what is the purpose of orexin

Orexin

• Sleep Medicine. Orexin and its cognate receptors (OX1 R and OX 2 R) play a key role in sleep/wake regulation. ...
• Sleep Hormones. ...
• Neuroendocrinology. ...
• Orexin. ...
• Narcolepsy. ...
• Orexins. ...
Orexin. ...
Orexin. ...
The Role of Neuropeptides in Addiction and Disorders of Excessive Consumption. ...
Stress and Arousal/Sleep

Full Answer

What is the function of the orexin system?

The orexin system was first suggested to be mainly involved in stimulating food intake according to the finding that the core administration of A and B caused an increase in food intake. Additionally, it modulates the visceral function, regulates the expenditure of energy and stimulates wakefulness.

What are orexins and how do they regulate motivation?

An increasing body of work has suggested that orexins (also known as hypocretins) — a pair of neuropeptides that are crucial for maintaining wakefulness — are also involved in the regulation of motivated behaviours, including feeding, emotional behaviour and reward seeking, and that these functions are mediated by two subtypes of orexin receptors.

What is the origin of the word orexin?

Orexin was discovered in 1998 almost simultaneously by two independent groups of researchers working on the rat brain. One group named it orexin, from orexis, meaning "appetite" in Greek; the other group named it hypocretin, because it is produced in the hypo thalamus and bears a weak resemblance to secretin, another peptide.

What does orexin do in the body?

Orexin neurons are “multi-tasking” neurons regulating a set of vital body functions, including sleep/wake states, feeding behavior, energy homeostasis, reward systems, cognition and mood. Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions.

What happens when orexin is released?

Central administration of orexin-A strongly promotes wakefulness, increases body temperature and locomotion, and elicits a strong increase in energy expenditure. Sleep deprivation also increases orexin-A transmission. The orexin system may thus be more important in the regulation of energy expenditure than food intake.

What is the primary action of orexin in humans?

Orexin A and B (also known as hypocretin A and B) are peptides released by neurons of the lateral hypothalamus that play an important role in mediating wakefulness and arousal.

What does a lack of orexin do?

DMH neurons signal to the orexin neurons, and lack of the orexin neurons in mice reduces the amplitude of the circadian REM sleep rhythm by about half26,79. These results suggest that the orexin neurons, along with additional projections from the DMH, help to suppress REM sleep during the active period85.

What happens when you have too much orexin?

Orexins also excite neurons important in regulating mood. Having too much or too little orexin activity has been linked to depression12 and other mental health conditions, such as anxiety, panic disorder, addictions, and post-traumatic stress disorder.

Does orexin make you hungry?

But orexin is also extremely important as a mediator of appetite. Giving orexin will increase craving for food, and giving a hormone like leptin (a signal of fullness), inhibits orexin. And this means that orexin could be a new target for problems associated with appetite, particularly things like binge eating.

What stimulates orexin production?

Eating fermented foods like sauerkraut and pickles can help increase orexin production. Fermented foods contain lactic acid, and the production of lactic acid can block glucose production, which decreases orexin production. So eating more fermented foods can actually help increase orexin production.

What stimulates orexin release?

CRH or Corticotrophin Releasing Hormone is released by the hypothalamus and activates orexin. It's released in response to stress.

How does orexin affect sleep?

Using the DREADD technique, it was reported that excitation of orexin neurons significantly increases the amount of wakefulness time, and decreases both non-REM and REM sleep times. Additionally, it was shown that inhibition of orexin neurons decreases wakefulness time and increases non-REM sleep time44).

How can I improve my orexin?

They found that amino acids -- nutrients found in proteins such as egg whites -- stimulate orexin neurons much more than other nutrients. "Sleep patterns, health, and body weight are intertwined.

How can I check my orexin level?

Orexin testing, a diagnostic procedure requiring a lumbar puncture, can detect type 1 narcolepsy in conjunction with sleep studies like multiple sleep latency tests and polysomnography.

How does orexin keep you awake?

When you're awake, those neurons send out orexins. The orexins then bind to certain orexin receptors on other neurons. When that happens, the amount of activity of those neurons goes up. In other words, these orexins encourage neuron activity so that REM sleep is blocked and you're awake and alert.

What triggers orexin release?

The orexin neurons are activated by rewards such as food or morphine (64, 68), and orexins directly excite neurons of the VTA and nucleus accumbens via OX1R and OX2R (69, 70). Orexins also make VTA neurons more excitable by increasing the expression of NMDA receptors on the cell surface for many hours (30, 31).

What causes release of orexin?

