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https://www.readbyqxmd.com/read/29147564/a-review-of-orexin-s-unprecedented-potential-as-a-novel-highly-specific-treatment-for-various-localized-and-metastatic-cancers
#1
REVIEW
Nicole L Graybill, Volkmar Weissig
A systematic review was conducted to categorize the types of cancerous tissues that express orexin receptors and also to examine the effect of in vitro administration of orexin A or B to corresponding cell samples. Comprehensive literature analyses of primary experimental studies were performed. The results of the review included an increased frequency of orexin receptor expression in many colon and prostate cancer tissues and an upward trend of pro-apoptotic activity in these aggressive cell types.
2017: SAGE Open Medicine
https://www.readbyqxmd.com/read/29145540/inverse-association-of-peripheral-orexin-a-with-insulin-resistance-in-type-2-diabetes-mellitus-a-randomized-clinical-trial
#2
Mitra Zarifkar, Sina Noshad, Mona Shahriari, Mohsen Afarideh, Elias Khajeh, Zahra Karimi, Alireza Ghajar, Alireza Esteghamati
AIMS: To investigate the association between serum orexin concentrations and insulin resistance/sensitivity in a sample of patients with type 2 diabetes mellitus, and to study the effects of anti-hyperglycemic treatment on orexin concentrations over three months. METHODS: This study was designed as a randomized, open-label, clinical trial. Before allocation, sixty medication-naïve, newly-diagnosed, type 2 diabetes patients underwent a 75 g oral glucose tolerance test (OGTT)...
July 2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/29145494/global-analysis-of-gene-expression-mediated-by-ox1-orexin-receptor-signaling-in-a-hypothalamic-cell-line
#3
Eric Koesema, Thomas Kodadek
The orexins and their cognate G-protein coupled receptors have been widely studied due to their associations with various behaviors and cellular processes. However, the detailed downstream signaling cascades that mediate these effects are not completely understood. We report the generation of a neuronal model cell line that stably expresses the OX1 orexin receptor (OX1) and an RNA-Seq analysis of changes in gene expression seen upon receptor activation. Upon treatment with orexin, several families of related transcription factors are transcriptionally regulated, including the early growth response genes (Egr), the Kruppel-like factors (Klf), and the Nr4a subgroup of nuclear hormone receptors...
2017: PloS One
https://www.readbyqxmd.com/read/29143330/short-term-high-fat-diet-primes-excitatory-synapses-for-long-term-depression-in-orexin-neurons
#4
Victoria Linehan, Lisa Fang, Michiru Hirasawa
Overconsumption of high-fat diets is one of the strongest contributing factors to the rise of obesity rates. Orexin neurons are known to be activated by palatable high-fat diet and mediate the activation of the mesolimbic reward pathway, resulting in further food intake. While short-term exposure to high-fat diet is known to induce synaptic plasticity within the mesolimbic pathway, it is unknown if such changes occur in orexin neurons. To investigate this, 3-week old male rats were fed a palatable high-fat western diet (WD) or control chow for 1 week and then in vitro patch clamp recording was performed...
November 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29138106/the-subthalamic-neurons-are-activated-by-both-orexin-a-and-orexin-b
#5
Qing Sheng, Yan Xue, Ying Wang, An-Qi Chen, Cui Liu, Yun-Hai Liu, Hong-Yan Chu, Lei Chen
The subthalamic nucleus is an important nucleus in the indirect pathway of the basal ganglia circuit and therefore is involved in motor control under both normal and pathological conditions. Morphological studies reveal that the subthalamic nucleus receives relatively dense orexinergic projections originating from the hypothalamus. Both orexin-1 (OX1) and orexin-2 (OX2) receptors are expressed in the subthalamic nucleus. To explore the functions of orexinergic system in the subthalamic nucleus, extracellular electrophysiological recordings and behavioral tests were performed in the present study...
