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Brandon A Kemp, Nancy L Howell, Shetal H Padia
The intrarenal ghrelin receptor (GR) is localized to collecting duct (CD) cells where it increases αENaC-dependent sodium reabsorption in rodents. We hypothesized that chronic GR inhibition with intrarenal GR siRNA lowers blood pressure (BP) in Angiotensin II-dependent hypertension via reductions in αENaC-dependent sodium reabsorption. Uninephrectomized Sprague-Dawley rats (N=121) received subcutaneous osmotic pumps for chronic systemic delivery of Angiotensin II or vehicle (5% dextrose in water). Rats also received intrarenal infusion of vehicle, GR siRNA, or scrambled (SCR) siRNA...
June 20, 2018: American Journal of Physiology. Renal Physiology
S V Shirshev, E G Orlova, O A Loginova, I V Nekrasova, O L Gorbunova, I L Maslennikova
We studied the effect of hormones estriol, ghrelin, kisspeptin, and chorionic gonadotropin in concentrations corresponding to their content in the peripheral blood in each trimester of pregnancy on the expression of membrane molecules on myeloid and plasmacytoid dendritic cells of the thymus. It was found that thymic myeloid dendritic cells are sensitive to the action of estriol and kisspeptin. Estriol in a concentration of the first trimester of pregnancy reduces the number of myeloid dendritic cells expressing receptor for thymic stromal lymphopoietin (CD11c+TSLP-R+ ) and inhibitory molecule B7-H3 (CD11c+ CD276+ )...
June 19, 2018: Bulletin of Experimental Biology and Medicine
Lewis R Mattin, Adora M W Yau, Victoria McIver, Lewis J James, Gethin H Evans
This study investigated the acute circulating gut hormone, appetite and gastric emptying rate responses to a semi-solid meal following exercise at different intensities. Twelve men completed three trials in a randomised-crossover design, consisting of continuous cycling at 70% V˙O2Peak (HIGH), 40% V˙O2Peak (LOW) or rest (CONTROL). Baseline samples were collected after an overnight fast before undertaking the 60 min exercise or rest period, followed by 30 min rest before consumption of a standardised semi-solid meal (~242 kcal)...
June 19, 2018: Nutrients
Yi Zhang, Gang Ji, Guanya Li, Yang Hu, Li Liu, Qingchao Jin, Qianqian Meng, Jizheng Zhao, Kai Yuan, Jixn Liu, Karen M von Deneen, Antao Chen, Guangbin Cui, Huaning Wang, Qingchuan Zhao, Kaichun Wu, Jie Tian, Peter Manza, Dardo Tomasi, Nora D Volkow, Yongzhan Nie, Gene-Jack Wang
BACKGROUND/OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery to treat obesity, and involves removal of the gastric fundus where ghrelin is mainly produced. Ghrelin stimulates appetite and regulates food intake through its effect on the hypothalamus and hippocampus (HIPP). While ghrelin's role on the hypothalamus has been explored, little is known about its role on HIPP. We tested the hypothesis that LSG-induced reductions in ghrelin levels would be associated with changes in HIPP activity...
June 18, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Martina Holubova, Miroslava Blechova, Anna Kakonova, Jaroslav Kunes, Blanka Zelezna, Lenka Maletinska
Ghrelin, the only known orexigenic gut hormone produced primarily in the stomach, has lately gained attention as a potential treatment for anorexia and cachexia. However, its biological stability is highly limited, therefore a number of both peptide and non-peptide ghrelin analogs have been synthesized. In this study, we provide in vitro and in vivo characterization of a series of novel peptide growth hormone secretagogue receptor (GHS-R1a) agonists, both under non-pathological conditions and in the context of lipopolysaccharide (LPS)-induced anorexia...
June 18, 2018: Journal of Pharmacology and Experimental Therapeutics
Kouichi Yamamoto, Yukihiro Isogai, Takayuki Ishida, Keisuke Hagihara
Teriparatide is clinically used for the treatment of osteoporosis; however, nausea is often observed in patients. Its insufficient control affects the ability to continue teriparatide therapy. Rikkunshi-To (RKT), a traditional Japanese herbal medicine, improves the gastrointestinal function via activation of the ghrelin-signaling system. We investigated the therapeutic effects of RKT on teriparatide-induced nausea in rats and the involvement of ghrelin in these effects. We previously reported that ovariectomized rats showed pica (kaolin ingestion), a behavior that can be used to assess nausea in rats, after the subcutaneous administration of teriparatide; thus, the behavior was used as an index of nausea...
May 17, 2018: Journal of Pharmacological Sciences
Yu-On Jeong, Soo Jung Shin, Jun Yong Park, Bo Kyeong Ku, Ji Soo Song, Jwa-Jin Kim, Seong Gak Jeon, Sang Min Lee, Minho Moon
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and neuronal death. The primary pathogenic cause is believed to be the accumulation of pathogenic amyloid beta (Aβ) assemblies in the brain. Ghrelin, which is a peptide hormone predominantly secreted from the stomach, is an endogenous ligand for the growth hormone secretagogue-receptor type 1a (GHS-R1a). MK-0677 is a ghrelin agonist that potently stimulates the GHS-R1a ghrelin receptor...