Sleep Hormones Orexin peptides are synthesized and secreted by a group of neurons mostly localized in the lateral hypothalamus including the perifornical area.

How does orexin affect sleep?

Using the DREADD technique, it was reported that excitation of orexin neurons significantly increases the amount of wakefulness time, and decreases both non-REM and REM sleep times. Additionally, it was shown that inhibition of orexin neurons decreases wakefulness time and increases non-REM sleep time44).

How does orexin promote wakefulness?

Orexin neurons promote wakefulness through monoaminergic nuclei that are wake-active. Stimulation of dopaminergic centers by orexins modulates reward systems (VTA). Peripheral metabolic signals influence orexin neuronal activity to coordinate arousal and energy homeostasis.

What is the difference between orexin and hypocretin?

Officially, hypocretin ( HCRT) is used to refer to the genes and transcripts, while orexin is used to refer to the encoded peptides. There is a high affinity between the orexin system in the rat brain and that in the human brain.

What is the orexin system?

The orexin system was initially suggested to be primarily involved in the stimulation of food intake, based on the finding that central administration of orexin-A and -B increased food intake. In addition, it stimulates wakefulness, regulates energy expenditure, and modulates visceral function.

What is the name of the neuropeptide that regulates arousal, wakefulness, and appetite?

Orexin ( / ɒˈrɛksɪn / ), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the sufferer experiences brief losses of muscle tone ( cataplexy ), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.

How many orexin neurons are there in the brain?

There are only 10,000–20,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours.

Which receptors do orexins bind to?

The orexin peptides bind to the two G-protein coupled orexin receptors, OX 1 and OX 2, with orexin-A binding to both OX 1 and OX 2 with approximately equal affinity while orexin-B binds mainly to OX 2 and is 5 times less potent at OX 1.

What are the two types of orexins?

There are two types of orexin: orexin-A and -B ( hypocretin-1 and -2). They are excitatory neuropeptides with approximately 50% sequence identity, produced by cleavage of a single precursor protein. Orexin-A is 33 amino acid residues long and has two intrachain disulfide bonds; orexin-B is a linear 28 amino acid residue peptide. Although these peptides are produced by a very small population of cells in the lateral and posterior hypothalamus, they send projections throughout the brain. The orexin peptides bind to the two G-protein coupled orexin receptors, OX 1 and OX 2, with orexin-A binding to both OX 1 and OX 2 with approximately equal affinity while orexin-B binds mainly to OX 2 and is 5 times less potent at OX 1.

Which group of neurons is closely associated with reward related functions?

Orexinergic neuron s can be differentiated into two groups based on connectivity and functionality. Orexinergic neuron s in the lateral hypothalamic group are closely associated with reward related functions, such as conditioned place preference. These neurons preferentially innervate the ventral tegmental area and the ventromedial prefrontal cortex. In contrast to the lateral hypothalamic neurons, the perifornical-dorsal group of orexinergic neurons are involved in functions related to arousal and autonomic response. These neurons project inter-hypothalamically, as well as to the brainstem, where the release of orexin modulates various autonomic processes.

What is orexin in the brain?

Orexin, also called hypocretin, is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area. Orexin exhibits its physiological effects after binding two G-protein-coupled receptors, orexin 1 receptor and orexin 2 receptor. Impairment of the orexin signal, either by deletion of the prepro-orexin or orexin 2 receptor gene or by the ablation of orexin neurons, results in a sleep disorder similar to narcolepsy, suggesting that the orexin system plays an important role in the regulation of sleep/wakefulness. In addition, previous studies have suggested that orexin is involved in energy and fluid homeostasis, emotion regulation, stress responsiveness, and reward. However, growing evidence also suggests that orexin affects the function of peripheral tissues via direct activation of orexin receptors or through activation of autonomic nervous or endocrine systems. In this review, we discuss the physiological roles of orexin not only in the central nervous system but also in the peripheral tissues.

What are orexins?

Orexins, also known as hypocretins, are orexigenic neuropeptides involved in the regulation of the sleep–wake cycle and feeding. Two hypocretins, orexin A, a 28-amino-acid peptide, and orexin B, a 33-amino-acid peptide, are synthesized in LH. The orexins bind to two orexin receptor subtypes, OX1-R in VMH and Arc and OX2-R in the PVN and hindbrain. Injection of orexin A and B into the ventricles or hypothalamus can increase food intake, but less potently than NPY. Orexins also increase drinking, food seeking, and spontaneous activity.

What is the concentration of orexin 1?

