The<unk>  system was initially suggested to be primarily involved in the stimulation of food intake, based on the finding that central administration of<unk> -A and -B increased food intake. In addition, it stimulates wakefulness, regulates energy expenditure, and modulates visceral function. Brown fat activation Many studies support that the<unk>  neurons regulate brown adipose tissue (BAT) activity via the sympathetic nervous system to enhance energy expenditure. Although<unk>  knockout mice were reported to show maldevelopment of brown adipose tissue (BAT), subsequent report has shown normal development of BAT. Wakefulness<unk>  seems to promote wakefulness. Recent studies indicate that a major role of the<unk>  system is to integrate metabolic, circadian and sleep debt influences to determine whether an animal should be asleep, or awake and active.<unk>  neurons strongly excite various brain nuclei with important roles in wakefulness including the dopamine, norepinephrine, histamine and acetylcholine systems and appear to play an important role in stabilizing wakefulness and sleep. The discovery that an<unk>  receptor mutation causes the sleep disorder canine narcolepsy in Doberman Pinschers subsequently indicated a major role for this system in sleep regulation. Genetic knockout mice lacking the gene for<unk>  were also reported to exhibit narcolepsy. Transitioning frequently and rapidly between sleep and wakefulness, these mice display many of the symptoms of narcolepsy. Researchers are using this animal model of narcolepsy to study the disease. Narcolepsy results in excessive daytime sleepiness, inability to consolidate wakefulness in the day (and sleep at night), and cataplexy, which is the loss of muscle tone in response to strong, usually positive, emotions. Dogs that lack a functional receptor for<unk>  have narcolepsy, while animals and people lacking the<unk>  neuropeptide itself also have narcolepsy. Central administration of<unk> -A strongly promotes wakefulness, increases body temperature and locomotion, and elicits a strong increase in energy expenditure. Sleep deprivation also increases<unk> -A transmission. The<unk>  system may thus be more important in the regulation of energy expenditure than food intake. In fact,<unk> -deficient people with narcolepsy have increased obesity rather than decreased BMI, as would be expected if<unk>  were primarily an appetite stimulating peptide. Another indication that deficits of<unk>  cause narcolepsy is that depriving monkeys of sleep for 30–36 hours and then injecting them with the neurochemical alleviates the cognitive deficiencies normally seen with such amount of sleep loss. In humans, narcolepsy is associated with a specific variant of the human leukocyte antigen (HLA) complex. Furthermore, genome-wide analysis shows that, in addition to the HLA variant, people with narcolepsy also exhibit a specific genetic mutation in the T-cell receptor alpha locus. In conjunction, these genetic anomalies cause the immune system to attack and kill the critical<unk>  neurons. Hence the absence of<unk> -producing neurons in people with narcolepsy may be the result of an autoimmune disorder. Food intake<unk>  increases the craving for food, and correlates with the function of the substances that promote its production.<unk>  is also shown to increase meal size by suppressing inhibitory postingestive feedback. However, some studies suggest that the stimulatory effects of<unk>  on feeding may be due to general arousal without necessarily increasing overall food intake. Review findings suggest that hyperglycemia that occurs in mice due to a habitual high-fat diet leads to a reduction in signalling by<unk>  receptor-2, and that<unk>  receptors may be a future therapeutic target. Leptin is a hormone produced by fat cells and acts as a long-term internal measure of energy state. Ghrelin is a short-term factor secreted by the stomach just before an expected meal, and strongly promotes food intake.<unk> -producing cells have recently been shown to be inhibited by leptin (through the leptin receptor pathway), but are activated by ghrelin and hypoglycemia (glucose inhibits<unk>  production).<unk> , as of 2007, is claimed to be a very important link between metabolism and sleep regulation. Such a relationship has been long suspected, based on the observation that long-term sleep deprivation in rodents dramatically increases food intake and energy metabolism, i.e., catabolism, with lethal consequences on a long-term basis. Sleep deprivation then leads to a lack of energy. In order to make up for this lack of energy, many people use high-carbohydrate and high-fat foods that ultimately can lead to poor health and weight gain. Other dietary nutrients, amino acids, also can activate<unk>  neurons, and they can suppress the glucose response of<unk>  neurons at physiological concentration, causing the energy balance that<unk>  maintains to be thrown off its normal cycle. Addiction Preliminary research shows potential for<unk>  blockers in the treatment of cocaine, opioid, and alcohol addiction. For example, lab rats given drugs which targeted the<unk>  system lost interest in alcohol despite being given free access in experiments. Studies of<unk>  involvement in nicotine addiction have had mixed results. For example, blocking the<unk> -1 receptor with the selective<unk>  antagonist SB-334,867 reduced nicotine self-administration in rats and that smokers who sustained damage to the insula, a brain region that regulates cravings and contains<unk> -1 receptors, lost the desire to smoke. However, other studies in rats using the dual<unk>  receptor antagonist TCS 1102 have not found similar effects. Lipid metabolism<unk> -A <unk> A) has been recently demonstrated to have a direct effect on an aspect of lipid metabolism.<unk> A stimulates glucose uptake in 3T3-L1 adipocytes and that increased energy uptake is stored as lipids (triacylglycerol).<unk> A thus increases lipogenesis. It also inhibits lipolysis and stimulates the secretion of adiponectin. These effects are thought to be mostly conferred via the PI3K pathway because this pathway inhibitor (LY294002) completely blocks<unk> A effects in adipocytes. The link between<unk> A and the lipid metabolism is new and currently under more research. Mood High levels of<unk> -A have been associated with happiness in human subjects, while low levels have been associated with sadness. The finding suggests that boosting levels of<unk> -A could elevate mood in humans, being thus a possible future treatment for disorders like depression.
Orexin
Cortisol
Thyroglobulin
Leptin
Adrenalone
Prorenin
Growth hormone
Parathyroid hormone