Abstract
Neurotensin (NT) is a small peptide with pleiotropic functions, exerting its primary actions by controlling food intake and energy balance. The first evidence of an involvement of NT in metabolism came from studies on the central nervous system and brain circuits, where NT acts as a neurotransmitter, producing different effects in relation to the specific region involved. Moreover, newer interesting chapters on peripheral NT and metabolism have emerged since the first studies on the NT-mediated regulation of gut lipid absorption and fat homeostasis. Intriguingly, NT enhances fat absorption from the gut lumen in the presence of food with a high fat content, and this action may explain the strong association between high circulating levels of pro-NT, the NT stable precursor, and the increased incidence of metabolic disorders, cardiovascular diseases, and cancer observed in large population studies. This review aims to provide a synthetic overview of the main regulatory effects of NT on several biological pathways, particularly those involving energy balance, and will focus on new evidence on the role of NT in controlling fat homeostasis, thus influencing the risk of unfavorable cardio–metabolic outcomes and overall mortality in humans.
Highlights
Neurotensin (NT) is a biologically active, 13 amino acid peptide derived from the intracellular proteolytic cleavage of its precursor in two fractions; the longer one is constituted of 163 amino acids and is known as proneurotensin [1]
NT exerts its biological actions by the linkage with three specific receptors named neurotensin receptor-1 (NTSR1), -2 (NTSR2), and -3 (NTSR3), the latter being known as sortilin-1 [5]
NT was shown to directly stimulate farnesoid X receptor (FXR) and bile acid transporter signaling under non-obese conditions, whereas it exerts the opposite effects in obesity, contributing to the alteration of the metabolic phenotype associated with weight excess [71]
Summary
Neurotensin (NT) is a biologically active, 13 amino acid peptide derived from the intracellular proteolytic cleavage of its precursor in two fractions; the longer one is constituted of 163 amino acids and is known as proneurotensin (pro-NT) [1]. NTSR1 is recognized as the main receptor that, among other central functions, influences energy balance [7] being expressed at both the central and peripheral level, mainly in the gastrointestinal tract [8]. In relation to the large number of brain circuits and hormone responses that NT mediates, this neuropeptide is involved in the central regulation of a broad range of biological functions, from appetite and activity behavior, to thermogenesis, nociception, blood pressure, reward mechanisms, sleep, and several others [10,11]. The overall control exerted by NT on the major metabolic pathways is integrated and accounts for central and peripheral actions, exerted through direct and indirect mechanisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
