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https://www.readbyqxmd.com/read/28739551/the-description-of-a-new-case-with-proopiomelanocortin-pomc-deficiency-an-increasingly-important-diagnosis-to-make
#1
Semra Çetinkaya, Tülay Güran, Erdal Kurnaz, Melikşah Keskin, Elif Sağsak, Senay Savaş Erdeve, Jenifer P Suntharalingham, Federica Buonocore, John Achermann, Zehra Aycan
International surveillance data suggests a worldwide epidemic of pediatric obesity regardless of geographic, socioeconomic, racial and ethnic factors. Reversing this epidemic of pediatric obesity will require recognition and understanding of the pathophysiology of the condition to enable us to develop novel therapies as well as taking measures to shift social attitudes and public policies at a global level. Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder of early-onset obesity, which has increased our insight into the important role of the leptin-melanocortin pathway in energy balance...
July 24, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28710116/expression-and-mutational-status-of-usp8-in-tumors-causing-ectopic-acth-secretion-syndrome
#2
Luis Gustavo Pérez-Rivas, Andrea Oßwald, Thomas Knösel, Kristin Lucia, Christian Schaaf, Michael Hristov, Julia Fazel, Thomas Kirchner, Felix Beuschlein, Martin Reincke, Marily Theodoropoulou
The ectopic ACTH secretion syndrome (EAS) is the clinical consequence of the paraneoplastic secretion of ACTH by non-pituitary tumors. The mechanisms responsible for the pathogenesis of these tumors are still unknown. Recently, we and others detected hotspot heterozygous driver mutations in the gene coding for the ubiquitin-specific protease 8 (USP8) in almost half of ACTH-secreting pituitary corticotroph tumors causing Cushing's disease. Mutant USP8 was also found to stimulate proopiomelanocortin (POMC) transcription and ACTH synthesis...
July 14, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28699813/prolylcarboxypeptidase-prcp-inhibitors-and-the-therapeutic-uses-thereof-a-patent-review
#3
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/28696162/physiological-and-brain-alterations-produced-by-high-fat-diet-in-male-and-female-rats-can-be-modulated-by-increased-levels-of-estradiol-during-critical-periods-of-development
#4
Beatriz Carrillo, Paloma Collado, Francisca Díaz, Julie A Chowen, Mª Ángeles Pérez-Izquierdo, Helena Pinos
BACKGROUND: Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development. OBJECTIVE: Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition. METHODS: Twenty-four male and 24 female Wistar rats were submitted to a HFD (34...
July 11, 2017: Nutritional Neuroscience
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/28690493/emerging-signaling-pathway-in-arcuate-feeding-related-neurons-role-of-the-acbd7
#6
REVIEW
Damien Lanfray, Denis Richard
The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART) and the neurons co-localizing agouti-related peptide (AgRP), neuropeptide Y (NPY), and gamma-aminobutyric acid (GABA). These neurons are part of the leptin-melanocortin pathway, whose role is key in energy balance regulation...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28687926/atat1-is-essential-for-regulation-of-homeostasis-retaining-cellular-responses-in-corticotrophs-along-hypothalamic-pituitary-adrenal-axis
#7
Takashi Nakakura, Takeshi Suzuki, Seiji Torii, Anshin Asano-Hoshino, Yoko Nekooki-Machida, Hideyuki Tanaka, Kenjiro Arisawa, Yoshimi Nishijima, Takao Susa, Tomoki Okazaki, Yoshiko Kiuchi, Haruo Hagiwara
The production and secretion of adrenocorticotropin, a proopiomelanocortin (POMC)-derived hormone, by corticotrophs in the anterior pituitary, is regulated by corticotrophin-releasing hormone (CRH) and glucocorticoids. We have previously demonstrated that adrenalectomy induces α-tubulin N-acetyltransferase 1 (ATAT1) expression and α-tubulin acetylation in corticotrophs. However, the regulatory mechanism of ATAT1 expression and the function of acetylated microtubules in corticotrophs are unclear. Here, we analyze the effect of CRH or dexamethasone on Atat1 expression in the mouse corticotroph AtT20 cell line...
