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Ayesha Fawad, Andreas Bergmann, Joachim Struck, Peter M Nilsson, Marju Orho-Melander, Olle Melander
Context: The gut hormone neurotensin promotes fat absorption, diet-induced weight gain and liver steatosis. Its stable precursor-hormone fragment "proneurotensin" predicts cardiometabolic disease in middle-aged populations, especially in women. Objective: To test if proneurotensin predicts cardiovascular disease (CVD) and diabetes development in an elderly population and whether there are gender differences in this respect. Design, Setting and Participants: Fasting proneurotensin was measured in plasma from 4804 participants (mean age 69±6 years) of the Malmö Preventive Project (MPP) and subjects were followed up for development of CVD and diabetes during 5...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Gilda Fazzari, Merylin Zizza, Anna Di Vito, Raffaella Alò, Maria Mele, Rosalinda Bruno, Barni Tullio, Rosa Maria Facciolo, Canonaco Marcello
Recent indications are suggesting that high fat and sugar-enriched foods do not only evoke harmful physiological conditions, but they also endure evident structural alterations in cerebral regions controlling cognitive and feeding behaviors. Food consumption plus neuronal energy regulatory mechanisms seem to constitute a complex system assuring that food calories do not exceed body requirements. At the same time obesogenic-related properties of limbic feeding stations like the hypothalamus (HTH), hippocampus (HIP) and amygdala (AMY) tend to control eating habits through the interaction of distinct neuropeptides...
March 12, 2018: Behavioural Brain Research
Marc Sousbie, Élie Besserer-Offroy, Rebecca L Brouillette, Jean-Michel Longpré, Richard Leduc, Philippe Sarret, Éric Marsault
Neurotensin exerts potent analgesic effects following activation of its cognate GPCRs. In this study, we describe a systematic exploration, using structure-based design, of conformationally constraining neurotensin (8-13) with the help of macrocyclization and the resulting impacts on binding affinity, signaling, and proteolytic stability. This exploratory study led to a macrocyclic scaffold with submicromolar binding affinity, agonist activity, and greatly improved plasma stability.
March 8, 2018: ACS Medicinal Chemistry Letters
Sharma Bhavya, Pei San Lew, Tooru M Mizuno
Xenin is a gastrointestinal hormone that belongs to the neurotensin family. Central administration of xenin to obese mice reduces food intake and body weight gain and causes alterations in the expression of lipid metabolism-related genes and proteins in white adipose tissue (WAT). However, it has not been tested whether or not xenin directly acts on adipose tissue and alters lipid metabolism. The present study was performed to address this possibility by examining the effect of xenin treatment on the levels of glycerol and free fatty acids (FFA) and expression levels of lipolysis marker proteins ex vivo in cultured mouse WAT...
March 9, 2018: Biochemical and Biophysical Research Communications
Lisa Kinnavane, Seralynne D Vann, Andrew J D Nelson, Shane M O'Mara, John P Aggleton
To understand the hippocampus, it is necessary to understand the subiculum. Unlike other hippocampal subfields, the subiculum projects to almost all distal hippocampal targets, highlighting its critical importance for external networks. The present studies, in male rats and mice, reveal a new category of dorsal subiculum neurons that innervate both the mammillary bodies (MBs) and the retrosplenial cortex (RSP). These bifurcating neurons comprise almost half of the hippocampal cells that project to RSP. The termination of these numerous collateral projections was visualized within the medial mammillary nucleus and the granular RSP (area 29)...
January 2018: ENeuro
Angeliki Papapanagiotou, George Sgourakis, Stella Peristeraki, Dimitris Raptis, Kyriakos Karkoulias, Stergios Tezas, Panna Patel, Athanasios G Papavassiliou
OBJECTIVES: This pilot study aimed to determine the feasibility of serum values of osteonectin, adiponectin, transforming growth factor beta 1, and neurotensin being used in clinical practice to predict the severity of acute pancreatitis. METHODS: Blood samples were collected from 45 consecutive newly diagnosed acute pancreatitis patients and 30 matched healthy controls. The 2 groups were matched according to age, sex, weight, height, diabetes, smoking, and alcohol consumption...
