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https://www.readbyqxmd.com/read/28762947/energy-imbalance-alters-ca-2-handling-and-excitability-of-pomc-neurons
#1
Lars Paeger, Andreas Pippow, Simon Hess, Moritz Paehler, Andreas C Klein, Andreas Husch, Christophe Pouzat, Jens C Brüning, Peter Kloppenburg
Satiety-signaling, pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus play a pivotal role in the regulation of energy homeostasis. Recent studies reported altered mitochondrial dynamics and decreased mitochondria- endoplasmic reticulum contacts in POMC neurons during diet-induced obesity. Since mitochondria play a crucial role in Ca(2+) signaling, we investigated whether obesity alters Ca(2+) handling of these neurons in mice. In diet-induced obesity, cellular Ca(2+) handling properties including mitochondrial Ca(2+) uptake capacity are impaired, and an increased resting level of free intracellular Ca(2+) is accompanied by a marked decrease in neuronal excitability...
August 1, 2017: ELife
https://www.readbyqxmd.com/read/28762946/plasticity-of-calcium-permeable-ampa-glutamate-receptors-in-pro-opiomelanocortin-neurons
#2
Shigetomo Suyama, Alexandra Ralevski, Zhong-Wu Liu, Marcelo O Dietrich, Toshihiko Yada, Stephanie E Simonds, Michael A Cowley, Xiao-Bing Gao, Sabrina Diano, Tamas L Horvath
POMC neurons integrate metabolic signals from the periphery. Here, we show in mice that food deprivation induces a linear current-voltage relationship of AMPAR-mediated excitatory postsynaptic currents (EPSCs) in POMC neurons. Inhibition of EPSCs by IEM-1460, an antagonist of calcium-permeable (Cp) AMPARs, diminished EPSC amplitude in the fed but not in the fasted state, suggesting entry of GluR2 subunits into the AMPA receptor complex during food deprivation. Accordingly, removal of extracellular calcium from ACSF decreased the amplitude of mEPSCs in the fed but not the fasted state...
August 1, 2017: ELife
https://www.readbyqxmd.com/read/28716934/sigma-1-receptors-control-immune-driven-peripheral-opioid-analgesia-during-inflammation-in-mice
#3
Miguel A Tejada, Angeles Montilla-García, Shane J Cronin, Domagoj Cikes, Cristina Sánchez-Fernández, Rafael González-Cano, M Carmen Ruiz-Cantero, Josef M Penninger, José M Vela, José M Baeyens, Enrique J Cobos
Sigma-1 antagonism potentiates the antinociceptive effects of opioid drugs, so sigma-1 receptors constitute a biological brake to opioid drug-induced analgesia. The pathophysiological role of this process is unknown. We aimed to investigate whether sigma-1 antagonism reduces inflammatory pain through the disinhibition of the endogenous opioidergic system in mice. The selective sigma-1 antagonists BD-1063 and S1RA abolished mechanical and thermal hyperalgesia in mice with carrageenan-induced acute (3 h) inflammation...
August 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28699813/prolylcarboxypeptidase-prcp-inhibitors-and-the-therapeutic-uses-thereof-a-patent-review
#4
Thomas H Graham
Prolylcarboxypeptidase (PrCP) is a serine protease that produces or degrades signaling proteins in several important pathways including the renin-angiotensin system (RAS), kallikrein-kinin system (KKS) and pro-opiomelanocortin (POMC) system. PrCP has the potential to be a therapeutic target for cardiovascular, inflammatory and metabolic diseases. Numerous classes of PrCP inhibitors have been developed by rational drug design and from high-throughput screening hits. These inhibitors have been tested in mouse models to assess their potential as new therapeutics...
