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https://www.readbyqxmd.com/read/28334933/disrupted-in-schizophrenia-1is-essential-for-normal-hypothalamic-pituitary-interrenal-hpi-axis-function
#1
Helen Eachus, Charlotte Bright, Vincent T Cunliffe, Marysia Placzek, Jonathan D Wood, Penelope J Watt
Psychiatric disorders arise due to an interplay of genetic and environmental factors, including stress. Studies in rodents have shown that mutants for Disrupted-In-Schizophrenia-1 (DISC1), a well-accepted genetic risk factor for mental illness, display abnormal behaviours in response to stress, but the mechanisms through which DISC1 affects stress responses remain poorly understood. Using two lines of zebrafish homozygous mutant for disc1, we investigated behaviour and functioning of the hypothalamic-pituitary-interrenal (HPI) axis, the fish equivalent of the hypothalamic-pituitary-adrenal (HPA) axis...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28323920/perinatal-exposure-to-low-dose-bisphenol-a-bpa-disrupts-the-structural-and-functional-development-of-the-hypothalamic-feeding-circuitry
#2
Harry MacKay, Zachary R Patterson, Alfonso Abizaid
Bisphenol-A (BPA) is a component of polycarbonate and other plastics to which humans are regularly exposed at low levels. BPA is characterized as an endocrine disruptor due to observations of its estrogenic activity in various experimental models. We have previously shown evidence of disrupted hypothalamic feeding circuitry and leptin sensitivity in adult BPA-exposed animals subject to a high-fat diet, but because these animals were already exhibiting a diet-induced obese phenotype, we could not rule out the possibility that these observations were simply consequences of the obesity, not a pre-existing phenotype produced by BPA exposure...
February 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323039/pomc-and-npy-mrna-expression-during-development-is-increased-in-rat-offspring-brain-from-mothers-fed-with-a-high-fat-diet
#3
Marianne Orlandini Klein, Harry MacKay, Alexander Edwards, Su-Bin Park, Ana Carolina Inhasz Kiss, Luciano Freitas Felicio, Alfonso Abizaid
Developmental programming is influenced by perinatal nutrition and it has long-lasting impacts on adult metabolism in the offspring. In particular, maternal high fat diet has been associated with increased risk of obesity and metabolic disorders during adulthood in the descendants. These effects may be due to the effects of the high fat diet on the development of the systems that regulate food intake and energy balance in the offspring hypothalamus. The arcuate nucleus (ARC) may be a particularly sensitive region to it as this nucleus contains the POMC and AgRP/NPY neurons that integrate the melanocortin system...
March 18, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28301916/a-role-of-central-nell2-in-the-regulation-of-feeding-behavior-in-rats
#4
Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee
A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored...
March 15, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28292966/endothelial-hif-1%C3%AE-enables-hypothalamic-glucose-uptake-to-drive-pomc-neurons
#5
Luis Varela, Shigetomo Suyama, Yan Huang, Marya Shanabrough, Matthias H Tschoep, Xiao-Bing Gao, Frank J Giordano, Tamas L Horvath
Glucose is the primary driver of hypothalamic POMC neurons. Here, we show that endothelial HIF-1α controls glucose uptake in the hypothalamus, and, that it is up-regulated in conditions of under-nourishment during which POMC neuronal activity is decreased. Endothelium-specific knockdown of HIF-1α impairs the ability of POMC neurons to adapt to the changing metabolic environment in vivo resulting in overeating of mice after food deprivation. The impaired functioning of POMC neurons was reversed ex vivo or by parenchymal glucose administration...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28283578/molecular-identification-and-functional-analysis-of-ctrp9-in-epinephelus-coioides
#6
Guokun Yang, Chaobin Qin, Bin Wang, Jirong Jia, Xi Yuan, Caiyun Sun, Wensheng Li
CTRP9 is a member of the C1q/TNF-related protein (CTRP) superfamily and has been studied in mammals, while the comparative studies of CTRP9 in non-mammalian species are still absent. In this study, CTRP9 was isolated and characterized from the orange-spotted grouper (Epinephelus coioides). The full length cDNA of CTRP9 was 1378 bp in size with ORF (open reading frame) of 1020 bp which encods a 339 amino acids preprohormone. The mRNA expression of CTRP9 showed a rather high level in the kidney and brain, but low level in other tissues...
March 10, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28275132/impact-of-polyunsaturated-and-saturated-fat-overfeeding-on-the-dna-methylation-pattern-in-human-adipose-tissue-a-randomized-controlled-trial
#7
Alexander Perfilyev, Ingrid Dahlman, Linn Gillberg, Fredrik Rosqvist, David Iggman, Petr Volkov, Emma Nilsson, Ulf Risérus, Charlotte Ling
Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) have different metabolic responses.Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial.Design: We studied the effects of 7 wk of excessive SFA (n = 17) or PUFA (n = 14) intake (+750 kcal/d) on the DNA methylation of ∼450,000 sites in human subcutaneous adipose tissue...
