Pathway

Curbs appetite

Appetite/satiety

The Satiety Signal

2 blends on this site modulate it.

Also searched as Appetite/satiety.

You want it strong: reliable satiety is how appetite and body weight stay in easy balance.

In depth

The signal that a meal is enough. Most published studies measure hunger and AgRP drive — satiety's absence — so their direction is read inverted here, and that is said openly.

What drives it

Fullness hormone (CCK) increases it.

PMC1382399 — Gut hormones such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) play a role as satiation factors. PMID 27875537 · PMC1382399

Stomach emptying reduces it.

Gastric distention, delayed gastric emptying ... are among mechanisms of fibers in decreasing hunger and prolongation of satiety. 10.1093/ajcn/nqab418. doi 10.1093/ajcn/nqab418

Appetite & sugar hormone increases it.

Drucker 2006, Cell Metab 3:153 — GLP-1 inhibits food intake and promotes satiety via central and gastric actions.

Lowers cortisol reduces it.

The PNAS title states something stronger than an association: leptin's hunger-suppressing effects ARE mediated by the hypothalamic-pituitary-adrenocortical axis. An obligatory middle step: stimulation of hunger requires an intervening endocrine step, namely activation of the HPA axis. Increased corticosterone then activates AgRP neurons to fully increase hunger. Low leptin does not reach the hunger neurons directly — it goes via the stress axis. And the receptor is on the cell: AgRP neurons express glucocorticoid receptors, and corticosterone regulates the expression of AgRP and neuropeptide Y. The loop runs both ways: all psychological OR physical stressors increase plasma ghrelin, ghrelin strongly activates c-fos in CRF-producing neurons, and mice lacking the ghrelin receptor failed to show normal stress-induced alterations of mood, feeding and metabolism. Corticosterone activates AgRP to drive hunger, so the HPA axis reduces satiety. Drawn inhibitory. doi 10.1073/pnas.1901795116 · PMC3282735

Gut barrier increases it.

Less a connection than an identity — the gut hormones ARE the appetite signal. Ghrelin, secreted by P/D1 cells in the gastric fundus, increases during fasting and rapidly decreases after eating, promoting feeding by stimulating AgRP neurons — described as the only known gastrointestinal hormone with appetite-stimulating effects. The satiety arm is equally concrete: enteroendocrine cells in the DUODENUM detect changes in intestinal tension and nutrient levels, releasing serotonin and cholecystokinin, which activate vagal afferents OR enter the bloodstream to mediate satiety. After eating, PYY and CCK inhibit appetite. Drawn from gut as this pathway is defined (barrier/signaling); the underlying literature is enteroendocrine and hormonal rather than microbial. doi 10.3389/fnut.2025.1484827 · PMC9040143

Opioid receptor signaling reduces it.

The pharmacology is anatomically local and the distinction it draws is the point: local administration of MOR antagonists such as naltrexone in the nucleus accumbens and amygdala reduces palatable diet intake. Not intake in general — palatable intake. The nucleus accumbens is described in this literature as the hedonic hotspot. MOR knockout mice show altered conditioned place preference for high-fat diet, and endogenous opioid peptides are described as governing palatable food intake. Why the sign is inhibitory onto this pathway: the pathway is satiety. Mu-opioid signaling makes palatable food more rewarding and drives consumption past fullness — so it opposes satiety. Rodent intracranial pharmacology; the human arm is the imaging correlation on the Mu-Opioid Signaling → Weight & Body Fat link. PMC10055773

Restores fullness signal increases it.

10.1530/JOE-14-0480 — drawn separately from the Leptin Signaling → Weight & Body Fat link on purpose, because the leptin-deficient mouse experiment separates them: the hyperphagia of the weight-reduced state is leptin-dependent while the compensatory drop in energy expenditure is not. In the human monogenic cases the presenting complaint is intense hunger and hyperphagia from childhood, and that is what replacement resolves first. doi 10.1530/JOE-14-0480

Appetite receptor signaling increases it.

NBK574539 — drawn separately from the Melanocortin (MC4R) Signaling → Weight & Body Fat link because the trials measured them separately: setmelanotide was associated with significant weight loss and reductions in hunger scores, and the phase 3 results support setmelanotide for the treatment of obesity and hyperphagia. Hyperphagia is a named co-primary indication, not a secondary observation. The endogenous physiology matches: POMC-derived melanocortin peptides reduce food intake.