June 18, 2018: International Journal of Molecular Sciences
Cristina Gardelli, Hiroki Wada, Asim Ray, Moya Caffrey, Antonio Llinas, Igor Shamovsky, Joakim Tholander, Joakim Larsson, Ulf Sivars, Leif Hultin, Ulf Andersson, Hitesh J Sanganee, Kristina Stenvall, Brith Leidvik, Karin Gedda, Lisa Jinton, Marie Ryden Landergren, Kostas Karabelas
Cachexia and muscle wasting are very common among patients suffering from cancer, chronic obstructive pulmonary disease and other chronic diseases. Ghrelin stimulates growth hormone secretion via the ghrelin receptor, which subsequently leads to increase of IGF-1 plasma levels. The activation of the GH/IGF-1 axis leads to an increase of muscle mass and functional capacity. Ghrelin further acts on inflammation, appetite and adipogenesis, and for this reason was considered an important target to address catabolic conditions...
June 17, 2018: Journal of Medicinal Chemistry
Wei Wang, Zhao-Xia Chen, Dong-Yu Guo, Ya-Xiong Tao
Regulation of prostate cancer by androgen and androgen receptor (AR), and blockade of AR signaling by AR antagonists and steroidogenic enzyme inhibitors have been extensively studied. G protein-coupled receptors (GPCRs) are a family of membrane receptors that regulate almost all physiological processes. Nearly 40% of FDA-approved drugs in the market target GPCRs. A variety of GPCRs that mediate reproductive function have been demonstrated to be involved in the regulation of prostate cancer. These GPCRs include gonadotropin-releasing hormone receptor, luteinizing hormone receptor, follicle-stimulating hormone receptor, relaxin receptor, ghrelin receptor, and kisspeptin receptor...
June 15, 2018: Pharmacology & Therapeutics
Chika Ikenoya, Shota Takemi, Arisa Kaminoda, Sayaka Aizawa, Shiomi Ojima, Zhi Gong, Rakhi Chacrabati, Daisuke Kondo, Reiko Wada, Toru Tanaka, Sachiko Tsuda, Takafumi Sakai, Ichiro Sakata
Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells...
June 15, 2018: Scientific Reports
Laurent Salade, Nathalie Wauthoz, Marjorie Vermeersch, Karim Amighi, Jonathan Goole
The nose-to-brain delivery of ghrelin loaded in liposomes is a promising approach for the management of cachexia. It could limit the plasmatic degradation of ghrelin and provide direct access to the brain, where ghrelin's specific receptors are located. Anionic liposomes coated with chitosan in either a liquid or a dry-powder formulation were compared. The powder formulation showed stronger adhesion to mucins (89 ± 4% vs 61 ± 4%), higher ghrelin entrapment efficiency (64 ± 2% vs 55 ± 4%), higher enzymatic protection against trypsin (26 ± 2% vs 20 ± 3%) and lower ghrelin storage degradation at 25°C (2...
June 11, 2018: European Journal of Pharmaceutics and Biopharmaceutics
W Kyle Simmons, Kaiping Burrows, Jason A Avery, Kara L Kerr, Ashlee Taylor, Jerzy Bodurka, William Potter, T Kent Teague, Wayne C Drevets
There exists little human neuroscience research to explain why some individuals lose their appetite when they become depressed, while others eat more. Answering this question may reveal much about the various pathophysiologies underlying depression. The present study combined neuroimaging, salivary cortisol, and blood markers of inflammation and metabolism collected prior to scanning. We compared the relationships between peripheral endocrine, metabolic, and immune signaling and brain activity to food cues between depressed participants experiencing increased (N = 23) or decreased (N = 31) appetite and weight in their current depressive episode and healthy control participants (N = 42)...
June 13, 2018: Molecular Psychiatry
Kyle D Flack, Kelsey Elise Ufholz, LuAnn K Johnson, John S Fitzgerald, James N Roemmich
BACKGROUND: Weight loss from exercise is often less than expected. Putative compensatory mechanisms may limit exercise-induced reductions in body fat and might be proportional to exercise energy expenditure. PURPOSE: To determine compensation (difference between accumulated exercise energy expenditure and changes in body tissue energy stores) and compensatory responses to 1500 or 3000 kcal/week of exercise energy expenditure. METHODS: Overweight to obese (n=36) sedentary men and women were randomized to groups expending 300 or 600 kcal/exercise session, 5 days/week, for 12 weeks...
