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Pro-opiomelanocortin

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https://www.readbyqxmd.com/read/28214331/pomc-maintains-tumor-initiating-properties-of-tumor-tissue-derived-long-term-cultured-breast-cancer-stem-cells
#1
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
#2
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/28192062/pomc-neurons-from-birth-to-death
#3
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
#4
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
#5
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/28176381/the-canine-pomc-gene-obesity-in-labrador-retrievers-and-susceptibility-to-diabetes-mellitus
#6
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/28166221/a-molecular-census-of-arcuate-hypothalamus-and-median-eminence-cell-types
#7
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...
February 6, 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
#8
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
#9
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/28099839/trpc5-mediates-acute-leptin-and-serotonin-effects-via-pomc-neurons
#10
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/28028078/ire1%C3%AE-in-pomc-neurons-is-required-for-thermogenesis-and-glycemia
#11
Ting Yao, Zhuo Deng, Yong Gao, Jia Sun, Xingxing Kong, Yiru Huang, Zhenyan He, Yanchao Xu, Yongsheng Chang, Kai-Jiang Yu, Brianna G Findley, Eric D Berglund, Rui-Tao Wang, Hongbo Guo, Hong Chen, Xu Li, Randal J Kaufman, Jianqun Yan, Tiemin Liu, Kevin W Williams
Whether neuronal inositol-requiring enzyme 1(Ire1) is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that pro-opiomelanocortin (Pomc)-specific deficiency of Ire1α accelerated diet-induced obesity concomitant with a decrease in energy expenditure. This hypometabolic phenotype included deficits in thermogenic responses to diet and cold exposure as well as 'beiging' of white adipose tissue. We also demonstrate that loss of Ire1α in Pomc neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity...
December 27, 2016: Diabetes
https://www.readbyqxmd.com/read/28006784/long-term-energy-deficit-in-mice-causes-long-lasting-hypothalamic-alterations-after-recovery
#12
Mathieu Méquinion, Ophélia Le Thuc, Sara Zgheib, David Alexandre, Nicolas Chartrel, Carole Rovère, Pierre Hardouin, Odile Viltart, Christophe Chauveau
Although short-term effects on fasting or energy deficit on hypothalamic neuropeptide circuitries are now better understood, the effects of long-term energy deficit and refeeding remain to be elucidated. We showed that after a long-term energy deficit mice exhibited persistent hypoleptinemia following the refeeding period despite restoration of fat mass, ovarian activity and feeding behavior. We aimed to examine the hypothalamic adaptations after 10 weeks of energy deficit and after 10 further weeks of nutritional recovery...
December 23, 2016: Neuroendocrinology
https://www.readbyqxmd.com/read/28002791/chinese-herb-cinobufagin-reduced-cancer-pain-is-associated-with-increased-peripheral-opioids-by-invaded-cd3-4-8-lymphocytes
#13
Tao Chen, Shenjun Yuan, Xin-Nian Wan, Ling Zhan, Xue-Qin Yu, Jian-Hong Zeng, Hong Li, Wen Zhang, Xiang-Yang Hu, Yi-Fei Ye, Wei Hu
OBJECTIVES: To investigate the mechanism of cinobufagin-reduced cancer pain in mouse cancer pain model and in vitro cell co-culture system. METHODS: Female Kunming mice were randomly divided into 4 groups. One group of animals was set as normal control without any treatment. Other three groups of animals received H22 hepatoma cell inoculation in right hind paw. At day 9 after inoculation, mice in other three groups were injected intraperitoneally once a day for 8 days with the solvent, morphine or cinobufagin, respectively...
December 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27994501/blockade-of-central-glp-1-receptors-deteriorates-the-improvement-of-diabetes-after-ileal-transposition
#14
Weijie Chen, Qianqian Xu, Yiding Xiao, Jiaolin Zhou, Weimin Zhang, Guole Lin, Fengying Gong
Background: The mechanism of improvement of type 2 diabetes mellitus induced by ileal transposition (IT) is undefined. Our aim was to investigate the possible role of central glucagon-like peptide 1 (GLP-1) after IT. Methods: Ninety male diabetic rats were randomly divided into the IT, sham IT (S-IT) and control group. The food intake, glucose metabolism and GLP-1 level were measured. Subsequently, we administered GLP-1 antagonist via lateral brain ventricle cannula to block central GLP-1 receptor, and verified whether the food intake, glucose metabolism changed...