Hunger hormone reduces it.

10.3389/fnins.2012.00024 — Ghrelin is the orexigenic signal, rising before meals. doi 10.3389/fnins.2012.00024

Feeding drive reduces it.

10.1371/journal.pone.0055217 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). doi 10.1371/journal.pone.0055217

Lowers wake signal reduces it.

10.3389/fphar.2013.00165 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). Verbatim: “Together, our data suggest that OX1R activity in the VTA facilitates food intake, potentially by counteracting postingestive negative feedback that would normally suppress feeding later in a meal”. doi 10.3389/fphar.2013.00165 · PMC5142223

Insulin sensitivity increases it.

10.3389/fendo.2014.00058 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). Verbatim: “Within the brain, insulin produces a net catabolic effect by reducing food intake and increasing energy expenditure; this is evidenced by the hypophagia and increased brown adipose tissue sympathetic nerve activity induced by central insulin infusion”. doi 10.3389/fendo.2014.00058 · PMID 22249812

Fasting insulin reduces it.

10.1523/jneurosci.22-20-09048.2002 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). doi 10.1523/jneurosci.22-20-09048.2002

Motivation reduces it.

10.3389/fnins.2020.572328 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). doi 10.3389/fnins.2020.572328

What it drives

It reduces Supports weight management.

Body-weight/appetite review 2008, J Clin Endocrinol Metab — satiation signals (CCK, GLP-1, gastric distension) terminate meals and, integrated with adiposity signals, regulate energy homeostasis; enhancing satiety lowers food intake and body weight. PMID 18987269

It increases Calm under stress.

Hunger is anxiolytic, and the circuit is named: selective activation of orexigenic AgRP neurons in the arcuate nucleus reduces aggression-related behaviors and inhibits anxiogenic neurons in the medial amygdala via inhibitory GABAergic projections. Hunger neurons project directly onto fear neurons and switch them off. Causal by CHEMOGENETICS: DREADDs selectively inhibited and stimulated AgRP neurons in Agrp-Cre mice, with open-field and elevated-plus-maze readouts. The circadian observation makes it physiology rather than pharmacology: anxiety levels were significantly reduced in the late light period, when mice have increased need for food and increased AgRP neuron firing. The animal gets less anxious as it gets hungrier, on its own schedule. This pathway is called satiety — fullness signaling — not hunger. All the evidence is about AgRP neurons, which are the hunger signal, i.e. the absence of satiety. So more satiety means less AgRP firing, and since AgRP activation is anxiolytic, more satiety means more anxiety. Bidirectional: severe anxiety impairs feeding via prefrontal inhibition of lateral-hypothalamic leptin-receptor neurons. Rodent only. doi 10.1038/s41398-019-0438-1 · PMC6408535

It increases Mood.

Drawn as a dysregulation signal rather than a direction, because that is what the imaging shows. Appetite change is a diagnostic criterion for major depression and it runs both ways — the paper title states the finding exactly: depression-related increases and decreases in appetite reveal dissociable patterns of aberrant activity in reward and interoceptive NEUROCIRCUITRY. And the control is what makes it interesting: the increase and decrease subgroups did not differ significantly in anhedonia severity — the authors deliberately excluded the food-and-drink items from the Snaith-Hamilton Pleasure Scale to avoid circularity — and the imaging still separated them. Two patients with the same diagnosis and the same anhedonia score, whose appetite moved opposite ways, have different brains. The circuit is the same one its sibling edge uses: lateral hypothalamus, ventral PALLIDUM, lateral HABENULA and the mesocorticolimbic targets, with dopamine, orexin, GABAergic and endocannabinoid signaling — the Dopamine → Mood (Positive Affect) link, the Endocannabinoid Signaling → Mood (Positive Affect) link and the GABA → Mood (Positive Affect) link are all drawn here. Cross-sectional human imaging, not an intervention. doi 10.1016/j.pnpbp.2019.109759 · PMC4818200

It increases Insulin sensitivity.

This link rests on the reviews of this outcome as a whole. No effect size specific to this arm has been reported, so it is shown at reduced weight. (from the reviews of this outcome). Sources: PMC9772276; PMC8160446; doi 10.1152/physrev.00031.2014. doi 10.1152/physrev.00031.2014 · PMC9772276

It increases Digestion.