Neuropeptide Y – or just “NPY” for short – is a compound with a wide variety of potential effects on the body and brain. It has been suggested to play a key role in stress, pain, and anxiety, among many other interesting functions. However, its mechanisms of action appear to be quite complex, and science is still actively figuring out exactly how this neuropeptide might be related to various aspects of physiological and psychological health. Read on to learn more about what NPY is, how it might work, some of its purported roles throughout the body, and some of the lifestyle and other factors that may influence a person’s levels of this interesting compound!
What is a Neuropeptide?
Neuropeptides are protein-like molecules (“peptides”) used by neurons to communicate with other neurons. In this respect, they are quite similar in function to neurotransmitters (such as serotonin, dopamine, and norepinephrine), in that they act as the “chemical messengers” that allow one neuron to influence the activity of another.
Also similar to neurotransmitters, neuropeptides travel in “packets” called vesicles. These vesicles are packed and moved around (trafficked) through a neuron until a particular signal is given to release them. Once released, neuropeptides drift throughout the synapse or the brain until they are received by another cell, where they exert their effect on neural activity [1].
In other words, both neurotransmitters and neuropeptides are part of what allows neurons to “communicate” with each other in order to pass along signals and process information – which is obviously what allows the brain to function as a coherent whole, rather than just being a bunch of isolated cells.
However, there are two main differences between neuropeptides and neurotransmitters. The first difference is that neuropeptides are generally much larger molecules than neurotransmitters. The second – and more important – difference is that neurotransmitters are relatively fast-acting, and produce a very rapid and short-lived response in the neuron that receives them; in contrast, neuropeptides are much slower-acting, and produce significantly longer or more sustained effects on the receiving neuron [2, 3].
It is also important to note that the label “neuropeptide” is contextual: for example, there are many hormones that act on the brain, which is why they are sometimes referred to as neuropeptides or neuropeptide hormones. In other words, these two labels are not mutually exclusive: a compound can be referred to as a hormone (or any other type of compound) when it is acting on the body in general, and can also be referred to as a neuropeptide when discussing its actions on the brain, specifically.
A few examples of neuropeptides include [4]:
- Melatonin
- Oxytocin
- Vasopressin
- Thyroid-stimulating hormone (TSH)
What Is Neuropeptide Y?
Neuropeptide Y – or just “NPY” for short – is a specific neuropeptide that has been found in many different parts of the brain, including the hypothalamus, cerebral cortex, and spinal cord [5].
While NPY appears to be present throughout many regions of the brain, NPY is predominantly found throughout the sympathetic nervous system. This has led some researchers to speculate that NPY’s main role might pertain to the primary functions of the sympathetic nervous system, such as the “fight-or-flight” response [5].
However, NPY is also found elsewhere, such as the cardiac non-sympathetic and parasympathetic nerve fibers [5]. This probably indicates that NPY has a number of different key roles – and which one it plays at any given time might depend on exactly where it is in the body and brain.
In any case, it is clear that much more research will be needed to tease out all the different functions of NPY throughout the brain and nervous system as a whole.
NPY Receptors
NPY shares a similar molecular structure with other neuropeptides, such as peptide YY (PYY) and pancreatic polypeptide (PP) [6]. All three peptides are therefore considered to belong to a single “family” of neuropeptides due to their overall similarities.
There are 5 specific receptor subtypes that carry out functions related to NPY, called ‘Y1’ through ‘Y5’.
However, relatively little is currently known about the subtle differences that exist among these five specific subtypes of receptors. Much of what is currently known pertains to the ‘Y2’ and ‘Y5’ subtypes:
- The Y2 receptor is a receptor subtype found in the highest concentration in the human brain, and appears to be involved in a diverse range of activities including the regulation of movement, heart, and blood, memory processing, circadian rhythms and release of other neurotransmitters [7].
- The Y5 receptor is a receptor subtype commonly found throughout the hypothalamus, which is believed to be related to eating behavior. However, the Y5 receptor can also be found in the human testes, spleen, and pancreas; this suggests that there are probably many other undiscovered functions of the Y5 receptor [8].
Purported Effects of NPY
In the sections below, we will discuss what the latest science currently has to say about some of the potential effects of NPY, and its wider roles in physiological and/or psychological health.
However, it is important to note that while some of these preliminary findings may seem to shed some light on the mechanisms and effects of NPY, the evidence so far is still too weak as a whole to come to any definitive conclusions about its effects on the body and brain, or how relevant it might be when it comes to any specific aspects of health or health conditions.
In other words, these purported effects of NPY should be considered as currently having insufficient evidence to support them – and much more research will still be needed to figure out exactly what effects NPY might have in humans.
With that in mind, let’s continue on to see what the science currently says about this interesting neuropeptide!
INSUFFICIENT EVIDENCE:
1) May Affect Stress and Anxiety
Some early evidence from an animal study suggests that NPY may have “sedative” and “anxiolytic” (anti-anxiety) effects that may partially counteract some of the physiological effects of elevated stress [9, 10].