The orexin 1 receptor (OX1R, also called hypocretin receptor 1) primarily interacts with OX-A, requiring for a half-maximum response a concentration of 30 nM of OX-A but 2500 nM of OX-B ( Sakurai et al., 1998).

What is the effect of glucosensitivity on orexins?

Glucosensitivity makes orexins highly sensitive to changes in food intake. A reduction in food intake leads to increased orexin concentrations in the LH, increased orexin gene expression, and increased expression of orexin receptors. As with NPY, orexins are also sensitive to changes in leptin levels.

Where are orexin and hypocretin located?

Orexin/hypocretin neurons are localized in the perifornical area of the lateral hypothalamus and are necessary for the maintenance of waking and behavioral arousal. An absence or reduction of the orexin/hypocretin peptide or receptors results in narcolepsy with cataplexy.

Which neurons are activated by a Gaba agonist?

GABA neurons co-express orexin, and orexin neurons are activated by a GABA agonist. Orexin neurons are glucosensitive and respond to changes in blood glucose levels rapidly, making them an early hypothalamic factor for triggering food ingestion. Glucosensitivity makes orexins highly sensitive to changes in food intake.

Which receptors does orexin bind to?

Orexin specifically binds to orexin receptors OX1R and OX2R. Orexin-A binds to OX1R and OX2R with a high affinity, whereas orexin-B selectively binds to OX2R with a similar high affinity. Orexin systems have roles in regulating feeding and drinking behavior, metabolism, the sleep–wake cycle, and the endocrine system. View chapter Purchase book.

What is the name of the hormone that excites the body?

Orexin is the name given to a highly excitatory neuropeptide hormone and the two related peptides are orexin A and B.

What is the role of hypocretin in animal behavior?

The major role of hypocretin is to integrate metabolic, circadian and sleep debt influences to determine whether the animal should be asleep or awake and active.

Does sleep deprivation increase orexin?

Orexin A transmission is also increased by sleep deprivation. It is important in the regulation of energy expenditure than food intake. The craving for food is increased by orexin and it correlates with the function of the substances that promote its production.

Does orexin increase food intake?

Initially, the orexin system was suggested to be mainly involved in the stimulation of food intake, based on the finding that central administration of orexin increases food intake.

Is multiple sleep latencies shorter in patients with undetectable orexin levels than in patients with detectable?

Multiple sleep latencies are significantly shorter in patients with undetectable orexin levels than in patients with detectable orexin levels. The frequency of sleep onset REM periods is higher in patients with undetectable orexin than in patients with detectable orexin.

Have you ever purchased Orexin Tablet, Chewable?

This survey is being conducted by the WebMD marketing sciences department.

What are the ingredients in B vitamins?

B vitamins include thiamine, riboflavin, niacin / niacinamide, vitamin B6, vitamin B12, folic acid, and pantothenic acid. Some brands of B vitamins also contain ingredients such as vitamin C, vitamin E, biotin, or zinc. Consult your doctor or pharmacist if you have questions about the ingredients in your brand.

Why is a B vitamin important?

This product is a combination of B vitamins used to treat or prevent vitamin deficiency due to poor diet, certain illnesses, alcoholism, or during pregnancy. Vitamins are important building blocks of the body and help keep you in good health.

What to do if side effects persist?

If any of these effects persist or worsen, contact your doctor or pharmacist promptly. If your doctor has directed you to take this medication, remember that he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

How to use Orexin chewable?

How to use Orexin Tablet, Chewable. Take this medication by mouth, usually once daily or as directed. Follow all directions on the product package. If you have any questions, ask your doctor or pharmacist.

How much can you save on prescriptions?

Save up to 80% on your prescriptions.

Does aspartame contain alcohol?

Chewable tablets or liquid products may contain aspartame. If you have phenylketonuria (PKU) or any other condition that requires you to restrict your intake of aspartame (or phenylalanine ), consult your doctor or pharmacist about using this drug safely. Liquid forms of this product may contain sugar and/or alcohol.

What are orexins in the brain?

They were initially recognized as feed behavior regulators, but are primarily seen as key sleep/wakefulness cycle modulators. Orexins activate orexin neurons, monoaminergic and cholinergic neurons in the hypothalamus/brainstem regions to maintain a long, consolidated waking period .

What are the B vitamins?

Vitamins are important building blocks for your body and help keep you in good health. Thiamine, riboflavin, niacin/niacinamide, vitamin B6, vitamin B12, folic acid and pantothenic acid are all B vitamins. Ingredients such as vitamin C, vitamin E, biotin, and zinc are also present in certain brands of B vitamins. Consult your doctor or pharmacist if you have any questions about the ingredients in your brand.