March 8, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28274841/role-of-the-brain-melanocortins-in-blood-pressure-regulation
#8
Jussara M do Carmo, Alexandre A da Silva, Zhen Wang, Taolin Fang, Nicola Aberdein, Cecilia E Perez de Lara, John E Hall
Melanocortins play an important role in regulating blood pressure (BP) and sympathetic nervous system (SNS) activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals. In experimental models of hypertension with high SNS activity, blockade of the melanocortin-4 receptor (MC4R) reduces BP despite causing marked hyperphagia and obesity. Activation of the central nervous system (CNS) pro-opiomelanocortin (POMC)-MC4R pathway appears to be an important link between obesity, SNS activation and hypertension...
March 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28271037/cholinergic-neurons-in-the-dorsomedial-hypothalamus-regulate-food-intake
#9
Jae Hoon Jeong, Dong Kun Lee, Young-Hwan Jo
OBJECTIVE: Central cholinergic neural circuits play a role in the regulation of feeding behavior. The dorsomedial hypothalamus (DMH) is considered the appetite-stimulating center and contains cholinergic neurons. Here, we study the role of DMH cholinergic neurons in the control of food intake. METHODS: To selectively stimulate DMH cholinergic neurons, we expressed stimulatory designer receptors exclusively activated by designer drugs (DREADDs) and channelrhodopsins in DMH cholinergic neurons by injection of adeno-associated virus (AAV) vectors into the DMH of choline acetyltransferase (ChAT)-IRES-Cre mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28242329/the-effects-of-intracerebroventricular-infusion-of-irisin-on-feeding-behaviour-in-rats
#10
Suat Tekin, Yavuz Erden, Fatma Ozyalin, Yilmaz Cigremis, Cemil Colak, Suleyman Sandal
Irisin, a novel exercise-induced myokine, has attracted attention with its effects on energy metabolism. This study was conducted to determine the possible effects of irisin on nutritional behaviour. In this study, 40 male Wistar Albino rats were separated into 4 groups (n=10 for each group). Osmotic mini-pumps were connected to metal cannulas implanted to lateral ventricle; and artificial cerebrospinal fluid (vehicle), and 10 and 100nM of irisin was infused for 7days. The daily food and water consumptions and body weights of rats were followed up...
February 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28235700/confirmation-that-a-deletion-in-the-pomc-gene-is-associated-with-body-weight-of-labrador-retriever-dogs
#11
M Mankowska, P Krzeminska, M Graczyk, M Switonski
A 14-bp deletion present in the proopiomelanocortin (POMC) gene of Labrador and Flat Coat Retrievers (FCR), but absent in POMC of other breeds, disrupts the β-MSH and β-endorphin coding sequences. This deletion was recently reported as strongly associated with increased body weight and obesity. We searched for this mutation in a cohort of 272 dogs, representing four breeds with a known predisposition to obesity (Labrador and Golden Retrievers, Beagle, and Cocker Spaniel) and, as expected, we found it only in Labradors...
February 16, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28229938/participation-of-ghrelin-signalling-in-the-reciprocal-regulation-of-hypothalamic-npy-pomc-mediated-appetite-control-in-amphetamine-treated-rats
#12
Ching-Han Yu, Shu-Chen Chu, Pei-Ni Chen, Yih-Shou Hsieh, Dong-Yih Kuo
Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) have been documented to participate in amphetamine (AMPH)-induced appetite suppression. This study investigated whether ghrelin signalling is associated with changes in NPY/POMC-mediated appetite control. Rats were given AMPH daily for four days, and changes in food intake, body weight, plasma ghrelin, hypothalamic NPY, melanocortin 3 receptor (MC3R), ghrelin O-acyltransferase (GOAT), acyl ghrelin (AG) and ghrelin receptor (GHSR1a) were examined and compared...
February 14, 2017: Appetite
https://www.readbyqxmd.com/read/28228747/from-bioinactive-acth-to-acth-antagonist-the-clinical-perspective
#13
REVIEW
Chiraz Ghaddhab, Jean-Marc Vuissoz, Johnny Deladoëy
The adrenocorticotropic hormone (ACTH) is a pituitary hormone derived from a larger peptide, the proopiomelanocortin (POMC), as are the MSHs (α-MSH, β-MSH, and γ-MSH) and the β-LPH-related polypeptides (Figure 1A). ACTH drives adrenal steroidogenesis and growth of the adrenal gland. ACTH is a 39 amino acid polypeptide that binds and activates its cognate receptor [melanocortin receptor 2 (MC2R)] through the two regions H6F7R8W9 and K15K16R17R18P19. Most POMC-derived polypeptides contain the H6F7R8W9 sequence that is conserved through evolution...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28214331/pomc-maintains-tumor-initiating-properties-of-tumor-tissue-derived-long-term-cultured-breast-cancer-stem-cells
#14
Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P Zhou, Mien-Chie Hung, Xiaoming Xie
The identification and understanding of the molecular network of cancer stem cells (CSCs) have had a profound impact on our view of carcinogenesis and treatment strategy. Unfortunately, a major problem is that serial passages of CSCs from clinical solid tumor specimens currently are not available in any lab, and thus, reported data are difficult to confirm and intensively interrogated. Here, we have generated two tumor tissue-derived breast CSC (BCSC) lines that showed prolonged maintenance over 20 serial passages in vitro, while retaining their tumor-initiating biological properties...