This link is further backed up by some other preliminary reports that NPY levels often increase during the stress response. This increase in NPY may be stimulated by increased levels of the stress-related neuropeptide hormones cortisol and corticotropin-releasing hormone (CRH), which higher NPY levels would partially counteract [11].
According to some researchers, these stress-related increases in NPY may, in turn, counteract a number of other hormones involved in the stress pathway, including CRH, ACTH, and cortisol. NPY may also induce sleep [10].
The release of NPY has also been associated with exposure to cold or heat stress [12, 13]. This has led some researchers to speculate that NPY may be one of the mechanisms involved in the relaxing and sleep-inducing effects of cold showers or saunas [14].
Finally, higher levels of NPY have also been reported to potentially protect against the development of PTSD [15].
For example, one study reported that highly-trained elite soldiers from special-forces units were significantly less likely to suffer from PTSD symptoms compared to more novice or less-experienced soldiers – and that at least part of this difference might be due to elevated levels of NPY in the more stress-resilient group of veteran soldiers [16].
However, much more research in humans will still be needed to flesh out these early findings, and confirm the extent of NPY’s potential involvement in protecting against the long-term consequences of extreme stress.
2) May Influence Appetite and Body Weight
Neuropeptide Y (NPY) is currently believed to be one of the “big four” hormones that determine weight (the three others being insulin, leptin, and cortisol).
However, its specific roles in affecting weight are still being actively studied and discovered.
According to some researchers, NPY may exert an influence on body weight by stimulating the creation of new fat cells, and promoting the build-up of fat stores (especially in the abdominal region) [12].
Studies of mice and monkeys have reported that repeated stress and a high-sugar diet may each be factors that can stimulate the release of NPY, and in turn increase appetite for food [17, 18].
Studies in eating disorder patients have reported that the levels of NPY in the cerebrospinal fluid are often significantly elevated in anorexia patients – and that these levels often return back to a more normal “baseline” level once the anorexia is treated, and the patient returns to a healthy overall body weight [19]. The authors of this study suggest that although it’s not likely that NPY itself is responsible for initiating anorexic behavior, the restriction of food intake in anorexic patients stimulates the production of NPY.
One study has reported that leptin, a hormone that monitors fat levels in the body, may reduce food intake by inhibiting the production of NPY [20].
According to one study, the ‘Y5’ receptor in the hypothalamus may be involved in the relationship between NPY levels and overall food intake [21].
However, an animal study reported that ‘Y1’ receptor-deficient mice tend to be slightly more obese than regular mice. Additionally, the Y1-deficient mice were characterized by damaged insulin secretion. This finding suggests that while the Y1 receptor may not increase food intake directly, it may still play a role in increasing overall energy consumption [22].
3) May Be Involved In Depression
According to one preliminary study, people who have attempted suicide tend to have relatively lower NPY levels than average; in fact, people who attempted multiple suicides were reported to have the lowest NPY levels of all [23].
While this evidence is suggestive of some kind of connection between the two, it is still too early to conclude for certain whether NPY plays a direct role in depression or suicide until much more follow-up research is done to confirm this.
4) May Be Involved In Menstruation
According to one early study, elevated NPY levels may contribute to irregular menstruation cycles (irregular periods) in patients with eating disorders [19].
However, this finding should be taken with a grain of salt until more research is done, as there are many different factors (such as severe nutritional deficiencies from restricted eating) that could be causing these symptoms in eating disorder patients, and it’s unclear to what extent NPY itself might be directly responsible for these.
5) May Be Involved In Seizures
One preliminary animal study reported that rats with higher levels of NPY appeared to be less susceptible to seizures induced by kainic acid – specifically, these high-NPY rats experienced fewer overall seizures, and the duration of the seizures they did experience also tended to be shorter in duration [24].
Based in part on these early findings, some other researchers have proposed that NPY may protect against seizures in humans. This may be due to the ability of Y1 and Y2 receptors to suppress the excessive release of glutamate – one of the brain’s main excitatory neurotransmitters – in certain brain regions, such as the hippocampus [25].
However, this research is still in a very early stage, and NPY has not been officially recognized as a potential mechanism for the medical treatment of seizures at this time, and much more research will still be needed to elucidate its precise role.
ANIMAL AND CELL STUDIES ONLY:
The potential effects of NPY discussed below have so far only been observed in studies in animals or in cells, and have not been directly confirmed by any studies in humans so far.
Therefore, these reports should be taken only as suggestive directions for future research work, and are otherwise strictly provisional until corresponding research in human populations is performed.
6) May Regulate The Circadian Rhythm
According to a few early animal studies, NPY may play a potential role in helping to “set” or “adjust” the circadian rhythm, which is the body’s “master clock” that in turn regulates a wide variety of important behaviors, such as appetite and the sleep cycle.
For example, injecting small amounts of NPY into the suprachiasmatic nucleus (SCN) of the hypothalamus has been reported to “shift” the circadian rhythm in a few studies in hamsters. Injections of NPY before nighttime tended to shorten the overall duration of sleep, whereas an injection in the early morning caused the animals to stay awake longer [26].