November 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/29137471/serum-levels-of-spexin-and-kisspeptin-negatively-correlate-with-obesity-and-insulin-resistance-in-women
#6
P A Kołodziejskii, E Pruszyńska-Oszmałek, E Korek, M Sassek, D Szczepankiewicz, P Kaczmarek, L Nogowski, P Maćkowiak, K W Nowak, H Krauss, M Z Strowski
Spexin (SPX) and kisspeptin (KISS) are novel peptides relevant in the context of regulation of metabolism, food intake, puberty and reproduction. Here, we studied changes of serum SPX and KISS levels in female non-obese volunteers (BMI<25 kg/m2) and obese patients (BMI>35 kg/m2). Correlations between SPX or KISS with BMI, McAuley index, QUICKI, HOMA IR, serum levels of insulin, glucagon, leptin, adiponectin, orexin-A, obestatin, ghrelin and GLP-1 were assessed. Obese patients had lower SPX and KISS levels as compared to non-obese volunteers (SPX: 4...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29129795/orexin-a-hypocretin-1-immunoreactivity-in-the-lateral-hypothalamus-is-reduced-in-genetically-obese-but-not-in-diet-induced-obese-mice
#7
J Antonio González, Jochen H M Prehn
The mechanisms that link diet and body weight are not fully understood. A diet high in fat often leads to obesity, and this in part is the consequence of diet-induced injury to specific hypothalamic nuclei. It has been suggested that a diet high in fat leads to cell loss in the lateral hypothalamus, which contains specific populations of neurones that are essential for regulating energy homoeostasis; however, we do not know which cell types are affected by the diet. We studied the possibility that high-fat diet leads to a reduction in orexin-A/hypocretin-1 (Hcrt1) and/or melanin-concentrating hormone (MCH) immunoreactivity in the lateral hypothalamus...
November 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/29129052/synthesis-and-evaluation-of-orexin-1-receptor-antagonists-with-improved-solubility-and-cns-permeability
#8
David A Perrey, Ann M Decker, Yanan Zhang
Orexins are hypothalamic neuropeptides playing important roles in many functions including the motivation of addictive behaviors. Blockade of the orexin-1 receptor has been suggested as a potential strategy for the treatment of drug addiction. We have previously reported OX1 receptor antagonists based on the tetrahydroisoquinoline scaffold with excellent OX1 potency and selectivity; however, these compounds had high lipophilicity (clogP > 5) and low to moderate solubility. In an effort to improve their properties, we have designed and synthesized a series of analogs where the 7-position substituents known to favor OX1 potency and selectivity were retained, and groups of different nature were introduced at the 1-position where substitution was generally tolerated as demonstrated in previous studies...
November 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29107703/orexin-hypocretin-treatment-restores-hippocampal-dependent-memory-in-orexin-deficient-mice
#9
Vijayakumar Mavanji, Tammy A Butterick, Cayla M Duffy, Joshua P Nixon, Charles J Billington, Catherine M Kotz
Orexin A is produced in neurons of the lateral, perifornical and dorsomedial regions of the lateral hypothalamic area, which then project widely throughout the central nervous system to regulate arousal state, sleep-wake architecture, energy homeostasis and cognitive processes. Disruption of orexin signaling leads to sleep disturbances and increased body mass index, but recent studies also indicate that orexin neuron activation improves learning and memory. We hypothesized that hippocampal orexin receptor activation improves memory...
October 28, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29107089/orexins-hypocretins-and-sex
#10
EDITORIAL
Olaf Jöhren
No abstract text is available yet for this article.
October 26, 2017: Peptides
https://www.readbyqxmd.com/read/29104046/cardiovascular-pressor-effects-of-orexins-in-the-dorsomedial-hypothalamus
#11
Tzu-Ling Li, Jennifer Y S Chen, Shang-Cheng Huang, Yu-Wen E Dai, Ling-Ling Hwang
Orexins are important regulators of cardiovascular functions in various physiological and pathological conditions. The dorsomedial hypothalamus (DMH), an essential mediator of cardiovascular responses to stress, contains dense orexinergic innervations and receptors. We examined whether orexins can regulate cardiovascular functions through their actions in the DMH in anesthetized rats. An intra-DMH injection of orexin A (30pmol) produced elevation of arterial pressure and heart rate. Orexin A-sensitive sites were located within or immediately adjacent to the DMH and larger responses were induced at the compact part of the dorsomedial hypothalamic nucleus...