What is the name of the neuropeptide that regulates arousal, alertness, and appetite?

Orexin , also known as hypocretin, is a neuropeptide that regulates arousal, alertness, and appetite. The most common form is narcolepsy, type 1, in which the patient experiences a short loss of muscle tone. This is caused by a lack of orexin in the brain due to the destruction of the cells that produce it.

What are the functions of orexins?

It is assumed that the primary role of orexins is to control sleep and excitement, and the neurons that release orexins are most active during the day. To keep us awake, these neuropeptides stimulate other neurons to release alert neurotransmitters such as dopamine, serotonin, and norepinephrine.

Where are orexins produced?

Orexins (also known as hypocretins) are neurotransmitters produced in small neuronal populations within the lateral (LH) and peripheral (PFA) areas of the hypothalamus. The name orexin was derived from the Greek root word for appetite, orexis.

Does orexin A increase food intake?

Crucial evidence indicates that orexin-A increases the intake of food by delaying the onset of a behaviorally normal satiety sequence. A selective orexin-1 receptor antagonist, on the other hand, suppresses food intake and advances the onset of normal satiety sequence.

Can you swallow extended release?

If you take extended-release capsules, swallow them whole. Do not crush or chew capsules or tablets with extended-release. Doing so can release all drugs at once, increasing the risk of side effects. Also, do not split the extended-release tablets unless they have a score line and your doctor or pharmacist will tell you to do so. Swallow the whole tablet or split tablet without crushing or chewing it.

What are the functions of orexin neurons?

Therefore, orexin neurons consist of the vital functional interactions with cholinergic or monoaminergic centers and hypothalamic feeding paths and provide a crucial link between the core mechanisms that are responsible for coordinating sleep and wakefulness as well as motivated behavior like looking for food and energy balance.

How does orexin affect metabolism?

Orexin or hypocretin controls sleep patterns and may affect your metabolism as well as your ability to lose weight. When your body does not produce a sufficient amount of orexin, you can consider changing your diet by consuming less carbs and sugar, for example. Doctors may recommend medication or supplements as well.

How to help low orexin levels?

If your doctor establishes that you have low orexin levels, certain medications may be prescribed to help your body boost orexin production. If orexin levels are linked to narcolepsy, your doctor may prescribe a controlled substance that you should take responsibility to avoid overdosing.

What is the function of hypocretin in narcolepsy?

The finding of hypocretin or orexin deficiency in individuals who have narcolepsy indicates that the hypothalamic neuropeptide serves a major function in the regulation and maintenance of sleep or wakeful states along with energy homeostasis. The hypothalamic neuropeptide may be particularly important for stabilizing ...

Why does lack of orexin cause narcolepsy?

For several people, lack of orexin (hypocretin) in the body causes narcolepsy. This may be the result of an autoimmune response or a genetic problem. With an autoimmune response, the body attacks parts of the body where orexin is produced. You might be able to increase orexin or hypocretin in your body.

How to increase orexin production?

Fermented foods consisting of lactic acid and producing lactic acid can inhibit glucose production, which reduces orexin production. Consuming more fermented foods can be useful for increasing orexin production.

What are the afferent and efferent systems of the orexin neurons?

The afferent and efferent systems of the orexin neurons indicate that there are interactions between the cells and sleep/wakefulness or arousal centers within the brainstem along with essential feeding centers within the hypothalamus.

What is the difference between the C-terminal and N-terminal of orexin B?

The C-terminal portion of orexin B is similar to that of orexin A , whereas the N-terminal portion is more variable . Amino-acids with blue colours in part a of the figure indicate residues that are conserved between orexin A and orexin B.

What are the cues and contexts associated with rewards?

Cues and contexts associated with rewards, including food, sex and drugs, influence the activity of orexin neurons to evoke behaviours in response to these stimuli. Orexins are essential in reward seeking: they do not influence the primary reinforcing or priming effects of rewards, but they support motivated behaviour.

How do orexin neurons promote feeding behaviour?

In summary, to promote feeding behaviour, orexin neurons are excited by food-related cues and/or a low energy balance through neuronal connections with the limbic system and by factors that indicate a low energy balance ( Fig. 2 ).

How does the orexin system regulate energy?

