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All About Neuropeptide Y (NPY) & How to Increase or Inhibit It

Written by Joe Cohen, BS | Reviewed by Selfhacked Science Team | Last updated:

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Neuropeptide Y (NPY) increases appetite & blood pressure but reduces anxiety & pain. Should you increase or decrease it? Find out here.

What is a Neuropeptide?

Neuropeptides are small molecules used by neurons to communicate with other neurons.

NPY is observed in many different parts of the hypothalamus, cerebral cortex, and spinal cord [1].

Neuropeptides usually travel in packets called vesicles. These vesicles travel in all different directions inside a neuron until a signal is given to release the neuropeptides. Once released, neuropeptides are received by other cells [2].

NPY is mostly found in sympathetic nerves, so NPY may take part in the sympathetic nervous system, which regulates fight-or-flight responses. However, NPY is also found elsewhere such as cardiac nonsympathetic and parasympathetic nerve fibers [1].

NPY Receptors

NPY has a similar structure with peptide YY (PYY) and pancreatic polypeptide (PP). All three peptides are considered to be in one family due to their similarities.

There are 5 receptors that carry out functions related to NPY (Y1-Y5).

  • The Y2 receptor is a receptor subtype found the most in the human brain and appears to be involved in activities such as the regulation of movement, heart, and blood, memory processing, circadian rhythms and release of other neurotransmitters [3].
  • The Y5 receptor is thought to be a receptor that is related to eating behavior in the hypothalamus. However, the Y5 receptor can also found in the human testis, spleen, and pancreas this can indicate that there may be other unknown functions of the Y5 receptor [4].

The Bad

Increases Appetite and Weight

Neuropeptide Y (NPY) is one of the big 4 hormones that determine weight.

NPY causes the creation of new fat cells and fat to build up in the belly, causing weight gain [5].

Studies of mice and monkeys show that repeated stress and a high-sugar diet stimulate the release of NPY and increase appetite for food [6, 7].

Cerebrospinal fluid Neuropeptide Y concentrations were significantly higher in many different stages of anorectic patients. These levels normalized in long-term weight-restored anorectic patients [8].

It’s likely that NPY does not initiate anorectic behavior, but less food intake in patients creates more NPY because the body needs more nutrition.

It has been found that Leptin, a hormone that monitors fat levels in the body, inhibits the production of NPY to reduce food intake [9].

Y5 receptor in the hypothalamus was found to be the cause of a direct relationship between food intake and NPY levels [10].

However, Y1 receptor deficient mice tend to be slightly more obese than regular mice. Also, the Y1 receptor deficient mice were characterized by damaged insulin secretion. This indicates that the Y1 receptor does not increase food intake but it increases the energy consumption [11].

Interestingly, Y2 receptor deleted mice specifically in the hypothalamus showed a significant increase in food intake but a significant decrease in body weight. This indicates that the Y2 receptor takes part in body weight regulation.

Increases Blood pressure

NPY is thought to increase the blood pressure by narrowing the blood vessels, or vasoconstriction. Increased level of the Y1 receptor, PYY, and NPY in an unconscious pig resulted in increased blood pressure in the abdomen [12].

Another study on unconscious pig suggests that Y2 receptor increases the blood pressure in the spleen [13].

A study on dogs has shown that NPY helps maintain the blood pressure during a septic shock, or a widespread infection that causes low blood pressure and organ failure [14].

Decreases Sexual Drive

A high dose of NPY to both male and female rats resulted in a decrease in sexual behavior. Experiments seem to suggest the reason for the decrease in sexual behavior is not from a reduction in sexual ability but from a reduction in sexual motivation [15].

A study in rats has shown that activation of the Y5 receptor resulted in less secretion of luteinizing hormone (LH), which is a hormone that triggers sexual motivational hormones both in male and female (testosterone) [16].

Cancer

NPY increases cancer risk by increasing angiogenesis [17].

Irregular Periods

Increased Neuropeptide Y activity may result in irregular period cycles [8].

The Good

Reduces Stress and Anxiety

NPY has a sedative effect on organisms [18].

NPY is increased by the stress response – specifically cortisol [19] and CRH – in order to ameliorate it. Y1 receptor inside amygdala is suggested to suppress anxiety. Also, the change in the Y1 receptor in the amygdala was independent to appetite which is mentioned to be related to the Y2 receptor in the hypothalamus.

NPY then goes on to lower all hormones in the stress pathway, including CRH, ACTH, and Cortisol. It also induces sleep [20].

NPY is released also by cold or heat stress [5, 21]. This is the main mechanism by which you feel relaxed and/or sleepy after a cold shower or sauna [22].

Higher levels of NPY may also protect against PTSD [23].

Green Berets were much less likely to suffer symptoms of PTSD after a week of grueling exercises that simulated being captured and interrogated by the enemy [24].

The elite soldiers produced more Neuropeptide Y in their blood than regular soldiers and it’s thought that this is what makes them more resilient [24].

Depression

People who have attempted suicide tend to have low NPY levels. People who attempted multiple suicides have the lowest NPY levels [25].

Reduces Pain

High NPY level was found to allow rats to endure more pain in a hot plate experiment [26].

Prevents Seizure

High level of NPY in hippocampus prevented and lessened the number and duration of seizures induced by kainic acid to rats [27].

It is suggested that the production of NPY is a human defense mechanism to prevent seizures [28].

Lessens Alcohol Consumption

Rats with fewer NPY receptors (Y1 and Y2) tend to consume a greater amount of alcohol and are less sensitive to the effects of alcohol [29, 30].

The Neutral

Shifts Circadian Rhythms

Small amounts of NPY injection into the suprachiasmatic region of the hypothalamus (SCN) tends to alter the circadian activity rhythm of hamsters housed in constant light. NPY injection 12 hours before the activity cycle (night) tends to advance the phase (make you wake earlier), while an injection at the onset of the 12-hour activity cycle (morning) tends to delay the phase (make you wake later) [31].

Stimulating Y2 receptors of hamsters resulted in phase advances of hamsters’ circadian rhythm (make you wake earlier) [32].

In hamsters, activation of Y5-like receptors resulted in inhibition of light-induced phase advances during the late night [33].

NPY Alters Memory Retention

In an animal model of stress, NPY injected in the hippocampus increased memory retention, but memory retention decreased when injected in the caudal portion of the hippocampus and amygdala [34].

What Increases NPY

What Decreases NPY

Genetics and NPY

  1. RS1468271 (NPY)
  2. RS16139 (NPY)
  3. RS5574 (NPY)

Want Better Ways to Improve Your Mood?

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About the Author

Joe Cohen, BS

Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.Frustrated by the lack of good information and tools, Joe decided to embark on a journey of self-experimentation and self-learning to improve his health--something that has since become known as “biohacking”. With thousands of experiments and pubmed articles under his belt, Joe founded SelfHacked, the resource that was missing when he needed it. SelfHacked now gets millions of monthly readers.Joe is a thriving entrepreneur, author and speaker. He is the CEO of SelfHacked, SelfDecode and LabTestAnalyzer.His mission is to help people gain access to the most up-to-date, unbiased, and science-based ways to optimize their health.
Joe has been studying health sciences for 17 years and has read over 30,000 PubMed articles. He's given consultations to over 1000 people who have sought his health advice. After completing the pre-med requirements at university, he founded SelfHacked because he wanted to make a big impact in improving global health. He's written hundreds of science posts, multiple books on improving health, and speaks at various health conferences. He's keen on building a brain-trust of top scientists who will improve the level of accuracy of health content on the web. He's also founded SelfDecode and LabTestAnalyzer, popular genetic and lab software tools to improve health.

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