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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
#1
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 13, 2017: Appetite
https://www.readbyqxmd.com/read/28228747/from-bioinactive-acth-to-acth-antagonist-the-clinical-perspective
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28190775/drp1-suppresses-leptin-and-glucose-sensing-of-pomc-neurons
#10
Anna Santoro, Michela Campolo, Chen Liu, Hiromi Sesaki, Rosaria Meli, Zhong-Wu Liu, Jung Dae Kim, Sabrina Diano
Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy and glucose metabolism. Intracellular mechanisms that enable these neurons to respond to changes in metabolic environment are ill defined. Here we show reduced expression of activated dynamin-related protein (pDRP1), a mitochondrial fission regulator, in POMC neurons of fed mice. These POMC neurons displayed increased mitochondrial size and aspect ratio compared to POMC neurons of fasted animals. Inducible deletion of DRP1 of mature POMC neurons (Drp1(fl/fl)-POMC-cre:ER(T2)) resulted in improved leptin sensitivity and glucose responsiveness...
January 30, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28186389/the-role-of-5-ht2c-receptor-on-corticosterone-mediated-food-intake
#11
Tongtong Ge, Zhuo Zhang, Jiayin Lv, Yunong Song, Jie Fan, Wei Liu, Xuefeng Wang, F Scott Hall, Bingjin Li, Ranji Cui
Corticosterone plays an important role in feeding behavior. However, its mechanism remains unclear. Therefore, the present study aimed to investigate the effect of corticosterone on feeding behavior. In this study, cumulative food intake was increased by acute corticosterone administration in a dose-dependent manner. Administration of the 5-HT2c receptor agonist m-chlorophenylpiperazin (mCPP) reversed the effect of corticosterone on food intake. The anorectic effects of mCPP were also blocked by the 5-HT2c receptor antagonist RS102221 in corticosterone-treated mice...
February 10, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28176381/the-canine-pomc-gene-obesity-in-labrador-retrievers-and-susceptibility-to-diabetes-mellitus
#12
L J Davison, A Holder, B Catchpole, C A O'Callaghan
BACKGROUND: Diabetes mellitus (DM) in dogs is a common endocrinopathy with a complex genetic architecture. Disease susceptibility in several breeds is associated with polymorphisms in immune response genes, but in the Labrador retriever breed, no genetic associations with DM have been identified. A deletion in the pro-opiomelanocortin (POMC) gene in Labrador retrievers is associated with increased appetite and risk of obesity. HYPOTHESIS/OBJECTIVES: To characterize the POMC deletion in Labrador retrievers, to develop a simple genetic test for this mutation, and to test the hypothesis that the POMC gene deletion is associated with an increased risk of DM in this breed...
February 8, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28166374/a-potential-role-for-the-secretogranin-ii-derived-peptide-em66-in-the-hypothalamic-regulation-of-feeding-behavior
#13
F Trebak, I Dubuc, A Arabo, A Alaoui, L Boukhzar, J Maucotel, M Picot, S Cherifi, C Duparc, J Leprince, G Prévost, Y Anouar, R Magoul, N Chartrel
EM66 is a conserved 66-amino acid peptide derived from secretogranin II (SgII), a member of the granin protein family. EM66 is widely distributed in secretory granules of endocrine and neuroendocrine cells as well as in hypothalamic neurons. Although EM66 is abundant in the hypothalamus, its physiological function remains to be elucidated. The aim of the present study was to investigate a possible involvement of EM66 in the hypothalamic regulation of feeding behavior. We show that ICV administration of EM66 induces a drastic dose-dependent inhibition of food intake in mice deprived of food for 18 h, which is associated with an increase of hypothalamic POMC and MC3R mRNA levels and c-Fos immunoreactivity in the POMC neurons of the arcuate nucleus...