The orexin system might contribute to the regulation of energy homeostasis by integrating information regarding metabolic state and regulating sleep–wake state in order to support feeding behaviour 1, 16, 17. Indeed, mice lacking orexin neurons do not show an increase in wakefulness or locomotor activity in response to starvation, unlike wild-type mice 16. Moreover, prepro-orexin mRNA is upregulated in fasted animals 8, and several studies report that the firing rates of orexin neurons are influenced by glucose, triglycerides and amino acids 16, 18, 19, 20, 21. Furthermore, orexin neurons are innervated by neurons in the arcuate nucleus (which are primary sensors for plasma leptin levels) 22, and they are directly inhibited by leptin and excited by ghrelin 16. Together, these observations suggest that orexin neurons sense the metabolic and nutritional status of the animal and integrate this information to evoke the level of arousal necessary to promote food-seeking behaviour in response to negative energy balance.

How many amino acids are in orexin A?

Structural analysis of the purified peptides showed that orexin A is a 33 amino acid peptide with an amino-terminal pyroglutamyl residue, two intra-chain disulphide bonds (indicated by the red lines), and carboxy-terminal amidation.

What are orexins derived from?

8 ). Molecular cloning studies showed that orexin A and orexin B are derived from a common precursor peptide, prepro-orexin (see the figure, part a ). An mRNA encoding the same precursor peptide was independently identified by de Lecea et al. as a hypothalamus-specific transcript 132. The authors predicted that the transcript encoded a polypeptide precursor that is cleaved at amino acid residues GKR and GRR (see the figure, part a) to form two neuropeptides, hypocretin-1 and hypocretin-2 (which correspond to orexin A and orexin B, respectively). Structural analysis of the purified peptides showed that orexin A is a 33 amino acid peptide with an amino-terminal pyroglutamyl residue, two intra-chain disulphide bonds (indicated by the red lines), and carboxy-terminal amidation. This structure is completely conserved among several mammalian species (human, rat, mouse, cow, sheep, dog and pig). Orexin B is a 28 amino acid, C-terminally amidated linear peptide. Analysis of the amino acid sequence of orexin B has revealed that there are several species differences, although overall orexin B is highly conserved. The C-terminal portion of orexin B is similar to that of orexin A, whereas the N-terminal portion is more variable. Amino-acids with blue colours in part a of the figure indicate residues that are conserved between orexin A and orexin B.

What is the function of orexins?

Orexins are lateral hypothalamic neuropeptides that have a highly important role in the regulation of wakefulness. To support feeding behaviour, orexin neurons are excited by food-related cues and/or low energy balance through neuronal connections with the limbic system and through factors that indicate energy balance.

What is the function of orexin A and B?

Orexin A and orexin B are hypothalamic neuropeptides initially identified as endogenous ligands for two orphan G-protein coupled receptors (GPCRs). A deficiency of orexin signaling results in the sleep disorder narcolepsy-cataplexy in humans, dogs, and rodents, a sleep disorder characterized by excessive daytime sleepiness and cataplexy.

What is orexin A and B?

Orexin A and orexin B are hypothalamic neuropeptides initially identified as endogenous ligands for two orphan G-protein coupled receptors (GPCRs). A deficiency of orexin signaling results in the sleep disorder narcolepsy-cataplexy in humans, dogs, and rodents, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. Multiple approaches, including molecular genetic, electrophysiological, pharmacological, and neuroanatomical studies have suggested that orexins play critical roles in the maintenance of wakefulness by regulating the function of monoaminergic and cholinergic neurons that are implicated in the regulation of wakefulness. Here, I review recent advances in the understanding of how orexins regulate sleep/wakefulness and prevent narcolepsy.

How Do Orexin Antagonists Work?

Orexin antagonists are medications for treating insomnia. Orexin, also known as hypocretin, is a neurotransmitter secreted in the hypothalamus region of the brain. Neurotransmitters are substances that nerve cells (neurons) release to transmit signals to each other.

What is the function of orexin receptors?

Orexin receptors are particles on membranes of orexin neurons that initiate intracellular action to promote a state of wakefulness, when stimulated by orexin. Orexin antagonists bind to orexin receptors and block orexin from activating them, thus promoting sleep.

What is an orexin antagonist?

Orexin antagonists are oral tablets used for inducing and maintaining sleep in adults with insomnia.

Which neurons are involved in the regulation of sleep and wake states?

A cluster of orexin neurons in the hypothalamus synthesizes orexin, which is in two forms, orexin A and B. Orexin has vital functions such as regulation of sleep /wake states, energy expenditure, appetite, reward systems, mood and cognition. Orexin A and B bind to OX1 and OX2 receptors in orexin neurons to promote arousal and wakefulness.

Overview

Discovery

Isoforms

Function

Orexin neurons

Clinical uses

External links