July 12, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28694769/hypothalamic-integration-of-metabolic-endocrine-and-circadian-signals-in-fish-involvement-in-the-control-of-food-intake
#5
REVIEW
María J Delgado, José M Cerdá-Reverter, José L Soengas
The regulation of food intake in fish is a complex process carried out through several different mechanisms in the central nervous system (CNS) with hypothalamus being the main regulatory center. As in mammals, a complex hypothalamic circuit including two populations of neurons: one co-expressing neuropeptide Y (NPY) and Agouti-related peptide (AgRP) and the second one population co-expressing pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) is involved in the integration of information relating to food intake control...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28649723/distribution-and-female-reproductive-state-differences-in-orexigenic-and-anorexigenic-neurons-in-the-brain-of-the-mouth-brooding-african-cichlid-fish-astatotilapia-burtoni
#6
Danielle T Porter, David A Roberts, Karen P Maruska
Integration of reproduction and metabolism is necessary for species survival. While the neural circuits controlling energy homeostasis are well-characterized, the signals controlling the relay of nutritional information to the reproductive axis are less understood. The cichlid fish Astatotilapia burtoni is ideal for studying the neural regulation of feeding and reproduction because females cycle between a feeding gravid state and a period of forced starvation while they brood developing young inside their mouths...
October 1, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28632132/antagonistic-modulation-of-npy-agrp-and-pomc-neurons-in-the-arcuate-nucleus-by-noradrenalin
#7
Lars Paeger, Ismene Karakasilioti, Janine Altmüller, Peter Frommolt, Jens Brüning, Peter Kloppenburg
In the arcuate nucleus of the hypothalamus (ARH) satiety signaling (anorexigenic) pro-opiomelanocortin (POMC)-expressing and hunger signaling (orexigenic) agouti-related peptide (AgRP)-expressing neurons are key components of the neuronal circuits that control food intake and energy homeostasis. Here, we assessed whether the catecholamine noradrenalin directly modulates the activity of these neurons in mice. Perforated patch clamp recordings showed that noradrenalin changes the activity of these functionally antagonistic neurons in opposite ways, increasing the activity of the orexigenic NPY/AgRP neurons and decreasing the activity of the anorexigenic POMC neurons...
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28617052/neotomodon-alstoni-mice-present-sex-differences-between-lean-and-obese-in-daily-hypothalamic-leptin-signaling
#8
Moisés Pérez-Mendoza, Dalia Luna-Moreno, Agustín Carmona-Castro, Hugo A Rodríguez-Guadarrama, Luis M Montoya-Gómez, Mauricio Díaz-Muñoz, Manuel Miranda-Anaya
This article compared the effects of spontaneous obesity on the daily profile in the relative amount of the leptin receptor (LepRb), and its output. That is the precursor Pro-opiomelanocortin (POMC) over a 24-hour period and compared with differences in locomotion and food intake in periods of artificial light. Differences between lean and obese mice were examined, as were sex differences. Body weight, food intake and locomotor activity were monitored in freely moving lean and obese mice. Hypothalamic tissue was collected at 5 h, 10 h, 15 h, 19 h and 24 h...
June 15, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28610922/central-administration-of-glp-1-and-gip-decreases-feeding-in-mice
#9
Cherl NamKoong, Min Sun Kim, Byeong-Tak Jang, Young Hee Lee, Young-Min Cho, Hyung Jin Choi
Glucagon-like peptide-1 amide (GLP-1) and gastric inhibitory polypeptide (GIP) are incretin hormones regulating energy metabolism. GLP-1 and GIP combination is suggested as a promising therapeutic strategy for treatment of obesity and diabetes. However, the neuronal mechanisms are not yet investigated. In the present study, we investigated the role of central GLP-1 and GIP in regulation of body weight homeostasis. The effect of GLP-1 with GIP on food intake, body weight, locomotor activity were determined following intracerebroventricular (ICV) administration of GLP-1 and/or GIP in mice...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28575455/adolescent-alcohol-exposure-induced-changes-in-alpha-melanocyte-stimulating-hormone-and-neuropeptide-y-pathways-via-histone-acetylation-in-the-brain-during-adulthood
#10
Dadasaheb M Kokare, Evan J Kyzar, Huaibo Zhang, Amul J Sakharkar, Subhash C Pandey
Background: Adolescent intermittent ethanol (AIE) exposure causes long-lasting alterations in brain epigenetic mechanisms. Melanocortin and neuropeptide Y (NPY) signaling interact and are affected by ethanol exposure in the brain. Here, the persistent effects of AIE on alpha-melanocyte stimulating hormone (α-MSH), melanocortin 4 receptor (MC4R) and NPY expression and their regulation by histone acetylation mechanisms were investigated in adulthood. Methods: Male rats were exposed to AIE (2 g/kg, i...