2016: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/27988176/anxiogenic-like-effects-of-fluoxetine-render-adult-male-rats-vulnerable-to-the-effects-of-a-novel-stress
#15
Francisca Gomez, Luis García-García
Fluoxetine (FLX) has paradoxical anxiogenic-like effects during the acute phase of treatment. In adolescent (35d-old) male rats, the stress-like effects induced by short-term (3d-4d) FLX treatment appear to involve up-regulation of paraventricular nucleus (PVN) arginine vasopressin (AVP) mRNA. However, studies on FLX-induced anxiety-like effects in adult rodents are inconclusive. Herein, we sought to study the response of adult male rats (60-65d-old) to a similar FLX treatment, also investigating how the stressful component, inherent to our experimental conditions, contributed to the responses...
February 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27926761/prostaglandin-e2-tumor-necrosis-factor-%C3%AE-and-pro-opiomelanocortin-genes-as-potential-mediators-of-cancer-pain-in-cutaneous-squamous-cell-carcinoma-of-organ-transplant-recipients
#16
Sara Regina Frauenfelder, Sandra Nicole Freiberger, Jan Nico Bouwes Bavinck, Koen D Quint, Roel Genders, Andreas L Serra, Günther F L Hofbauer
No abstract text is available yet for this article.
December 7, 2016: JAMA Dermatology
https://www.readbyqxmd.com/read/27916541/the-orphan-g-protein-coupled-receptor-gpr139-is-activated-by-the-peptides-adrenocorticotropic-hormone-acth-%C3%AE-and-%C3%AE-melanocyte-stimulating-hormone-%C3%AE-msh-and-%C3%AE-msh-and-the-conserved-core-motif-hfrw
#17
Anne Cathrine Nøhr, Mohamed A Shehata, Alexander S Hauser, Vignir Isberg, Jacek Mokrosinski, Kirsten B Andersen, I Sadaf Farooqi, Daniel Sejer Pedersen, David E Gloriam, Hans Bräuner-Osborne
GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well as di-peptides comprised of aromatic amino acids. This led us to hypothesize that GPR139 may be activated by peptides. Sequence alignment of the binding cavities of all class A GPCRs, revealed that the binding pocket of the melanocortin 4 receptor is similar to that of GPR139...
January 2017: Neurochemistry International
https://www.readbyqxmd.com/read/27896569/anti-pituitary-antibodies-against-corticotrophs-in-igg4-related-hypophysitis
#18
Naoko Iwata, Shintaro Iwama, Yoshihisa Sugimura, Yoshinori Yasuda, Kohtaro Nakashima, Seiji Takeuchi, Daisuke Hagiwara, Yoshihiro Ito, Hidetaka Suga, Motomitsu Goto, Ryoichi Banno, Patrizio Caturegli, Teruhiko Koike, Yoshiharu Oshida, Hiroshi Arima
PURPOSE: IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors...
November 28, 2016: Pituitary
https://www.readbyqxmd.com/read/27894398/mir-488-determines-coat-pigmentation-by-down-regulating-the-pigment-producing-gene-pro-opiomelanocortin
#19
H Wang, S Ma, L Xue, Y Li, J Wang, X He, Z Zhu, C Dong
Coat color is a key economic trait in wool- and fur-producing animals. Coat color is controlled by complex mechanisms. Pro-opiomelanocortin (POMC) is a gene involved in pigment formation. Previous studies suggested that miR-488 might target the POMC mRNA. This study aimed to determine whether miR-488 could affect coat color by regulating POMC and to explore the regulatory roles of miR-488 on coat color in mammals. A dual fluorescence report vector containing the 3'-UTR of POMC was built to determine whether miR-488 could post-transcriptionally regulate POMC expression...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27894066/obesity-associated-extracellular-mtdna-activates-central-tgf%C3%AE-pathway-to-cause-blood-pressure-increase
#20
Alberto Ale, Yalin Zhang, Cheng Han, Dongsheng Cai
Hypothalamic inflammation was recently found to mediate obesity-related hypertension, but the responsible upstream mediators remain unexplored. In this study, we show that dietary obesity is associated with extracellular release of mitochondrial DNA (mtDNA) into the cerebrospinal fluid, and that central delivery of mtDNA mimics TGFβ excess to activate downstream signaling pathways. Physiological study reveals that central administration of mtDNA or TGFβ are both sufficient to cause hypertension in mice. Knockout of the TGFβ receptor in pro-opiomelanocortin neurons counteracts the hypertensive effect of not only TGFβ but mtDNA excess, while the hypertensive action of central mtDNA can be blocked pharmacologically by a TGFβ receptor antagonist or genetically by TGFβ receptor knockout...
November 15, 2016: American Journal of Physiology. Endocrinology and Metabolism
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