July 7, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28684967/cyclocarya-paliurus-batal-ijinskaja-aqueous-extract-cpae-ameliorates-obesity-by-improving-insulin-signaling-in-the-hypothalamus-of-a-metabolic-syndrome-rat-model
#8
Guangyuan Xu, Hisae Yoshitomi, Wen Sun, Xuan Guo, Lili Wu, Xiangyu Guo, Lingling Qin, Yixin Fan, Tunhai Xu, Tonghua Liu, Ming Gao
BACKGROUND: Antiobesity drugs may not be optimal for treating obesity. However novel antiobesity agents, especially those derived from natural products, may be suitable. Therefore, we investigated the effects and mechanisms of Cyclocarya paliurus (CP) aqueous extract (CPAE) on obesity. METHODS: SHR.Cg-Leprcp/NDmcr (SHR/cp) rats were used as a model of obesity and metabolic syndrome. Experimental animals were allocated into two groups-control and CPAE (0.5 g/kg)-for a 7-week treatment period...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28675783/insulin-and-leptin-excite-anorexigenic-proopiomelanocortin-neurons-via-activation-of-trpc5-channels
#9
REVIEW
Jian Qiu, Edward J Wagner, Oline K Rønnekleiv, Martin J Kelly
Proopiomelanocortin (POMC) neurons within the hypothalamic arcuate nucleus are vital anorexigenic neurons. Both the insulin receptor and leptin receptor are coupled to activation of phosphatidylinositide-3 kinase (PI3K) to regulate multiple functions that increase POMC neuronal excitability. Using whole-cell recording in several mammalian species, we have found that both insulin and leptin depolarized POMC neurons via activation of TRPC5 channels. TRPC5 channels have been rigorously characterized as the downstream effector based on their biophysical properties, pharmacological profile and localization by immunocytochemistry and scRT-PCR...
July 4, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28667175/the-relevance-of-agrp-neuron-derived-gaba-inputs-to-pomc-neurons-differs-for-spontaneous-and-evoked-release
#10
Andrew R Rau, Shane T Hentges
Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. Spontaneous GABA-mediated inhibitory postsynaptic currents (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell-type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent VAMP2-dependent vesicle fusion...
June 30, 2017: Journal of Neuroscience: the Official Journal of the Society for 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
#11
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...
June 26, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28647359/mild-hypothermia-ameliorates-muscle-wasting-in-septic-rats-associated-with-hypothalamic-ampk-induced-autophagy-and-neuropeptides
#12
Chun Cao, Tao Gao, Minhua Cheng, Fengchan Xi, Chenyan Zhao, Wenkui Yu
Sepsis, always developing muscle wasting, contributes to serious complications and mortality. Mild hypothermia has been reported to have protective effects on the prognosis of septic patients. However, the underlying mechanisms remain unclear. We therefore hypothesized that mild hypothermia could ameliorate muscle wasting during sepsis and whether it was associated with hypothalamus AMPK-induced autophagy and neuropeptides. Adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647318/expression-of-genes-for-melanotropic-peptides-and-their-receptors-for-morphological-color-change-in-goldfish-carassius-auratus
#13
Kanta Mizusawa, Yutaka Yamamura, Satoshi Kasagi, José Miguel Cerdá-Reverter, Akiyoshi Takahashi
To evaluate the association of the melanotropic peptides and their receptors for morphological color change, we investigated the effects of changes in background color, between white and black, on xanthophore density in the scales and expression levels of genes for hormonal peptides and corresponding receptors (MCH-R2, MC1R, and MC5R) in goldfish (Carassius auratus). The xanthophore density in both dorsal and ventral scales increased after transfer from a white to black background. However, xanthophore density in dorsal scales increased after transfer from a black to white background, and that of ventral scales decreased after transfer from a black-to-black background, which served as the control...
June 21, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28645299/programming-of-mouse-obesity-by-maternal-exposure-to-concentrated-ambient-fine-particles
#14
Minjie Chen, Xiaoke Wang, Ziying Hu, Huifen Zhou, Yanyi Xu, Lianglin Qiu, Xiaobo Qin, Yuhao Zhang, Zhekang Ying
BACKGROUND: Many diseases including obesity may originate through alterations in the early-life environment that interrupts fetal development. Increasing evidence has shown that exposure to ambient fine particles (PM2.5) is associated with abnormal fetal development. However, its long-term metabolic effects on offspring have not been systematically investigated. RESULTS: To determine if maternal exposure to PM2.5 programs offspring obesity, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM2...
