release of ghrelin (the hunger hormone discovered in 1999) from the stomach which acts on the brain to stimulate food intake. In the brain, ghrelin stimulates neurons in the hypothalamus, specifically agouti-related peptide and neuropeptide Y while inhibiting proopiomelanocortin (POMC), to cause downstream effects. Not only do these nerve signals stimulate appetite they also cause growth hormone release from the pituitary as well as inhibits insulin release from the pancreas. Low blood insulin concentrations activate gluconeogenesis - which is the mechanism of forming new glucose in the liver and kidney from other substrates – to enter the blood and be used by other tissues. Gluconeogenesis is important during fasting because it generates the required amount of glucose that the brain requires to survive. Ghrelin also reduces energy expenditure by inhibiting POMC as if the body is anticipating an extended period without food intake. Concentrations of the “hunger hormone” are highest during a long fast and drop to basal levels within one hour of food consumption.

Satiety Feelings

During food intake, two separate mechanisms contribute to the cessation of eating. First, the presence of food in the GI tract increases gut motility to move the contents through the system. The GI tract expands because of the weight and bulkiness of food. GI tract expansion elicits neuronal signals to the central nervous system, which will provide feedback mechanisms to promote satiety when adequate food has been consumed. Second, nutrients are digested and absorbed into the blood. Blood glucose concentrations increase, provided the meal contained some type of carbohydrate. Elevated glucose, along with other peptides that are released from the GI tract, cause insulin to rise. Insulin is necessary for glucose to enter certain tissues (the brain does not require insulin) and be used to generate energy. However, insulin is “sensed” in the brain and does play a role in satiety. Finally, specific nutrients can bind to enteroendocrine cells – or cells that line the GI tract such as K and L cells – to cause the release of additional satiety signals. These signals, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are also sensed in the brain to elicit satiety (Figure 2). Interestingly, GLP-1 agonists (e.g., Ozempic, Victoza, Trulicity) are all GLP-1 agonists – meaning they mimic GLP-1 actions in the brain (and other tissues to regulate blood glucose) to increase satiety. As such, one of the side effects of these injectable drugs is weight loss. Each of these mechanisms work together to cease eating.

Of course, we cannot rule out the emotions related to starting and stopping the act of eating. For example, smelling chocolate chip cookies baking in the oven may remind you of your grandmother’s house during childhood when she would make those same cookies every time you visited. However, eating is more than just emotion with a strong physiological drive. The balance of what, when, and how we consume food is key in maintaining a healthy body.