Food Noise and GLP-1 Drugs: What Research Reveals About Motivation and Appetitive Drive

Patients on GLP-1s often report reduced “food noise,” but understanding of how these drugs affect motivation around food is incomplete. Wayne Pratt, PhD, shared with Psychiatric Times about his latest research on how glucagon-like peptide 1 (GLP-1) signaling may dampen the pro-feeding influence of reward circuitry in the brain.¹ Pratt noted that human functional magnetic resonance imaging studies showed that GLP-1 receptor agonists altered responses to food cues in reward-related regions, including parts of the striatum.² He characterized "food noise" as primarily a change in appetitive motivation (the drive to seek and work for food), while indicating that GLP-1 drugs appeared to influence both appetitive and consummatory motivation through homeostatic brainstem and hypothalamic systems as well as reward-related circuitry. He emphasized that food motivation is multidimensional, shaped by learned cues, accessibility, and effort, and that clinicians and patients need more evidence on the long-term benefits and adverse effects of GLP-1 drugs, including after discontinuation.

Psychiatric Times: Your lab found that GLP-1 receptor activation in the nucleus accumbens blunted binge-like feeding driven by mu-opioid stimulation. What might that suggest about why patients on GLP-1s report reduced "food noise"?

Wayne Pratt, PhD: My lab has long been interested in how the brain combines signals about physiological need, learned experience, and food reward to control food seeking and consumption. Part of our work has been to better understand how opioid signaling in brain reward regions affects eating and motivation. We and many other laboratories have shown that stimulating mu-opioid receptors in the rat nucleus accumbens strongly promotes eating, particularly of highly palatable foods, such as those high in sugar and fat hat are commonly consumed during binge episodes.

It is, of course, unlikely that mu-opioid receptor stimulation of the nucleus accumbens is equivalent to the “food noise” that humans report. However, our findings are consistent with the possibility that GLP-1 signaling can dampen some of the pro-feeding influence of reward circuitry. Importantly, human fMRI studies have shown that GLP-1 receptor agonists can alter responses to food cues in reward-related regions, including parts of the striatum. That does not mean our rat model is equivalent to human food noise, but it does suggest that both the basic and human literatures point toward a role for GLP-1 signaling within brain reward circuitry in dampening the motivational pull of food.

PT: Do you see food noise best understood as a change in appetitive motivation, consummatory motivation, or both?

Pratt: Appetitive motivation refers to the drive to seek out and work for access to food, whereas consummatory motivation occurs once food is obtained and is often measured by the amount of food consumed. “Food noise” seems to fall primarily into the former category, with people reporting that their thoughts often center on food. This can be driven by internal signals, such as hunger, or by external cues that have become associated with food and the desire for food.

One reason GLP-1 drugs are especially interesting is that they appear to influence both appetitive and consummatory motivation without, so far, producing the kinds of psychiatric problems that limited some earlier pharmacological strategies for treating obesity. GLP-1 signaling appears to impact homeostatic brain circuits, including brainstem and hypothalamic systems that monitor physiological state and contribute to satiety. But it can also influence reward-related circuitry involved in the motivational value of food; those systems normally interact. How hungry we are changes how rewarding food is, and learned food cues can motivate eating even when physiological need is relatively low.

So, although “food noise” seems most closely related to appetitive motivation, the current evidence suggests that GLP-1 drugs can influence both appetitive and consummatory aspects of food motivation. We are still working out how much of their clinical effect depends on each of those mechanisms, and how those effects are distributed across the brain and peripheral systems.

PT: What does the research suggest about how GLP-1s may be useful in binge eating disorder?

Pratt: There is emerging clinical evidence that suggests that GLP-1 receptor agonists may reduce binge-eating symptoms. But the evidence is not currently sufficient to consider GLP-1s effective for the treatment of binge eating disorder. My own basic research suggests that GLP-1 signaling can constrain strongly motivated palatable eating, but our rat paradigm was not a model of binge eating disorder itself.

PT: What aspect of this research would you highlight for the practicing psychiatric clinician?

Pratt: The main point I would highlight is that food motivation is multidimensional. It is shaped not only by hunger and reward, but also by learned cues, accessibility, and the amount of effort required to obtain food. One thing basic motivation research shows very clearly is that effort matters: if food is very easy to obtain, it is more likely to be consumed, whereas even modest increases in the effort required to get it can reduce food-seeking behavior. For a clinician, I think the broader lesson is that medications like GLP-1 drugs are acting in a system that is still strongly influenced by the environment and by learned behavior. The drug matters, but so does the context in which eating occurs.

PT: What are the next steps in your own research?

Pratt: One of the things GLP-1 research has underscored for me is that communication between the body and the brain is much more complicated than any single hormone or signaling system. There has been a renaissance of research focused on gut-brain interactions, such as how the gut microbiome affects broader health and brain function. In addition to the microbiome, the gut and other peripheral organs release signals that provide information about physiological state, and I am interested in understanding how those signals interact with brain systems involved in food motivation.

In our current work, we are asking how physiological signals that arise outside the brain may alter motivated behavior through actions on brain reward regions, particularly those that promote the eating of highly palatable foods. GLP-1 is one example, but it is only one of several signals that may influence these circuits. Ultimately, my students and I would like to better understand how these signals may interact with brain regions that promote overconsumption driven by palatability and by learned incentives associated with food.

PT: What questions would you most like the broader field to answer about GLP-1 drugs?

Pratt: I hope basic research continues to reveal how GLP-1 signaling interacts with both homeostatic systems that monitor physiological state and brain circuits involved in reward and food seeking. We know these drugs can have powerful effects on eating and body weight, but we still have a great deal to learn about which neural and peripheral mechanisms are most important and how they interact.

I also hope that clinical research continues to clarify the long-term benefits and potential adverse effects of these drugs, including what happens with prolonged treatment and after treatment is discontinued. We have a much better understanding of the efficacy of GLP-1 drugs over the first months and years of treatment than we do of their effects over many years. Ultimately, clinicians and patients need more evidence to help determine whether long-term use continues to yield lasting benefits that outweigh the potential risks.

Dr Pratt is a professor of psychology at Wake Forest University Professor. For more than 30 years, his students have sought to understand how the brain guides food-motivated behavior based on physiological need and experience. Using behavioral pharmacological methods in rodent models, his laboratory investigates how chemical signaling within the nucleus accumbens and connected brain regions helps regulate food seeking and consumption.

References

1. Pierce-Messick Z, Pratt WE. Glucagon-like peptide-1 receptors modulate the binge-like feeding induced by mu-opioid receptor stimulation of the nucleus accumbens in the rat. 2020;31(18):1283-1288.

2. van Bloemendaal L, IJzerman RG, Ten Kulve JS, et al. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans. Diabetes. 2014;63(12):4186-4196.