April 2018: Pancreas
Manuel Lisardo Sánchez, Arturo Mangas, Luis Enrique Medina, Luis Angel Aguilar, Zaida Díaz-Cabiale, José Angel Narváez, Rafael Coveñas
INTRODUCTION: The distribution of the immunoreactive cell bodies and fibers containing neurotensin in the alpaca diencephalon was determined by an immunohistochemical technique. MATERIAL AND METHODS: The study was carried out in four male alpacas that lived at sea level. Brains of deeply anesthetized animals were fixed by perfusion with 4% paraformaldehyde. Cryostat sections were stained by a standard IHC method. RESULTS: Cell bodies containing neurotensin were observed in the zona incerta and hypothalamus...
March 8, 2018: Folia Histochemica et Cytobiologica
Hillary L Woodworth, Juliette A Brown, Hannah M Batchelor, Raluca Bugescu, Gina M Leinninger
Pharmacologic treatment with the neuropeptide neurotensin (Nts) modifies motivated behaviors such as feeding, locomotor activity, and reproduction. Dopamine (DA) neurons of the ventral tegmental area (VTA) control these behaviors, and Nts directly modulates the activity of DA neurons via Nts receptor-1. While Nts sources to the VTA have been described in starlings and rats, the endogenous sources of Nts to the VTA of mice remain incompletely understood, impeding determination of which Nts circuits orchestrate specific behaviors in this model...
February 15, 2018: Neuropeptides
Jan Korbecki, Izabela Gutowska, Ireneusz Kojder, Dariusz Jeżewski, Marta Goschorska, Agnieszka Łukomska, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka
Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the 'hallmarks of cancer' in glioblastoma multiforme...
January 23, 2018: Oncotarget
Hillary L Woodworth, Patricia A Perez-Bonilla, Bethany G Beekly, Trevor J Lewis, Gina M Leinninger
Neurotensin (Nts) promotes activation of dopamine (DA) neurons in the ventral tegmental area (VTA) via incompletely understood mechanisms. Nts can signal via the G protein-coupled Nts receptors 1 and 2 (NtsR1 and NtsR2), but the lack of methods to detect NtsR1- and NtsR2-expressing cells has limited mechanistic understanding of Nts action. To overcome this challenge, we generated dual recombinase mice that express FlpO-dependent Cre recombinase in NtsR1 or NtsR2 cells. This strategy permitted temporal control over recombination, such that we could identify NtsR1- or NtsR2-expressing cells and determine whether their distributions differed between the developing and adult brain...
January 2018: ENeuro
K László, L Péczely, A Kovács, O Zagoracz, T Ollmann, E Kertes, V Kállai, B Csetényi, Z Karádi, L Lénárd
Tridecapeptide Neurotensin (NT) is widely distributed in the central nervous system where it acts as a neurotransmitter and neuromodulator. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. Our previous data showed that NT microinjected into the CeA has positive reinforcing properties. We supposed that these effects might be due to modulations of the mesolimbic dopamine system. The aim of our study was to examine in the CeA the possible effects of NT and dopamine interaction on reinforcement by conditioned place preference test...
February 17, 2018: Behavioural Brain Research
Kenneth M McCullough, Filomene G Morrison, Jakob Hartmann, William A Carlezon, Kerry J Ressler
Molecular identification and characterization of fear controlling circuitries is a promising path towards developing targeted treatments of fear-related disorders. Three-color in situ hybridization analysis was used to determine whether somatostatin (SOM, Sst ), neurotensin (NTS, Nts ), corticotropin-releasing factor (CRF, Crf ), tachykinin 2 (TAC2, Tac2 ), protein kinase c-δ (PKC-δ, Prkcd ), and dopamine receptor 2 (DRD2, Drd2 ) mRNA colocalize in male mouse amygdala neurons. Expression and colocalization was examined across capsular (CeC), lateral (CeL), and medial (CeM) compartments of the central amygdala...
January 2018: ENeuro
I Barchetta, G Ciccarelli, F A Cimini, V Ceccarelli, M Orho-Melander, O Melander, M G Cavallo
PURPOSE: Leptin is an adipokine which regulates appetite and energy balance through a mechanism partially mediated by neurotensin (NT) in central nervous system. Besides acting as a neurotransmitter, NT is expressed in human intestine where it promotes fat absorption and its circulating levels associate with obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease. Whether a relation exists between circulating leptin and NT levels has not been investigated yet. The aim of this study was to test the hypothesis of an association between plasma leptin and NT concentration in adults with or without T2DM...