May 31, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28572791/hunger-and-satiety-gauge-reward-sensitivity
#11
REVIEW
Ryan Michael Cassidy, Qingchun Tong
Many of the neurocircuits and hormones known to underlie the sensations of hunger and satiety also substantially alter the activity of the dopaminergic reward system. Much interest lies in the ways that hunger, satiety, and reward tie together, as the epidemic of obesity seems tied to the recent development and mass availability of highly palatable foods. In this review, we will first discuss the basic neurocircuitry of the midbrain and basal forebrain reward system. We will elaborate how several important mediators of hunger-the agouti-related protein neurons of the arcuate nucleus, the lateral hypothalamic nucleus, and ghrelin-enhance the sensitivity of the dopaminergic reward system...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28552562/the-central-anorexigenic-mechanism-of-amylin-in-japanese-quail-coturnix-japonica-involves-pro-opiomelanocortin-calcitonin-receptor-and-the-arcuate-nucleus-of-the-hypothalamus
#12
Jingwei Yuan, Elizabeth R Gilbert, Mark A Cline
Amylin is a 37-amino acid peptide hormone that exerts anorexigenic effects in humans and animals. We demonstrated that central injection of amylin into chicks affected feeding and related behaviors via the hypothalamus and brainstem, although the molecular mechanisms remained elusive. Thus, the objective of this study was to investigate the molecular mechanisms underlying anorexigenic effects of amylin in 7 day-old Japanese quail. Food but not water intake was reduced after intracerebroventricular amylin injection, and the behavior analysis indicated that this was associated with decreased food pecks and preening...
August 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28500249/maternal-high-fat-diet-induces-metabolic-stress-response-disorders-in-offspring-hypothalamus
#13
Long The Nguyen, Sonia Saad, Yi Tan, Carol Pollock, Hui Chen
Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect.  In this study, we show that offspring born to HFD-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning...
May 12, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28489068/tnf%C3%AE-drives-mitochondrial-stress-in-pomc-neurons-in-obesity
#14
Chun-Xia Yi, Marc Walter, Yuanqing Gao, Soledad Pitra, Beata Legutko, Stefanie Kälin, Clarita Layritz, Cristina García-Cáceres, Maximilian Bielohuby, Martin Bidlingmaier, Stephen C Woods, Alexander Ghanem, Karl-Klaus Conzelmann, Javier E Stern, Martin Jastroch, Matthias H Tschöp
Consuming a calorically dense diet stimulates microglial reactivity in the mediobasal hypothalamus (MBH) in association with decreased number of appetite-curbing pro-opiomelanocortin (POMC) neurons; whether the reduction in POMC neuronal function is secondary to the microglial activation is unclear. Here we show that in hypercaloric diet-induced obese mice, persistently activated microglia in the MBH hypersecrete TNFα that in turn stimulate mitochondrial ATP production in POMC neurons, promoting mitochondrial fusion in their neurites, and increasing POMC neuronal firing rates and excitability...