Relatedly, stimulation of ‘Y2’ and ‘Y5’ NPY receptors caused similar shifts in the circadian rhythm in other studies in hamsters [27, 28].
However, these mechanisms may differ between hamsters and humans, and similar effects have not been directly observed in any human studies yet.
7) May Affect Alcohol Consumption
According to some preliminary studies in animals, rats with relatively lower numbers of ‘Y1’ and ‘Y2’ NPY receptors were reported to consume a greater amount of alcohol compared to rats with greater numbers of these receptors. Additionally, rats with fewer of these NPY receptors may be less sensitive to the effects of alcohol overall – which could be one of the factors driving greater alcohol consumption in these animals (since they would need a greater amount of alcohol to feel the same effects) [29, 30].
While these early findings suggest that NPY (and/or its receptors) may play some general role in alcohol consumption and/or the sensitivity to its effects, this link has not been directly investigated in humans yet – so more research will be needed to know for sure.
8) May Affect Memory Retention
According to one animal study, NPY may play a role in the storage (“retention” or “consolidation”) of memory – however, the results suggest a nuanced and potentially complex relationship.
In this study, NPY injected into the hippocampus was reported to increase memory retention after an injection of amnesia-causing drugs (scopolamine and anisomycin). However, memory retention decreased when NPY was injected into the caudal (rear) portion of the hippocampus and amygdala [31]. This contrasting pattern of effects suggests that the exact effects of NPY on memory may be dependent on exactly where in the brain it is acting at any given time.
However, this preliminary finding has also not been followed-up on by any corresponding human studies yet, so its relevance to humans remains unknown at present.
Another major limitation to note here is that the above animal study only reported that NPY “improved” memory in response to other drugs that directly impair memory – which doesn’t necessarily mean that NPY would have any effect on memory under normal conditions.
9) May Affect Pain
According to one animal study, rats with higher levels of NPY were better able to endure pain from exposure to a “hot plate” stimulus [32].
However, apart from this one early study in animals, this link has yet to be directly demonstrated in humans.
10) May Influence Blood Pressure
NPY is believed to increase blood pressure by narrowing the blood vessels (vasoconstriction). According to a few preliminary animal studies, increased numbers of Y1 and Y2 receptors, as well as higher levels of PYY and NPY, may be associated with elevated blood pressure [33, 34].
Another animal study (in dogs) has reported that NPY may help maintain blood pressure during septic shock (a widespread infection that causes low blood pressure and organ failure) [35].
However, all of these findings have only been reported in animals so far, and their potential relevance to humans will have to be confirmed by additional studies.
11) May Influence Sexual Drive
Some early evidence from animal studies suggests that NPY may play a role in sexual drive and behavior.
For example, one animal study reported that a high dose of NPY caused an overall suppression of sexual behavior in both male and female rats. The authors of this study interpreted these results as a reduction in sexual motivation, rather than a decrease in sexual performance per se [36].
Additionally, another animal study has reported that activation of the Y5 receptor may result in less secretion of luteinizing hormone (LH), a hormone that stimulates sexual drive by increasing the levels of other sex-related hormones (such as testosterone) in both male and female rats [37].
One again, however, these findings have only been reported in animal models, and it remains to be seen whether similar effects might be seen in humans as well.
12) May Be Involved in Cancer
According to some very preliminary evidence (primarily from in vitro cell studies), NPY may play a role in the development of cancer – specifically, by stimulating angiogenesis (the growth of new blood vessels that supply tumor cells with access to the blood supply, which enables them to grow larger) [38].
However, a direct link between NPY and the development of cancer has not been demonstrated in humans yet, and more research would be needed to confirm these initial findings.
Factors That May Influence NPY Levels
In addition to some of the early research regarding the role and effects of NPY on the body and brain, there has also been some research done on various lifestyle, genetic, dietary, and other factors that may influence the overall levels of NPY.
However, nearly all of these factors have only been investigated in studies on animals or in cells, and so their relevance to NPY levels in humans remains largely unknown.
Because of this, we are not making any specific recommendations regarding the factors listed below – this information is presented for informational purposes only.
As always, if you think that you may be suffering from a health condition or symptom that may involve NPY, talk to your doctor so that you can obtain an official diagnosis, as well as develop a comprehensive and safe treatment plan for addressing your specific health needs.
Factors That May Increase NPY Levels
- Cortisol and dexamethasone [39]
- Strenuous exercise [40]
- “Adaptogens,” such as Rhodiola [40]
- Exposure to cold [40]
- Controlled exposure to “heat stress,” such as by taking a sauna [12, 13]
- Psychological stress [40]
- Nicotine withdrawal [41]
Factors That May Decrease NPY Levels
Genetic Factors That May Affect NPY Levels or Function
A number of specific genetic variants have been identified which have been reported to potentially influence the levels of NPY that an individual produces, or which may affect the way that NPY functions throughout the body, brain, and nervous system.
Unsurprisingly, all of the following NPY-related SNPs are found in the (appropriately-named) NPY gene:
