Neurotensin is a 13 amino acid neuropeptide present both in the central nervous system, where it is secreted by neurotensin neurons, and in the epithelial cells of the gastrointestinal tract. Its presence was discovered for the first time in the bovine hypothalamus by Leeman and Carraway3, in 1973. Numerous studies have investigated the functions of neurotensin and it has been shown that its effects are different depending on whether it is secreted at a central or peripheral level . Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay Neurotensin is involved in temperature regulation, pituitary hormone secretion1, tension regulation, and vascular permeability2. Three different neurotensin receptors (NTRs) have been discovered: NTR1, NTR2, and NTR3; these receptors recognize the C-terminal 8-13 fragment of the neuropeptide and mediate the actions of neurotensin3. The term appetite is generally used to characterize the desire for food. Eating behavior represents an important survival response and has been shown to be mainly regulated in the central nervous system2: different types of hormones are secreted and can induce an appetite-stimulating response (orexigenic hormones) or an appetite-reducing response. appetite (anorexigenic hormones). Along with this survival response, it is important to regulate energy homeostasis, to control body weight. We will then discuss the physiological role of neurotensin in appetite regulation and fat metabolism. To do this, we will first present the role of neurotensin in appetite. Next we will discuss its action on fat metabolism. Neurotensin plays a role in regulating appetite. Since its discovery, in fact, numerous studies have been carried out which have highlighted the anorexigenic role of neurotensin2. Many studies have investigated the pharmacological effects of Neurotensin and it has been shown that administration of exogenous Neurotensin reduces food intake. This important pharmacological role could reflect one of the physiological functions of neurotensin. Exogenous administration of neurotensin causes an increase in normal levels of neurotensin in the body. Therefore, an increased amount of this neuropeptide could enhance its physiological roles. However, the amount of Neurotensin injected into test subjects must be controlled, to ensure that an excessively large amount is not injected which could, potentially, disrupt the physiological roles of Neurotensin. The research of Remaury A. et al4 (5) focused on the inactivation of Neurotensin Receptor 1 (NTR1) to identify the role of the neuropeptide in the regulation of appetite. The study was conducted on mice expressing NTR1 (NTR1+/+ mice) and on NTR1 knockout mice (NTR1-/- mice). It was observed that NTR1-/- mice spontaneously consumed a greater amount of food than NTR1+/+ mice (10% increase in food consumption), resulting in a significant increase in body weight. Therefore, this indicates that the absence of NTR induces increased food consumption. Furthermore, following the administration of 10 ng of Neurotensin (in the intracerebral right lateral ventricle), a significant decrease in food consumption was observed in NTR1+/+ mice, and no changes were observed in NTR1-/- mice: Neurotensin, binding to NTR, reduced food intake. The combination of these two observations testifies to the anorexigenic role of Neurotensin, mediated by NTR1: food consumption increases in mice lacking NTR1; when exogenous Neurotensin is injected,food consumption increases in mice that express NTR1 (so neurotensin binds to the receptor) and remains unchanged in mice lacking NTR1. The role of Neurotensin in the regulation of appetite is also clarified by its importance in the action of leptin: this was studied by a study conducted by Sahu A. et al5. (6). Leptin, an anorexigenic hormone, is secreted by adipose cells and regulates fat mass in the body: the more fat present, the greater the amount of leptin secreted and the reduced appetite. The food-deprived rats were first injected with a control rabbit serum or an antiserum to neurotensin (NT-AS). They were then administered 4ug of leptin and food consumption was measured. A significant increase in food consumption was observed in rats administered leptin and NT-AS compared to the control. Thus, NT-AS reversed the anorexic action of leptin: this suggests that neurotensin may be involved in the appetite-regulating functions of leptin. To investigate this observation further, a second experiment was performed. Rats were administered leptin as well as 40 ug/kg of the neurotensin receptor (NTR) antagonist SR48692 or a control vehicle. An increase in food consumption was observed in rats administered the NTR antagonist compared to rats administered vehicle. Furthermore, rats administered SR48692 alone (without leptin) showed no change in food consumption compared to vehicle, demonstrating that the NTR antagonist alone had no influence on food consumption. The NTR antagonist therefore reversed the action of leptin on food intake. This study highlights that leptin and neurotensin work together to reduce appetite. Neurotensin appears necessary for leptin to induce its anorexigenic effect. Finally, the physiological role of neurotensin in appetite was also studied in research conducted by Ratner. C et al1 (2). This study specifically focuses on the function of neurotensin in Roux-en-Y gastric bypass (RYGB) surgery. Gastric bypass surgery is a surgical operation, carried out mainly in obese subjects, which consists in reducing the volume of the stomach, and is particularly characterized by a decrease in appetite. Relative neurotensin expression was measured in the gastrointestinal tract (using qPCR) in rats subjected to RYGB (RYGB rats) and in sham-operated rats (sham rats) (rats were given approximately 15 g of food per day) . RYBG rats weighed less than sham rats, and neurotensin gene expression was significantly higher in RYGB rats. Additionally, both cohorts of rats were administered the neurotensin antagonist SR142848A: an increase in food consumption and body weight was observed in RYBG rats compared to sham rats. These observations, therefore, support the role of Neurotensin as an appetite-regulating neuropeptide in gastric bypass surgery. Although several studies confirm the general anorexigenic effect of Neurotensin, it is important to consider the secretion of Neurotensin. Neurotensin is produced by several neurotensin neurons, located in the central nervous system. Neurotensin secreted in the Nucleus Accumbens appears not to influence appetite and eating behavior, unlike neurotensin secreted by neurons located in the ventral tegmental area or lateral hypothalamic area6. Therefore, the role of Neurotensin as an appetite-reducing neuropeptide appears to depend on the site of secretion: further research is needed to more precisely identify the Neurotensin neurons that exert a role in appetite. which one yescheck for hunger. The anorexigenic role of Neurotensin has been shown to be particularly effective in fasting-induced feeding but less evident in homeostatic feeding (food intake to regulate energy)2. Along with its role in appetite, the physiological function of Neurotensin in fat metabolism has been studied. Neurotensin has been shown to be involved in lipid absorption in the gastrointestinal tract. After exposure to a diet containing a significant amount of fat, lipid absorption was significantly lower in the absence of neurotensin. A study conducted by Li J. et al. 7 examined the function of neurotensin in lipid absorption in mice exposed to high-fat diets (60% kcal from fat). Two cohorts of mice were studied: wild-type mice (expressing neurotensin (NT), called NT+/+ mice) and NT-deficient mice (NT-/- mice). When exposed to a high-fat diet, NT-/- mice's epididymal, retroperitoneal, and pericardial fat pads were smaller than in NT+/+ mice: this resulted in lower body weight for NT- mice. /-. NT deficiency appears to reduce the amount of fat in the body. Subsequently, the action of Neurotensin on the absorption of intestinal lipids was studied. The fecal triglyceride content of NT-/- mice was 25% higher than wild-type mice, indicating a decrease in lipid absorption. To confirm this observation, mice were given SR48692, a neurotensin 1 receptor (NTR1) antagonist, and olive oil, rich in fatty acids. A decrease in fatty acid absorption was observed in NT+/+ mice. When NTR1 is blocked (by the antagonist), Neurotensin is no longer able to perform its function: lipids are absorbed less, highlighting the role of Neurotensin in fat absorption. Insulin represents another important regulator of lipid metabolism. Among other functions, it plays several roles in the synthesis of fatty acids and the breakdown of lipids. Béraud-Dufour s. et al. 8 aimed to analyze the pharmacological effect of neurotensin on insulin secretion. Isolated rat pancreatic islets and insulin-secreting beta cells were first exposed to 0.1 uM neurotensin and glucose, at two different concentrations (2 mM and 20 mM). A similar trend was observed after 45 min incubation in both populations. While neurotensin increased insulin secretion in cells exposed to 2 mM glucose, it significantly decreased insulin secretion in cells exposed to 20 µM glucose. Therefore, since neurotensin appears to regulate insulin secretion, it is involved, albeit indirectly, in lipid metabolism (through the effects of insulin). This observation, however, suggests that the action of Neurotensin on insulin is not completely understood. If glucose is administered in low doses, Neurotensin increases insulin secretion, which, therefore, promotes the synthesis of fatty acids and stimulates the accumulation of fat in adipose tissues. However, if glucose is administered in higher doses, Neurotensin has the opposite effect: it decreases insulin secretion, which translates into reduced production of fatty acids and reduced accumulation of fat in adipocytes. In conclusion, we can confirm that the physiological role of neurotensin in appetite has been widely studied: several results, most of which obtained through the study of the pharmacological role of neurotensin, suggest that this neuropeptide exerts an anorectic effect. Fewer studies have been conducted to investigate its role in fat metabolism, but neurotensin has been observed to increase., 23(1), 41-47.