May 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28462073/heterogeneity-of-hypothalamic-pro-opiomelanocortin-expressing-neurons-revealed-by-single-cell-rna-sequencing
#15
Brian Y H Lam, Irene Cimino, Joseph Polex-Wolf, Sara Nicole Kohnke, Debra Rimmington, Valentine Iyemere, Nicholas Heeley, Chiara Cossetti, Reiner Schulte, Luis R Saraiva, Darren W Logan, Clemence Blouet, Stephen O'Rahilly, Anthony P Coll, Giles S H Yeo
OBJECTIVE: Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. METHODS: Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. RESULTS: Of 163 neurons, 118 expressed high levels of Pomc with little/no Agrp expression and were considered "canonical" POMC neurons (P(+))...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28455431/hypothalamic-effects-of-neonatal-diet-reversible-and-only-partially-leptin-dependent
#16
Luba Sominsky, Ilvana Ziko, Thai-Xinh Nguyen, Julie Quach, Sarah J Spencer
Early life diet influences metabolic programming, increasing the risk for long-lasting metabolic ill health. Neonatally overfed rats have an early increase in leptin that is maintained long term and is associated with a corresponding elevation in body weight. However, the immediate and long-term effects of neonatal overfeeding on hypothalamic anorexigenic pro-opiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY) circuitry, and if these are directly mediated by leptin, have not yet been examined...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28450851/regulation-of-agouti-related-protein-and-pro-opiomelanocortin-gene-expression-in-the-avian-arcuate-nucleus
#17
REVIEW
Timothy Boswell, Ian C Dunn
The arcuate nucleus is generally conserved across vertebrate taxa in its neuroanatomy and neuropeptide expression. Gene expression of agouti-related protein (AGRP), neuropeptide Y (NPY), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART) has been established in the arcuate nucleus of several bird species and co-localization demonstrated for AGRP and NPY. The proteins encoded by these genes exert comparable effects on food intake in birds after central administration to those seen in other vertebrates, with AGRP and NPY being orexigenic and CART and α-melanocyte-stimulating hormone anorexigenic...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28424580/the-role-of-microrna-in-the-modulation-of-the-melanocortinergic-system
#18
REVIEW
Adel Derghal, Mehdi Djelloul, Jérôme Trouslard, Lourdes Mounien
The central control of energy balance involves a highly regulated neuronal network within the hypothalamus and the dorsal vagal complex. In these structures, pro-opiomelanocortin (POMC) neurons are known to reduce meal size and to increase energy expenditure. In addition, leptin, a peripheral signal that relays information regarding body fat content, modulates the activity of melanocortin pathway neurons including POMC-, Agouti-related peptide (AgRP)/Neuropeptide Y (NPY)-, melanocortin receptors (MC3R and MC4R)-expressing neurons...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28403939/melanocortin-4-receptor-is-not-required-for-estrogenic-regulations-on-energy-homeostasis-and-reproduction
#19
Pingwen Xu, Liangru Zhu, Kenji Saito, Yongjie Yang, Chunmei Wang, Yanlin He, Xiaofeng Yan, Ilirjana Hyseni, Qingchun Tong, Yong Xu
BACKGROUND: Brain estrogen receptor-α (ERα) is essential for estrogenic regulation of energy homeostasis and reproduction. We previously showed that ERα expressed by pro-opiomelanocortin (POMC) neurons mediates estrogen's effects on food intake, body weight, negative regulation of hypothalamic-pituitary-gonadal axis (HPG axis) and fertility. RESULTS AND CONCLUSIONS: We report here that global deletion of a key downstream receptor for POMC peptide, the melanocortin 4 receptor (MC4R), did not affect normal negative feedback regulation of estrogen on the HPG axis, estrous cyclicity and female fertility...
May 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28385803/insulin-receptor-signaling-in-pomc-but-not-agrp-neurons-controls-adipose-tissue-insulin-action
#20
Andrew C Shin, Nika Filatova, Claudia Lindtner, Tiffany Chi, Seta Degann, Douglas Oberlin, Christoph Buettner
Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and through signaling in the central nervous system by dampening sympathetic outflow to the adipose tissue. Here we examined the role of insulin signaling in agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating hepatic and adipose tissue insulin action...
June 2017: Diabetes
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