June 23, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28632132/antagonistic-modulation-of-npy-agrp-and-pomc-neurons-in-the-arcuate-nucleus-by-noradrenalin
#15
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/28629513/erythropoietin-and-hypothalamic-pituitary-axis
#16
Soumyadeep Dey, Constance T Noguchi
Erythropoietin (EPO), known primarily for its erythropoietic activity, is commonly used clinically to treat anemia of chronic kidney disease. However, the expression of EPO receptor (EpoR) beyond erythroid tissue provides for potential extrahematopoietic effects of EPO, including EPO regulation of metabolic homeostasis (Zhang et al., 2014). Small clinical studies have shown that EPO treatment in patients with end-stage renal disease improved glycemic control and insulin sensitivity. Studies in animal models have shown that EPO regulation of metabolism is mainly attributed to its response in fat, and the hypothalamus-pituitary axis (Dey et al...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28628102/regulation-of-body-weight-and-energy-homeostasis-by-neuronal-cell-adhesion-molecule-1
#17
Thomas Rathjen, Xin Yan, Natalia L Kononenko, Min-Chi Ku, Kun Song, Leiron Ferrarese, Valentina Tarallo, Dmytro Puchkov, Gaga Kochlamazashvili, Sebastian Brachs, Luis Varela, Klara Szigeti-Buck, Chun-Xia Yi, Sonja C Schriever, Sudhir Gopal Tattikota, Anne Sophie Carlo, Mirko Moroni, Jan Siemens, Arnd Heuser, Louise van der Weyden, Andreas L Birkenfeld, Thoralf Niendorf, James F A Poulet, Tamas L Horvath, Matthias H Tschöp, Matthias Heinig, Mirko Trajkovski, Volker Haucke, Matthew N Poy
Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure...
August 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28627418/alterations-in-neuronal-control-of-body-weight-and-anxiety-behavior-by-glutathione-peroxidase-4-deficiency
#18
Sonja C Schriever, Annemarie Zimprich, Katrin Pfuhlmann, Peter Baumann, Florian Giesert, Valentina Klaus, Dhiraj G Kabra, Ulrich Hafen, Artem Romanov, Matthias H Tschöp, Wolfgang Wurst, Marcus Conrad, Sabine M Hölter, Daniela Vogt Weisenhorn, Paul T Pfluger
Elevated levels of oxidative stress and neuronal inflammation in the hypothalamus or ventral midbrain, respectively, represent common denominators for obesity and Parkinson's Disease (PD). However, little is known about defense mechanisms that protect neurons in these regions from oxidative damage. Here, we aimed to assess whether murine Gpx4, a crucial antioxidant enzyme that protects neurons from membrane damage and ferroptosis, is critical for the protection from neuronal inflammation in two distinct pathophysiologic diseases, namely metabolic dysfunction in diet-induced obesity or PD...
June 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28623340/adenovirus-mediated-suppression-of-hypothalamic-glucokinase-affects-feeding-behavior
#19
Romina María Uranga, Carola Millán, María José Barahona, Antonia Recabal, Magdiel Salgado, Fernando Martinez, Patricio Ordenes, Roberto Elizondo-Vega, Fernando Sepúlveda, Elena Uribe, María de Los Ángeles García-Robles
Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regulation of energy homeostasis. Tanycytes have extended cell processes that contact the feeding-regulating neurons in the AN, particularly, agouti-related protein (AgRP), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) neurons...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622065/leptin-gene-transfer-improves-symptoms-of-type-2-diabetic-mice-by-regulating-leptin-signaling-pathway-and-insulin-resistance-of-peripheral-tissues
#20
Lan Xiang, Jing Li, Qian Wang, Ruiqi Tang, Jianhua Qi
The leptin gene was transferred into the liver of streptozocin- and high fat diet-induced type 2 diabetic (T2D) mice by hydrodynamic-based gene delivery. The food intake, water consumption, glucose concentration, and triglyceride and total cholesterol levels of T2D mice were significantly decreased. Meanwhile, plasma leptin was remarkably increased after gene transfer for 2, 3, 5, and 7 days, while plasma adiponectin was also significantly increased at day 2. To understand the mechanism of action of leptin on T2D mice, gene expressions related to glycometabolism and energy metabolism in the liver, epididymal adipose tissue, hypothalamus, and muscle were measured...
June 15, 2017: Human Gene Therapy
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