February 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28213613/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-fat-mass-via-affecting-energy-expenditure
#15
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Shanghai Chen, Feifan Guo
Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. Here, we showed that hypothalamic pro-opiomelanocortin (POMC) neurons specific ATF4 knockout (PAKO) mice are lean and have higher energy expenditure. Furthermore, PAKO mice were resistant to high-fat diet (HFD)-induced obesity, glucose intolerance and leptin resistance. Moreover, the expression of autophagy protein 5 (ATG5) was increased or decreased by ATF4 knockdown or over-expression, respectively, and ATF4 inhibited the transcription of ATG5 by binding to the basic zipper-containing protein (bZIP) sites on its promoter...
February 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28210900/false-responses-of-renilla-luciferase-reporter-control-to-nuclear-receptor-tr4
#16
Dongyun Zhang, Sam S Atlasi, Krishna K Patel, Zihao Zhuang, Anthony P Heaney
Renilla luciferase reporter is a widely used internal control in dual luciferase reporter assay system, where its transcription is driven by a constitutively active promoter. However, the authenticity of the Renilla luciferase response in some experimental settings has recently been questioned. Testicular receptor 4 (TR4, also known as NR2C2) belongs to the subfamily 2 of nuclear receptors. TR4 binds to a direct repeat regulatory element in the promoter of a variety of target genes and plays a key role in tumorigenesis, lipoprotein regulation, and central nervous system development...
February 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28202578/p38%C3%AE-mapk-signaling-mediates-exenatide-stimulated-microglial-%C3%AE-endorphin-expression
#17
Hai-Yun Wu, Xiao-Fang Mao, Hui Fan, Yong-Xiang Wang
Upon recent discovery, it has been established that activation of glucagon-like peptide-1 receptors (GLP-1Rs) exhibits neuroprotection and antinociception through microglial β-endorphin expression. This study aims to explore its underlying signaling mechanisms. GLP-1Rs and β-endorphin were co-expressed in primary cultures of microglia. Treatment with the GLP-1R agonist exenatide concentration-dependently stimulated microglial expression of the β-endorphin precursor gene POMC and peptide, with EC50 values of 4...
February 15, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28192820/estrogen-maintains-skeletal-muscle-in-septic-rats-associated-with-altering-hypothalamic-inflammation-and-neuropeptides
#18
Chenyan Zhao, Jun Li, Minhua Cheng, Jialing Shi, Juanhong Shen, Tao Gao, Fengchan Xi, Wenkui Yu
Muscle wasting is one of the main contributors to the worse outcomes in sepsis. Whether estrogen could alleviate muscle wasting induced by sepsis remains unclear. This study was designed to test the effect of estrogen on muscle wasting and its relationship with central alteration in sepsis. Thirty Sprague-Dawley rats were divided into 3 groups: control group, sepsis group, and estrogen treated sepsis group. Animals were intraperitoneally injected with lipopolysaccharide (10 mg/kg) or saline, followed by subcutaneous injection of 17β-estradiol (1 mg/kg) or saline...
February 13, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28192062/pomc-neurons-from-birth-to-death
#19
Chitoku Toda, Anna Santoro, Jung Dae Kim, Sabrina Diano
The hypothalamus is an evolutionarily conserved brain structure that regulates an organism's basic functions, such as homeostasis and reproduction. Several hypothalamic nuclei and neuronal circuits have been the focus of many studies seeking to understand their role in regulating these basic functions. Within the hypothalamic neuronal populations, the arcuate melanocortin system plays a major role in controlling homeostatic functions. The arcuate pro-opiomelanocortin (POMC) neurons in particular have been shown to be critical regulators of metabolism and reproduction because of their projections to several brain areas both in and outside of the hypothalamus, such as autonomic regions of the brain stem and spinal cord...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28191524/renin-angiotensin-aldosterone-system-in-insulin-resistance-and-metabolic-syndrome
#20
Undurti N Das
Obesity and its consequent complications such as hypertension and metabolic syndrome are increasing in incidence in almost all countries. Insulin resistance is common in obesity. Renin- angiotensin system (RAS) is an important target in the treatment of hypertension and drugs that act on RAS improve insulin resistance and decrease the incidence of type 2 diabetes mellitus, explaining the close association between hypertension and type 2 diabetes mellitus. RAS influences food intake by modulating the hypothalamic expression of neuropeptide Y and orexins via AMPK dephosphorylation...
June 1, 2016: Journal of Translational Internal Medicine
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