November 2, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29102876/maternal-high-fat-diet-induces-sex-specific-endocannabinoid-system-changes-in-newborn-rats-and-programs-adiposity-energy-expenditure-and-food-preference-in-adulthood
#12
Camilla P Dias-Rocha, Mariana M Almeida, Erika M Santana, Julia C B Costa, Juliana G Franco, Carmen C Pazos-Moura, Isis H Trevenzoli
Early life inadequate nutrition triggers developmental adaptations and adult chronic disease. Maternal high-fat (HF) diet promotes visceral obesity and hypothalamic leptin resistance in male rat offspring at weaning and adulthood. Obesity is related to over active endocannabinoid system (ECS). The ECS consists mainly of endogenous ligands, cannabinoid receptors (CB1 and CB2), and the enzymes fatty acid anandamide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). We hypothesized that perinatal maternal HF diet would regulate offspring ECS in hypothalamus and brown adipose tissue (BAT) at birth, prior to visceral obesity development, and program food preference and energy expenditure of adult offspring...
October 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29096748/organic-chromium-modifies-the-expression-of-orexin-and-glucose-transporters-of-ovarian-in-heat-stressed-laying-hens
#13
O Ozdemir, M Tuzcu, N Sahin, C Orhan, Z Tuzcu, K Sahin
In this study, the effect of the supplemental organic chromium (Cr) forms on the expression of ovarian orexin(hypocretin), glucose transporters (GLUTs), heat shock proteins (HSPs) andnuclear factor-kappaB (NF-κB)were investigated in laying hens (HS). Laying hens (n=1800; 16-wk-old; Lohmann LSL-Lite) were allocated to 6 random groups according to a 2 × 3 factorial trial scheme with two different environmental temperatures [Thermoneutral (TN groups; at either 22±2 °C 24 h/d)  and heat stress (HS groups; at 34±2 °C for 8 h/d, 08:00 to 17:00 h, followed by 22°C for 16 h for a period of 12 wks)], andhens reared under both environmental conditions were fed either a basal diet or the basal diet supplemented with 1...
October 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29089444/pre-synaptic-regulation-of-leptin-in-a-defined-lateral-hypothalamus-ventral-tegmental-area-neurocircuitry-depends-on-energy-state
#14
Jing-Jing Liu, Nicholas T Bello, Zhiping P Pang
Synaptic transmission controls information flow in the brain and expression of all brain-related behaviors, including food intake. Leptin, an adipocyte-derived hormone, acts on neurons located in the lateral hypothalamus (LHA) to maintain energy homeostasis and regulate food intake behavior. The specific synaptic mechanisms, cell types and neural projections mediating this effect remain unclear. In male mice, using pathway-specific retrograde tracing, whole cell patch clamp recordings and posthoc cell type identification, we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone (MCH) and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine signaling and motivation for feeding...
