## 2 Orexins
### Physiological Actions Mediated by Orexins  
The administration of orexin increases food intake and wakefulness, regulates locomotor activity, hormone secretion, emotional states (anxiety, panic), cognition and blood pressure and suppresses rapid eye movement sleep [15; 29] (Table 2). \begin{table}
\begin{tabular}{c c} \hline \hline
**Findings** & **References** \\ \hline Increases wakefulness and suppresses rapid eye movement sleep. Narcolepsy occurs when the _orexin 2_ _receptor_ gene is inactivated. Narcolepsy: a decrease in the level of orexin (cerebrospinal fluid) and no or a & [15; 29; 31] \\ few orexinergic neurons were observed in the hypothalamus & \\ \hline Increases food intake; regulates locomotor activity, placental development and growth hormone & \\ secretion, emotional states, cognition, body temperature, pain and blood pressure & [15; 29; 31] \\ \hline Adipose tissue: orexins A and B increased peroxisome proliferator-activated receptor-gamma-2 & [56] \\ expression; decreased expression of hormone-sensitive lipase enzyme & \\ \hline Orexin A: decreased glycerol release, promoted acid secretion, decreased the rate of gastric emptying and & \\ plasma leptin level. A fat diet and triglycerides stimulated orexin tone. Orexin A release depends on a & [14; 56; 57] \\ low glucose level & \\ \hline Lacking leptin receptors (obese animals): more widespread distribution of orexins in the central nervous & [58] \\ system than in lean animals & \\ \hline Orexins: increased motility of gastrointestinal tract, involved in glucose metabolism. Fasting: increased & \\ the level of phosphorylated cAMP response binding protein in neurons expressing orexin & [59; 60] \\ \hline Orexin A: increased plasma levels of adrenocorticproline hormone and corticosterone and mRNA levels & [29; 61; 62] \\ of steroidogenic enzyme. Action limited to a short-term due to increased wakefulness & \\ \hline Involved in the maintenance of normal insulin sensitivity with advanced age. Crucial in maintaining the & [63] \\ hypothalamic insulin signaling & \\ \hline Hyperglycemia blocked the expression of orexin. Hypoglycemic animals: higher hypothalamic level of & [60; 64] \\ orexin B than in controls & \\ \hline Orexins A and B promoted and inhibited respectively the proliferation of 3T3-L1 cells showing an & \\ adipocyte-like phenotype. Both orexins increased plasma levels of norepinephrine & [14] \\ \hline Orexins A and B: increased energy expenditure and food consumption. Fasting animals: increased & \\ hypothalamic level of prepro-orexin & & [6; 65] \\ \hline Periforical area or lateral hypothalamus: orexin A administration increased food intake. A long-term & \\ administration of orexin A did not modify daily food intake, level of glucose in blood and body weight & [29] \\ \hline Orexin A increased more the metabolic rate than orexin B. Stimulation of metabolic rate by orexin A & [65] \\ lower during the light cycle than during the dark ones & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Orexins: physiological actions and pathological conditions. Orexins are involved in endocrine (controlling the release of luteinizing hormone, and corticotropin-releasing hormone), autonomic (blood pressure, body temperature, heart rate, and breathing) and pain (decrease) actions [29]. In addition, orexin is involved in placental development and growth [15] and in the release of glucocorticoids [31]. Orexins regulate the brain reward function, and it seems that this is mediated by opioids involved in motivational mechanisms [29]. Narcolepsy occurs when the _orexin 2 receptor_ gene is inactivated; in humans, individuals suffering from narcolepsy show a decrease in the level of orexin in the cerebrospinal fluid, and no or a few orexinergic neurons are observed in the hypothalamus [29] (Table 2). In the adipose tissue, both orexins A and B increased PPAR (peroxisome proliferatorator-activated receptor)-gamma-2 expression, which is involved in adipose differentiation and decreased the expression of the hormone-sensitive lipase enzyme [56] (Table 2).