How the Brain Constructs Hunger and Satiety
When you feel hunger, does your stomach signal the brain or does the brain signal the stomach? The answer is: Yes. As always, the machinations and communications between “systems” (gut-brain) is complicated and multi-faceted. Scientists have long wanted to understand “neurohormonal gut-brain signaling” as a means of developing “therapies for obesity and altered eating behavior.”
In “Mapping brain activity of gut-brain signaling to appetite and satiety in healthy adults: A systematic review and functional neuroimagining meta-analysis,” published in the journal of Neuroscience and Biobehavioral Reviews, scientists performed numerous meta-analyses with systematic assessments of corresponding brain regions through neuroimaging to determine patterns and identify appetite and satiety regulators.
When it came to appetite, results showed the “modulation of insula, amygdala, hippocampus, and orbifrontal cortex (OFC),” where responsible for hunger activation, whereas satiety regulation was “more associated with caudate nucleus, hypothalamus, thalamus putamen, anterior cingulate cortex in addition to the insula and OFC.”
As a result of the meta-analyses, scientists believe they have the “quantitative brain activation maps of neurohormonal gut-brain signaling in healthy-weight adults.” In other words, they are attempting to establish a baseline based on scans of healthy eaters. The hope is to use those maps to chart where the alterations in eating behaviors occur—and how to address the potentially misfiring signals.
The mapping of brain regions associated with appetite and satiety opens up new opportunities for understanding the neurologic underpinings of people with suboptimal patterns related to hunger and fullness.
The scientists discovered that data “combined from adult participants with a healthy weight and those living with obesity…have shown that the brain activity in people with obesity is significantly different from that in subjects with a healthy weight in several brain regions implicated in food reward, with greater activation in the obese group paired with hypoactivity in areas associated with homeostatic satiety.”
Understanding that satiety receptors—via the insula relay—are underperforming in some obese patients gives us a physiological understanding of overeating. Reward processing in the amygdala was also implicated, as well as other systems such as the hypothalamus and the caudate nucleus.
Unfortunately, this is just the beginning. As the researchers point out, “more work is needed to fully elucidate the complex interactions associated with the central regulation of appetite and satiety.”
Also published in the journal Neuroscience and Biobehavioral Reviews, the article—“The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review”—reports on results from “brain imaging studies focusing on how gut hormones influence brain function regulating appetite in healthy and obese subjects.”
The researchers refer to this as the “brain-gut axis,” the inderdependent neural systems in charge of our eating behaviors. Gherlin is the gut hormone that promotes hunger and activates systems “in the pre-frontal cortex (PFC), amygdala and insula.” Blood levels of “glucose, insulin, leptin, PYY, GLP-1 affect the same brain regions conversely.”
The hormonal peptides that set off the chain reaction related to hunger initiate in the gastrointestinal tract. “The two main families of gastrointestinal (GI) hormones are a)Appetite stimulators, such as gherlin…and b) Satiety stimulators” such as glucagon and leptin. The latter “signal the brain to decrease hunger and promote meal cessation.” Insulin also plays a major role in this process.
As in the previously mentioned study, neuroimaging helped demonstrate the systems involved, but could not account for, or even control for, the wide variances in individual participants/groups and studies.
Similarly, these researchers conclude that more studies are needed and that this approach can “enhance our understanding of the physiology of eating behavior and the pathophysiology of obesity and eating disorders.”
In the journal, Endocrinology and Metabolism Clinics of North America, Endocrinologists at the University of Pennsylvania, confirm that “Energy homeostatis is controlled mainly by neuronal circuits in the hypothalamus and brainstem, whereas reward and motivation aspects of eating behavior are controlled by neurons in limbic regions and the cerebral cortex.”
In the article, “Brain Regulation of Appetite and Satiety,” the researchers also conclude that understanding how “metabolic signals emanating from the gastrointestinal tract, adipose tissue, and other peripheral organs target the brain to regulate feeding” will go a long way toward helping patients with weight-related metabolic imbalances.
For those who want to a more in-depth exploration of the “hunger hormone,” the Journal of Clinical Investigation breaks it down in the article, “Gherlin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite.”
The researchers identify the “gut hormone ghrelin” as the primary hormone responsible for hunger and—interestingly—dopamine hits, or momentary pleasure spikes. The experiments showed that when rats were administered gherlin, feeding commenced, the intensity in proportion to the amount of the hormone delivered. Alternately, when given gherlin blockers, they adjusted their eating behavior accordingly and showed an “attenuated” response to fasting.
The researchers conclude that “the metabolic gut hormone ghrelin can directly affect” the “reward circuitry to modulate food intake” and may be “an important factor in the etiology of pathologies associated with food as well as drugs of abuse.”
Another related study shows the effect on eating behaviors after portions of the hypothalamus were damaged by lesions. In the journal Endocrine, Metabolic and Immune Disorders, the article, “Neuroendocrine Modulation of Food Intake and Eating Behavior” reported that when lesions appeared in the satiety center, located in the lateral (LH) and ventromedial hypothalamus (VMH), “lasting aphagia” was observed.
When these regions were stimulated the subjects experienced “hyperphagia” (abnormal increased appetite.) The researchers also investigated the role of oxytocin in “suppressing the reward circuitry in the brain,” which resulted in reduced food intake.
It is clear scientists are closing in understanding the full scope of the neuro-hormonal systems related to weight issues.
Once all of the systems and intricacies are understood, there is hope that medical treatments can be developed to support individuals with imbalances that contribute to weight disorders. Until then, we must ADD A LINE OR TWO HERE RELATED TO BOOK.
Studies cited:
Althubeati, S., Avery, A., Tench, C. R., Lobo, D. N., Salter, A., & Eldeghaidy, S. (2022). Mapping brain activity of gut-brain signaling to appetite and satiety in healthy adults: A systematic review and functional neuroimaging meta-analysis. Neuroscience and biobehavioral reviews, 136, 104603. https://doi.org/10.1016/j.neubiorev.2022.104603
Zanchi, D., Depoorter, A., Egloff, L., Haller, S., Mählmann, L., Lang, U. E., Drewe, J., Beglinger, C., Schmidt, A., & Borgwardt, S. (2017). The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review. Neuroscience and biobehavioral reviews, 80, 457–475. https://doi.org/10.1016/j.neubiorev.2017.06.013
Ahima, R. S., & Antwi, D. A. (2008). Brain regulation of appetite and satiety. Endocrinology and metabolism clinics of North America, 37(4), 811–823. https://doi.org/10.1016/j.ecl.2008.08.005
Abizaid, A., Liu, Z. W., Andrews, Z. B., Shanabrough, M., Borok, E., Elsworth, J. D., Roth, R. H., Sleeman, M. W., Picciotto, M. R., Tschöp, M. H., Gao, X. B., & Horvath, T. L. (2006). Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. The Journal of clinical investigation, 116(12), 3229–3239. https://doi.org/10.1172/JCI29867
Iovino, M., Messana, T., Lisco, G., Mariano, F., Giagulli, V. A., Guastamacchia, E., De Pergola, G., & Triggiani, V. (2022). Neuroendocrine modulation of food intake and eating behavior. Endocrine, metabolic & immune disorders drug targets, 10.2174/1871530322666220127114326. Advance online publication. https://doi.org/10.2174/1871530322666220127114326