October 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29073109/opioid-and-orexin-hedonic-hotspots-in-rat-orbitofrontal-cortex-and-insula
#15
Daniel C Castro, Kent C Berridge
Hedonic hotspots are brain sites where particular neurochemical stimulations causally amplify the hedonic impact of sensory rewards, such as "liking" for sweetness. Here, we report the mapping of two hedonic hotspots in cortex, where mu opioid or orexin stimulations enhance the hedonic impact of sucrose taste. One hedonic hotspot was found in anterior orbitofrontal cortex (OFC), and another was found in posterior insula. A suppressive hedonic coldspot was also found in the form of an intervening strip stretching from the posterior OFC through the anterior and middle insula, bracketed by the two cortical hotspots...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29066557/neuromedin-b-expression-defines-the-mouse-retrotrapezoid-nucleus
#16
Yingtang Shi, Ruth L Stornetta, Daniel S Stornetta, Suna Onengut-Gumuscu, Emily A Farber, Stephen D Turner, Patrice G Guyenet, Douglas A Bayliss
The retrotrapezoid nucleus (RTN) consists, by definition, of Phox2b-expressing, glutamatergic, non-catecholaminergic, non-cholinergic neurons located in the parafacial region of the medulla oblongata. An unknown proportion of RTN neurons are central respiratory chemoreceptors and there is mounting evidence for biochemical diversity among these cells. Here, we used multiplexed in situ hybridization and single-cell RNA-Seq in male and female mice to provide a more comprehensive view of the phenotypic diversity of RTN neurons...
October 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29065953/lemborexant-a-dual-orexin-receptor-antagonist-dora-for-the-treatment-of-insomnia-disorder-results-from-a-bayesian-adaptive-randomized-double-blind-placebo-controlled-study
#17
Patricia Murphy, Margaret Moline, David Mayleben, Russell Rosenberg, Gary Zammit, Kate Pinner, Shobha Dhadda, Quan Hong, Luigi Giorgi, Andrew Satlin
STUDY OBJECTIVES: To identify dose(s) of lemborexant that maximize insomnia treatment efficacy while minimizing next-morning residual sleepiness and evaluate lemborexant effects on polysomnography (PSG) measures (sleep efficiency [SE], latency to persistent sleep [LPS], and wake after sleep onset [WASO]) at the beginning and end of treatment. METHODS: Adults and elderly subjects with insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition were enrolled in a multicenter, randomized, double-blind, placebo-controlled, Bayesian, adaptive, parallel-group study, receiving lemborexant (1, 2...
October 18, 2017: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/29056152/orexin-hypocretin-system-role-in-food-and-drug-overconsumption
#18
Jessica R Barson, Sarah F Leibowitz
The neuropeptide orexin/hypocretin (OX), while largely transcribed within the hypothalamus, is released throughout the brain to affect complex behaviors. Primarily through the hypothalamus itself, OX homeostatically regulates adaptive behaviors needed for survival, including food intake, sleep-wake regulation, mating, and maternal behavior. However, through extrahypothalamic limbic brain regions, OX promotes seeking and intake of rewarding substances of abuse, like palatable food, alcohol, nicotine, and cocaine...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29054286/functional-roles-of-orexin-hypocretin-receptors-in-reward-circuit
#19
Abbas Haghparast, Zahra Fatahi, Reza Arezoomandan, Sara Karimi, Zahra Taslimi, Shahram Zarrabian
Since its first discovery in 1998, it has become clear that the orexinergic system plays an important role in regulating a number of functions including food, sex, social connections, and most prominently reward-related behaviors. Orexinergic neurons in the lateral hypothalamus project extensively to other brain areas, two most important of which are the ventral tegmental area and the nucleus accumbens that are involved in reward processing. In this review, we have presented the work in our laboratory along with the work of others and have discussed the possible functions we can infer from the research...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/29053993/orexin-system-in-swine-ovarian-follicles
#20
R Ciccimarra, S Bussolati, F Grasselli, S Grolli, L Ragionieri, F Ravanetti, M Botti, F Gazza, A Cacchioli, R Di Lecce, A M Cantoni, G Basini
Successful reproduction is strictly linked to metabolic cues. The orexins are a family of hypothalamic neurohormones, well known for their key role in the control of food intake and the involvement in several aspects of the reproductive process. The biological actions of both orexins are carried out through binding to the related Orexin 1 (OX1R) and Orexin 2 (OX2R) G-protein-coupled receptors. The purpose of this study was to investigate the presence of orexin system components in the porcine ovaries, to contribute to expand the knowledge about their pleiotropic role...
September 22, 2017: Domestic Animal Endocrinology
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