“Happy Hunger Games! And may the odds be ever in your favor.”
— Suzanne Collins, The Hunger Games
Recently, the use of glucagon-like peptide-1 drugs, also known as GLP-1 agonists, like Ozempic for weight loss, has exploded. One of the mechanisms by which these drugs achieve their effect is to decrease the hunger drive. If we are what we eat, and we eat bad things, then these drugs help maintain better health by helping us eat less bad things and eat less things, in general. These medications work in part by making us less hungry by promoting satiety, slowing gastric emptying, and acting on areas of the brain responsible for appetite regulation.
And whilst effective, the exact mechanisms by which GLP-1 agonists act are not fully understood; a reality with implications regarding potential unintended consequences. That is why understanding how we are driven to consume certain foods is key in unraveling our individual food-health relationship.
This week’s review article defines the three known hunger processes, all of which are complicated and influenced by socioeconomic, cultural, psychological, and behavioral factors. The discussion begins by, importantly, differentiating between hunger:
“— the physiological impulse to eat that is triggered by starvation (acute energy deprivation) in order to maintain energy balance,”
and appetite, or hedonic hunger
“— food intake driven by pleasure rather than by metabolic necessity.”
- The analysis defines three distinct but highly interconnected forms of hunger:
- homeostatichedonic
- microbiota driven.
- All forms of hunger involve gut-brain axis crosstalk.
- Homeostatic hunger is triggered by food deprivation.
- Hedonic hunger or appetite occurs in the absence of any acute, physiologic, caloric, or energy needs.
- There is significant evidence that our gut microbiota influences our innate hunger circuitry.
The Caveat:
Homeostatic hunger is likely the oldest hunger mechanism and specifically involves the hypothalamus-gut axis. This pathway involves sensory signals originating mainly from the G.I. tract and is triggered by food deprivation. An empty stomach, via the vagus nerve, causes the secretion of ghrelin, also known as the appetite hormone or hunger gremlin. This information is delivered to the hypothalamus, stimulating the release of dopamine and reinforcing the hunger signal. The information – we are hungry – is relayed and activates an area of the brain that includes specific neurons, known as AgRP (agouti-related peptide) neurons, that turn off when we experience food through vision, smell, or taste. This, of course, gives credence to the chefs’ claim that we eat with our eyes first! Homeostatic hunger is also triggered via hypoglycemia, or low blood sugar, again via hypothalamic processes.
Homeostatic hunger can be turned off by physical distention of the stomach as well as the presence of specific amino and fatty acids. The act of gastric emptying also aids in reducing the cravings of the hunger gremlins. The transition of food from the stomach into the proximal small intestine is accompanied by the secretion of several different hormones, including GLP-1, cholecystokinin, and peptide YY, all of which act to send signals to the brain that inhibit homeostatic hunger.
Hedonic hunger or appetite is “characterized by a desire to eat in the absence of acute caloric need.” In this setting, our desire overrides any automatic hypothalamic control of energy balance. This response can be strongly influenced by emotions such as anger, fear, sadness, and depression in individual ways. Those particular emotions are generally associated with a craving for sweeties. Since we have an innate bias for foods that are salty, fatty, and sweet, the consumption of these foods positively triggers the brain’s reward system. In addition to the dopaminergic reward center, consumption of these foods involves endogenous cannabinoids, endogenous opioids, and orexin signaling pathways.
Simply put, eating these kinds of foods makes us feel better. The desire for these foods can also be heavily influenced by socioeconomic factors, cultural beliefs, and religion. Suffice it to say, the routes by which hedonic hunger is turned on and off are multifactorial, extremely complex, and involve learning, cognition, and memory, as well as the other paths mentioned.
The final hunger gremlin involves the gut microbiome. It is currently well established that the gut microbiota can influence hunger-controlling hormones such as ghrelin, leptin, and insulin, which are produced within the gut, adipose tissue, and the pancreas. It is also known that obesity is associated with increased gut permeability, which allows a greater influx of compounds produced by the gut microbiota to communicate with host tissues. Greater gut microbiome diversity (a condition associated with better gut health) is associated with hunger inhibition through mechanisms involving increased synthesis of GLP-1 and peptide YY. There is also evidence that gut bacteria can modulate hunger by influencing AgRP neurons. Some of these effects may be related to the production of short-chain fatty acids such as butyrate, propionate, and acetate, which are the result of fermentation by the bacteria within the human gut, which also impact the production of insulin and leptin.
Interestingly, the gut microbiome also produces gamma-aminobutyric acid (GABA) when we consume glutamate. Glutamate is the substance responsible for our perception of the umami flavor or savoriness of a food or dish. It is a compound found in food that makes it yummy.
GABA is a non-protein amino acid that is the primary inhibitory neurotransmitter in the central nervous system. It plays a crucial role in reducing neuronal excitability throughout the nervous system and helps maintain the balance of neuronal activity in the central nervous system. Its proper functioning is essential for normal brain activity and overall neurological health and is a critical molecule in maintaining vibrant gut-brain communication.
Considering that obesity-related medical care costs the United States an estimated $173 billion annually, understanding what drives us to choose the items and quantities of things we consume is a critical link in better understanding our individual food-health relationship in all its “multidimensional, complex, and still not completely defined” ways.
The Study:
Additional resources:
Alonso-Alonso M, Woods SC, Pelchat M, et al. Food reward system: current perspectives and future research needs. Nutr Rev 2015; 73: 296-307.
Cani PD, Lecourt E, Dewulf EM, et al. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr 2009; 90: 1236-43.
Gutjar S, Dalenberg JR, de Graaf C, et al. What reported food-evoked emotions may add: a model to predict consumer food choice. Food Qual Prefer 2015; 45:140-8.
Meule A, Vögele C. The psychology of eating. Front Psychol 2013; 4: 215.
Parnell JA, Reimer RA. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr 2009; 89: 1751-9.
Salerno A, Laran J, Janiszewski C. Hedonic eating goals and emotion: when sadness decreases the desire to indulge. J Consum Res 2014; 41: 135-51.