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Pro-opiomelanocortin

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https://www.readbyqxmd.com/read/28350524/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-obesity
#1
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Shanghai Chen, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Feifan Guo
ATF4 (activating transcription factor 4) is an important transcription factor that has many biological functions, while its role in hypothalamic POMC (pro-opiomelanocortin-alpha) neurons in the regulation of energy homeostasis has not been explored. We recently discovered that mice with an Atf4 deletion specific to POMC neurons (PAKO mice) are lean and have higher energy expenditure. Furthermore, these mice are resistant to high-fat diet (HFD)-induced obesity and obesity-related metabolic disorders. Mechanistically, we found the expression of ATG5 (autophagy related 5) is upregulated in POMC neurons of PAKO mice, and ATF4 regulates ATG5 expression by binding directly to its promoter...
March 28, 2017: Autophagy
https://www.readbyqxmd.com/read/28325732/whey-protein-effects-on-energy-balance-link-the-intestinal-mechanisms-of-energy-absorption-with-adiposity-and-hypothalamic-neuropeptide-gene-expression
#2
Kanishka N Nilaweera, Raul Cabrera-Rubio, John R Speakman, Paula M O' Connor, AnneMarie McAuliffe, Caitriona M Guinane, Elaine Lawton, Fiona Crispie, Mònica Aguilera, Maurice Stanley, Serena Boscaini, Susan Joyce, Silvia Melgar, John F Cryan, Paul D Cotter
We tested the hypothesis that dietary whey protein isolate (WPI) affects the intestinal mechanisms related to energy absorption and that the resulting energy deficit is compensated by changes in energy balance to support growth. C57BL/6 mice were provided a diet enriched with WPI with varied sucrose content, and the impact on energy balance related parameters were investigated. As part of a high sucrose diet, WPI reduced the hypothalamic expression of pro-opiomelanocortin gene expression and increased energy intake...
March 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323972/neurosecretory-protein-gl-a-hypothalamic-small-secretory-protein-participates-in-energy-homeostasis-in-male-mice
#3
Daichi Matsuura, Kenshiro Shikano, Takaya Saito, Eiko Iwakoshi-Ukena, Megumi Furumitsu, Yuta Ochi, Manami Sato, George E Bentley, Lance J Kriegsfeld, Kazuyoshi Ukena
We have recently identified a novel cDNA encoding a small secretory protein termed neurosecretory protein GL (NPGL) from the avian hypothalamus. In chicks, NPGL increases body weight gain without affecting food intake. A database search reveals that NPGL is conserved throughout vertebrates. However, the central distribution and functional role of NPGL remains to be elucidated in mammals. In this study, we identified the precursor cDNA encoding NPGL from the mouse hypothalamus. Quantitative RT-PCR and morphological analyses revealed that NPGL precursor mRNA is robustly expressed in the mediobasal hypothalamus with NPGL neurons specifically localized to the lateroposterior part of the arcuate nucleus in the hypothalamus...
March 17, 2017: Endocrinology
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
#4
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/28274841/role-of-the-brain-melanocortins-in-blood-pressure-regulation
#5
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
#6
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/28214331/pomc-maintains-tumor-initiating-properties-of-tumor-tissue-derived-long-term-cultured-breast-cancer-stem-cells
#7
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
#8
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
#9
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
#10
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
#11
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...
March 7, 2017: Cell Metabolism
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...
March 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28166221/a-molecular-census-of-arcuate-hypothalamus-and-median-eminence-cell-types
#13
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
#14
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
#15
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
#16
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
#17
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...
March 2017: Diabetes
https://www.readbyqxmd.com/read/28006784/long-term-energy-deficit-in-mice-causes-long-lasting-hypothalamic-alterations-after-recovery
#18
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
#19
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
#20
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
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