Feeding drive
Neuropeptide Y (NPY)↓
Also searched as Neuropeptide Y (NPY).
The Balance here is not Visible in the Arrows — only the upside is shown — it lowers anxiety and restrains crf, which is why it is described as the brain's own stress buffer. The cost is not Among the Arrows Shown: npy is also one of the strongest appetite drivers known, and rises with restriction — which is part of why aggressive dieting is hard to hold. Too few consequences are shown to judge this one; read it as incomplete.
In depth
Neuropeptide Y — a potent appetite-and-energy signal that drives feeding and body-weight gain.
What drives it
Energy sensing increases it.
Hypothalamic-AMPK/NPY study 2016, Autophagy — constitutively active AMPK in the medial hypothalamus increases orexigenic NPY/AgRP expression, driving food intake. doi 10.1080/15548627.2016.1215382
What it drives
It increases Supports weight management.
Stanley 1986, Peptides — chronic hypothalamic neuropeptide Y injection overrides satiety, driving hyperphagia and body-weight/fat gain. PMID 3470711. Two mechanisms at once, which is why these neurons are so powerful: NPY/AgRP neurons — found only in the hypothalamic arcuate nucleus — stimulate feeding both by raising NPY signaling and by releasing AgRP, an endogenous melanocortin-3/4 receptor antagonist that removes the satiety brake. They push the accelerator and cut the brake cable in the same action. And they move both sides of the energy equation: when activated they stimulate food intake and reduce energy expenditure. Regulation is explicit: inhibited by insulin and leptin, activated by ghrelin — so a fall in leptin or insulin signaling activates them, which is why fasting, uncontrolled diabetes and genetic leptin deficiency all raise food intake. The controlled experiment that changes the advice: in pair-fed mice — matched for caloric intake and weight gain — high-fat diet still produced a significant increase in AgRP neuronal spiking. The authors conclude diet composition may be more important than either calorie intake OR body weight for electrically remodeling these neurons. Even brief high-fat feeding caused persistent activation, and leptin-insensitivity was not a prerequisite for the raised firing rate — the circuit changes before leptin resistance appears. these neurons are not essential for all feeding — they are stated to be not required for the feeding response to glucoprivation. PMID 3470711
It reduces Calm under stress.
10.1038/npp.1993.35 — But microinjection into the central nucleus of the amygdala did not increase food intake while still acting on anxiety — the anxiolytic action is anatomically separable from the feeding action, mediated by Y1 receptors in the amygdala rather than the hypothalamic mechanism that drives intake (Neuropsychopharmacology, npp199335). Human genetics: a single-nucleotide polymorphism in the NPY promoter, rs16147, decreases NPY expression and correlates with enhanced anxiety traits — less peptide, more anxiety, in people. Human biomarker: adults with PTSD have lower NPY in cerebrospinal fluid. Human intervention, stated cautiously: a clinical trial concluded that intranasal NPY may be associated with anxiolytic effects in adults with PTSD (Sayed 2018), with a follow-up trial ongoing — the hedge is the authors' own and is kept. the anatomical and receptor work is rodent; the genetics and CSF findings are human. doi 10.1038/npp.1993.35
It reduces Alertness chemical.
NPY is colocalized and co-released with norepinephrine in most sympathetic nerves and in brainstem noradrenergic cell groups — and it inhibits the transmitter it travels with. NPY inhibits the firing rate of locus coeruleus neurons and inhibits release of norepinephrine through the presynaptic Y2 receptor, and potentiates norepinephrine's own inhibitory effect on LC neurons via Y2. A built-in brake on the system that carries it. The release rule is a duration rule, which matters for a stress atlas: NPY co-stored with norepinephrine is preferentially released by intense and prolonged sympathetic activation — it is not a first-response signal, it arrives when the alarm has been running a while. The same co-transmission is not benign everywhere: in 78 patients after ST-elevation myocardial infarction, higher venous NPY predicted sustained VT or VF despite beta-blockade, with a threshold of 27.3 pg/mL (sensitivity 0.83, specificity 0.71) — the peptide beta-blockers do not touch (PMC3602986; PMC4641560; doi 10.1093/eurheartj/ehz852). A peri-LC NPY population exerts inhibitory control over the LC via NPY-Y1 receptor signaling, giving bidirectional control of anxiety-like behavior in naive animals. Stress recruits the brake: stressful experiences recruit peri-LC NPY neurons with local NPY release measured in vivo, and enhanced peri-LC NPY activity curbs anxiety after stress. The authors state they establish a causal role — this is no longer inference from receptor pharmacology. doi 10.1093/eurheartj/ehz852 · PMC3602986
It reduces Stress-relapse axis.
10.3389/fnins.2020.629003 — ,NPY inhibits firing rate of the locus coeruleus, inhibits release of crf and norepinephrine, and is anxiolytic in a variety of animal models. Receptor coupling is inhibitory: Y receptors associate with Gi/o proteins and inhibit adenylyl cyclase and cAMP accumulation. doi 10.3389/fnins.2020.629003
It reduces Curbs appetite.
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
It increases The Stress Veto.
The sixth and least-known veto on fat release, and the one stress opens. Alongside lactate, short-chain fatty acids, long-chain fatty acids, succinate and nicotinic acid, neuropeptide y acts through its own Gi-coupled receptor on the fat cell: 'many of lipolysis' regulators act on the pro-lipolytic PKA pathway, which is typically activated by catecholamines and can be inhibited by different factors upon binding to their respective Gi-coupled receptors' (doi 10.3389/fphys.2022.826314). Why it matters more than the other five for a real person: this ligand rises with stress, and it is released alongside the very epinephrine that is supposed to be driving release. The accelerator and this brake arrive together. doi 10.3389/fphys.2022.826314
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.