June 13, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Shavawn M Forester, Adrianne M Widaman, Sridevi Krishnan, Megan G Witbracht, William F Horn, Kevin D Laugero, Nancy L Keim
Background: Multiple hormones are involved in the regulation of food intake and glucose metabolism. Past intervention studies showed a benefit of eating breakfast on satiety, but this was possibly confounded by the disruption of habitual meal patterns. Objective: The objective of this study was to compare hormonal responses, including insulin, leptin, glucagon-like peptide-1, ghrelin, peptide YY (PYY3-36), and cholecystokinin (CCK), between habitual breakfast eaters (Br-Es) and habitual skippers (Br-Ss) to a standard midday meal...
April 20, 2018: Journal of Nutrition
Ana I Duarte, Marie Sjögren, Maria S Santos, Catarina R Oliveira, Paula I Moreira, Maria Björkqvist
Neuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Combining liraglutide with the orexigenic peptide ghrelin may potentially promote brain/cognitive function in HD. The R6/2 mouse model of HD exhibits progressive central pathology, weight loss, deranged glucose metabolism, skeletal muscle atrophy and altered body composition...
June 12, 2018: Scientific Reports
Anica Klockars, Allen S Levine, Pawel K Olszewski
Hypothalamic integration of gastrointestinal and adipose tissue-derived hormones serves as a key element of neuroendocrine control of food intake. Leptin, adiponectin, oleoylethanolamide, cholecystokinin, and ghrelin, to name a few, are in a constant "cross talk" with the feeding-related brain circuits that encompass hypothalamic populations synthesizing anorexigens (melanocortins, CART, oxytocin) and orexigens (Agouti-related protein, neuropeptide Y, orexins). While this integrated neuroendocrine circuit successfully ensures that enough energy is acquired, it does not seem to be equally efficient in preventing excessive energy intake, especially in the obesogenic environment in which highly caloric and palatable food is constantly available...
June 10, 2018: Current Topics in Behavioral Neurosciences
Patrizia Lo Cascio, Concetta Calabrò, Clara Bertuccio, Carmelo Iaria, Fabio Marino, Maria G Denaro
Gastrointestinal function in vertebrates is influenced by stressors, such as fasting and refeeding, different types of diet and hormonal factors. The aim of this paper was to analyze the effect of a Spirulina ( Arthrospira platensis ) diet, a microalga known for its nutraceutical properties, on the gastrointestinal tract of zebrafish ( Danio rerio ) regarding expression of oligopeptide transporter 1 (PepT1) and ghrelin (GHR). Food deprivation and refeeding was investigated to elucidate expression of PepT1 and GHR at a gastrointestinal level and the zebrafish compensatory mechanism...
2018: Frontiers in Physiology
Catherine Chaumontet, Isidra Recio, Gilles Fromentin, Simon Benoit, Julien Piedcoq, Nicolas Darcel, Daniel Tomé
Background: Protein status is controlled by the brain, which modulates feeding behavior to prevent protein deficiency. Objective: This study tested in rats whether protein status modulates feeding behavior through brain reward pathways. Methods: Experiments were conducted in male Wistar rats (mean ± SD weight; 230 ± 16 g). In experiment 1, rats adapted for 2 wk to a low-protein (LP; 6% of energy) or a normal-protein (NP; 14% of energy) diet were offered a choice between 3 cups containing high-protein (HP; 50% of energy), NP, or LP feed; their intake was measured for 24 h...
June 1, 2018: Journal of Nutrition
David Aguinaga, Mireia Medrano, Arnau Cordomí, Mireia Jiménez-Rosés, Edgar Angelats, Mireia Casanovas, Ignacio Vega-Quiroga, Enric I Canela, Milos Petrovic, Katia Gysling, Leonardo Pardo, Rafael Franco, Gemma Navarro
Despite ancient knowledge on cocaine appetite-suppressant action, the molecular basis of such fact remains unknown. Addiction/eating disorders (e.g., binge eating, anorexia, bulimia) share a central control involving reward circuits. However, we here show that the sigma-1 receptor (σ1 R) mediates cocaine anorectic effects by interacting in neurons with growth/hormone/secretagogue (ghrelin) receptors. Cocaine increases colocalization of σ1 R and GHS-R1a at the cell surface. Moreover, in transfected HEK-293T and neuroblastoma SH-SY5Y cells, and in primary neuronal cultures, pretreatment with cocaine or a σ1 R agonist inhibited ghrelin-mediated signaling, in a similar manner as the GHS-R1a antagonist YIL-781...
June 7, 2018: Molecular Neurobiology
Kristy L Meadows
Ischemic stroke is the fifth leading cause of death in the USA and is the leading cause of serious, long-term disability worldwide. The principle sex hormones (estrogen, progesterone, and testosterone), both endogenous and exogenous, have profound effects on various stroke outcomes and have become the focus of a number of studies evaluating risk factors and treatment options for ischemic stroke. In addition, the expression of other hormones that may influence stroke outcome, including select adipose-derived hormones (adiponectin, leptin, and ghrelin), can be regulated by sex hormones and are also the focus of several ischemic stroke studies...
June 6, 2018: Hormones: International Journal of Endocrinology and Metabolism
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