February 6, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28166221/a-molecular-census-of-arcuate-hypothalamus-and-median-eminence-cell-types
#14
John N Campbell, Evan Z Macosko, Henning Fenselau, Tune H Pers, Anna Lyubetskaya, Danielle Tenen, Melissa Goldman, Anne M J Verstegen, Jon M Resch, Steven A McCarroll, Evan D Rosen, Bradford B Lowell, Linus T Tsai
The hypothalamic arcuate-median eminence complex (Arc-ME) controls energy balance, fertility and growth through molecularly distinct cell types, many of which remain unknown. To catalog cell types in an unbiased way, we profiled gene expression in 20,921 individual cells in and around the adult mouse Arc-ME using Drop-seq. We identify 50 transcriptionally distinct Arc-ME cell populations, including a rare tanycyte population at the Arc-ME diffusion barrier, a new leptin-sensing neuron population, multiple agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) subtypes, and an orexigenic somatostatin neuron population...
March 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28154332/a-new-pain-regulatory-system-via-the-brain-long-chain-fatty-acid-receptor-gpr40-ffa1-signal
#15
Kazuo Nakamoto
 An increasingly large number of pharmacological and physiological works on fatty acids have shown that the functional properties of fatty acids are regulated by the amount of individual fatty acid intake and the distribution of fatty acids among organs. Recently, it has been determined that G-protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA1) is activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). GPR40/FFA1 is mainly expressed in the β cell of the pancreas, spinal cord and brain...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28132887/pc1-3-deficiency-impacts-pro-opiomelanocortin-processing-in-human-embryonic-stem-cell-derived-hypothalamic-neurons
#16
Liheng Wang, Lina Sui, Sunil K Panigrahi, Kana Meece, Yurong Xin, Jinrang Kim, Jesper Gromada, Claudia A Doege, Sharon L Wardlaw, Dieter Egli, Rudolph L Leibel
We recently developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof of principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. The cognate enzyme, PC1/3, processes many prohormones in neuroendocrine and other tissues. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both short hairpin RNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28117839/the-genetic-overlap-between-mood-disorders-and-cardiometabolic-diseases-a-systematic-review-of-genome-wide-and-candidate-gene-studies
#17
REVIEW
A T Amare, K O Schubert, M Klingler-Hoffmann, S Cohen-Woods, B T Baune
Meta-analyses of genome-wide association studies (meta-GWASs) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardiometabolic diseases risk (CMD-R) genes that are also associated with mood disorders...
January 24, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28101317/corticotropin-releasing-factor-overexpression-in-mice-abrogates-sex-differences-in-body-weight-visceral-fat-and-food-intake-response-to-a-fast-and-alters-levels-of-feeding-regulatory-hormones
#18
Lixin Wang, Miriam Goebel-Stengel, Pu-Qing Yuan, Andreas Stengel, Yvette Taché
BACKGROUND: Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. METHODS: Male and female CRF-OE mice and WT littermates (4-6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28099839/trpc5-mediates-acute-leptin-and-serotonin-effects-via-pomc-neurons
#19
Yong Gao, Ting Yao, Zhuo Deng, Jong-Woo Sohn, Jia Sun, Yiru Huang, Xingxing Kong, Kai-Jiang Yu, Rui-Tao Wang, Hong Chen, Hongbo Guo, Jianqun Yan, Kathryn A Cunningham, Yongsheng Chang, Tiemin Liu, Kevin W Williams
The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28086928/resolvin-rvd2-reduces-hypothalamic-inflammation-and-rescues-mice-from-diet-induced-obesity
#20
Livia B Pascoal, Bruna Bombassaro, Albina F Ramalho, Andressa Coope, Rodrigo F Moura, Felipe Correa-da-Silva, Leticia Ignacio-Souza, Daniela Razolli, Diogo de Oliveira, Rodrigo Catharino, Licio A Velloso
BACKGROUND: Diet-induced hypothalamic inflammation is an important mechanism leading to dysfunction of neurons involved in controlling body mass. Studies have shown that polyunsaturated fats can reduce hypothalamic inflammation. Here, we evaluated the presence and function of RvD2, a resolvin produced from docosahexaenoic acid, in the hypothalamus of mice. METHODS: Male Swiss mice were fed either chow or a high-fat diet. RvD2 receptor and synthetic enzymes were evaluated by real-time PCR and immunofluorescence...
January 5, 2017: Journal of Neuroinflammation
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