What is a Neuropeptide?

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

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. (R)

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. (R)

The Bad

NPY 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. (R)

Studies of mice and monkeys show that repeated stress and a high-sugar diet stimulate the release of NPY and increase appetite for food. (R)

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. (R)

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 level in the body, inhibits production of NPY to reduce food intake. (R)

Y5 receptor in the hypothalamus was found to be the cause of direct relationship between food intake and NPY levels. (R)

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 Y1 receptor does not increase food intake but increases the energy consumption. (R)

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 Y2 receptor takes part in body weight regulation. (R)

NPY 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. (R)

Another study on unconscious pig suggests that Y2 receptor increases the blood pressure in the spleen. (R)

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. (R)

NPY 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. (R)

A study in rats has shown that an activation of 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). (R)

NPY and Cancer

NPY increases cancer risk by increasing angiogenesis. (R)

NPY and Irregular Periods

Increased Neuropeptide Y activity may result in irregular period cycles. (R)

The Good

NPY Reduces Stress and Anxiety

NPY has a sedative effect on organisms. (R)

NPY is increased by the stress response -specifically cortisol (R) 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. (R)

NPY is released also by cold or heat stress. (R, R2)  This is the main mechanism by which you feel relaxed and/or sleepy after a cold shower or sauna. (R)

Higher levels of NPY also protect against PTSD. (R)

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. (R)

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. (R)

NPY and Depression

People who have attempted suicide tend to have low NPY levels. People who attempted multiple suicides have the lowest NPY levels. (R)

NPY Reduces Pain

High NPY level was found to allow rats to endure more pain in a hot plate experiment. (R)

NPY Prevents Seizure

High level of NPY in hippocampus prevented and lessened the number and duration of seizures induced by kainic acid to rats. (R)

It is suggested that production of NPY is a human defense mechanism to prevent seizures. (R)

NPY 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. (R, R)

The Neutral

NPY 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). (R)

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

In hamsters, activation of Y5-like receptors resulted in inhibition of light-induced phase advances during the late night. (R)

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. (R)

What Increases NPY

What Decreases NPY

Genetics and NPY

SelfDecode, the best genetic analyzer, and gene interpreter, has 3 SNPs related to NPY.

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

Technical aspects of NPY

NPY is observed in many different parts of the hypothalamus, cerebral cortex, and spinal cord. (R)

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.

  • The Y1 receptor is readily found in the intestine, kidney, and heart. (R)
  • The Y2 receptor is a receptor subtype found the most in the human brain and appears to be involved in action such as the regulation of movement, heart, and blood, memory processing, circadian rhythms and release of other neurotransmitters. (R)
  • Y4 is found in the intestine, prostate, and pancreas. The Y4 receptor is also found in the brain stem. (R)
  • 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. (R)

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