Neuropeptide Y

Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. 

It is a molecule that acts as a neurotransmitter in the human body. 

It belongs to a family of peptides called neuropeptides, which are involved in various physiological processes and play a role in regulating appetite, stress response, and energy balance.

Neuropeptide Y acts as a neuromodulator and controls numerous functions in the body, including appetite regulation, energy homeostasis, stress response, cardiovascular regulation, and memory formation.

NPY is primarily known for its role in stimulating appetite and promoting food intake.

It acts on specific receptors in the hypothalamus to increase hunger and decrease satiety, leading to increased food intake.

NPY is involved in regulating energy expenditure and storage.

It promotes the storage of excess energy as fat and inhibits the breakdown of stored fat, ensuring energy availability during times of food scarcity.

NPY is released in response to stress and acts to dampen the stress response.

It produces anxiolytic (anti-anxiety) effects and regulates the body’s response to acute and chronic stressors.

NPY is present in sympathetic nerve fibers and is involved in regulating blood pressure, heart rate, and vascular tone.

It constricts blood vessels, increasing blood pressure, and promotes the growth of blood vessels.

It has been shown to play a role in memory formation and retrieval.

It acts on receptors in the hippocampus, a brain region involved in learning and memory, and influences processes related to memory consolidation and spatial memory.

NPY is primarily produced in the central nervous system, particularly in the hypothalamus.

It is also found in other parts of the body like the gastrointestinal tract. 

It acts by binding to specific receptors in the brain and peripheral tissues, influencing a variety of functions.

It is secreted alongside other neurotransmitters such as GABA and glutamate.

It is produced mainly by neurons of the sympathetic nervous system and serves as a strong vasoconstrictor and also causes growth of fat tissue.

In the brain, it is produced in various locations including the hypothalamus.

It has several functions, including: increasing food intake and storage of energy as fat, reducing anxiety and stress, reducing pain perception, affecting the circadian rhythm, reducing voluntary alcohol intake, lowering blood pressure, and controlling epileptic seizures.

NPY has been identified as being synthesized in GABAergic neurons and to act as a neurotransmitter during cellular communication. 

Neuropeptide Y is expressed in interneurons.

NPY exerts most of its effects through Neuropeptide Y receptors, mainly Y1, Y2, Y4, and Y6.

NPY is known to stimulate hunger and increase food intake by promoting the intake of carbohydrates and fats. 

It interacts with other appetite-regulating hormones and neurotransmitters to modulate hunger and satiety signals in the brain.

Additionally, NPY also plays a role in stress response and emotional regulation. 

It is released in response to stress and can affect mood, anxiety levels, and emotional states.

Plays a significant role in several physiological and psychological processes in the body.

All NPY receptors are participants in post-synaptic transmission activity, but the Y2 receptor has also been found to be involved in pre-synaptic processing.

High concentrations of neuropeptide Y synthesis and activity  are  found in the hypothalamus and hippocampus, specifically in the arcuate nucleus (ARC) and dentate gyrus. 

The arcuate nucleus has one of the highest concentrations of NPY. 

NPY regulates neuroendocrine release of various hypothalamic hormones such as luteinizing hormone.

Neuropeptide Y1 receptors have been found in highest density in the dentate gyrus.

NPY modulate the mitochondrial network by affecting the expression of many genes involved in mitochondrial functions and dynamics. 

Neuropeptide Y is involved with neurogenesis in various parts of the brain: especially the sub-ventricular zone and the dentate gyrus of the hippocampus, where cell growth and proliferation occur into adulthood.

The dentate gyrus is involved in cell proliferation modulated by various internal factors including neuropeptide Y. 

Reduction or elimination of NPY released by interneurons decreases cell growth in this brain area. 

NPY acting on Y1 receptors present on progenitor cell membranes in order to increase cell proliferation.

NPY has been found to increase cellular proliferation and differentiation in the sub-ventricular zone.

The highest levels of NPY immunoreactivity was found within the paraventricular nucleus (PVN) of the hypothalamus.

The highest cellular levels of NPY mRNA in the arcuate nucleus (ARC) of the hypothalamus.

NPYergic activity directly stimulates the release and synthesis of corticotropin hormone.

Elevating NPY-ergic activity increases food intake.

The effects of NPYergic activity on food intake is also demonstrated by the blockade of certain NPY receptors, which decreases food intake. 

It is suggested NPY is a significant predictor in weight regain after weight loss to maintain old levels of energy storage.

High levels of glucocorticosteroids causes an increase of NPY by directly activating type II glucocorticosteroids receptors and, indirectly, by abolishing the negative feedback of corticotropin-releasing factor (CRF) on NPY synthesis and release. 

Obesity-induced insulin resistance and the mutation of the leptin receptor results in the abolition of inhibition of NPYergic activity and ultimately food intake via other negative feedback mechanisms to regulate them. 

Neuropeptide Y can be used as a biosensor in early detection of childhood obesity.

NPY neurons have been shown to interact with dopaminergic reward and emotion pathways in the nucleus accumbens and amygdala, respectively. 

NPY expression levels and alcohol preference have been shown to exhibit an inverse relationship. 

NPY’s anxiolytic effects are a possible therapeutic drug target for alcoholism.

Administration of neuropeptide Y was found to reduce binge-drinking behavior.

Neuropeptide Y is an anxiolytic endogenous peptide and its levels can be modulated by stress. 

NPY is connections to the HPA axis and is necessary for stress modulation.

Higher levels of  Y receptors in the amygdala result in reduced level of anxiety.

Y receptors has been linked to anxiolytic effects in the forebrain and  pons.

Conversely, higher levels of NPY may be associated with resilience against and recovery from posttraumatic stress disorder and with dampening the fear response, allowing individuals to perform better under extreme stress.

Studies of mice and monkeys show that repeated stress—and a high-fat, high-sugar diet—stimulate the release of neuropeptide Y, causing fat to build up in the abdomen. 

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