February 7, 2018: Journal of Endocrinological Investigation
Devin P Merullo, Jeremy A Spool, Changjiu Zhao, Lauren V Riters
Animals communicate in distinct social contexts to convey information specific to those contexts, such as sexual or agonistic motivation. In seasonally-breeding male songbirds, seasonal changes in day length and increases in testosterone stimulate sexually-motivated song directed at females for courtship and reproduction. Dopamine and testosterone may act in the same brain regions to stimulate sexually-motivated singing. The neuropeptide neurotensin, acting at the neurotensin receptor 1 (NTR1), can strongly influence dopamine transmission...
January 30, 2018: Journal of Chemical Neuroanatomy
Christopher W Tschumi, Michael J Beckstead
Neurotensin (NT) is a 13 amino acid neuropeptide that is expressed throughout the central nervous system and is implicated in the etiology of multiple diseases and disorders. Many primary investigations of NT-induced modulation of neuronal excitability at the level of the synapse have been conducted, but they have not been summarized in review form in nearly 30 years. Therefore, the goal of this review is to discuss the many actions of NT on neuronal excitability across brain regions as well as NT circuit architecture...
February 6, 2018: European Journal of Neuroscience
Thankan Jayasekharan, Shyam L Gupta, Vikas Dhiman
The intrinsic binding ability of seven natural peptides (oxytocin, arg8 -vasopressin, bradykinin, angiotensin-I, substance-P, somatostatin, and neurotensin) with copper in two different oxidation states (CuI/II ) derived from different Cu+/2+ precursor sources have been investigated for their charge dependent binding characteristics. The peptide-CuI/II complexes, [M - (n-1)H + nCuI ] and [M - (2n-1)H + nCuII ] are prepared/generated by the reaction of peptides with CuI solution/Cu-target and CuSO4 solution, and are analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS)...
January 15, 2018: Journal of Mass Spectrometry: JMS
Juan Pedro-Botet, David Benaiges
No abstract text is available yet for this article.
February 2018: Obesity
María E Aranda-Barradas, Maripaz Márquez, Liliana Quintanar, Jaime Santoyo-Salazar, Armando J Espadas-Álvarez, Daniel Martínez-Fong, Elizabeth García-García
Neurotensin (NTS)-polyplex is a nanoparticle system for targeted gene delivery that holds great promise for treatment of Parkinson's disease and various types of cancer. However, the high instability in aqueous suspension of NTS-polyplex nanoparticles is a major limitation for their widespread clinical use. To overcome this obstacle, we developed a clinical formulation and a lyophilization process for NTS-polyplex nanoparticles. The reconstituted samples were compared with fresh preparations by using transmission electron microscopy, dynamic light scattering, electrophoretic mobility, circular dichroism and transfection assays in vitro and in vivo...
January 3, 2018: Pharmaceutics
Laura E Schroeder, Gina M Leinninger
The peptide neurotensin (Nts) was discovered within the brain over 40 years ago and is implicated in regulating analgesia, body temperature, blood pressure, locomotor activity and feeding. Recent evidence suggests, however, that these disparate processes may be controlled via specific populations of Nts neurons and receptors. The neuronal mediators of Nts anorectic action are now beginning to be understood, and, as such, modulating specific Nts pathways might be useful in treating feeding and body weight disorders...
December 27, 2017: Biochimica et Biophysica Acta
Teresa Auguet, Gemma Aragonès, Alba Berlanga, Salomé Martínez, Fàtima Sabench, Carmen Aguilar, Beatriz Villar, Joan Josep Sirvent, Daniel Del Castillo, Cristóbal Richart
OBJECTIVE: This study was performed to investigate neurotensin plasma levels in patients with nonalcoholic fatty liver disease (NAFLD) associated with severe obesity. METHODS: The plasma levels of neurotensin in 20 women with normal weight and 51 women with morbid obesity (MO) were measured, and women were subclassified according to their hepatic histology as having MO without NAFLD (n = 18) or MO with NAFLD (n = 33). The NAFLD group included 15 women with simple steatosis (SS) and 18 women with nonalcoholic steatohepatitis (NASH)...
February 2018: Obesity
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