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Pro-opiomelanocortin

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https://www.readbyqxmd.com/read/29226825/desacetyl-%C3%AE-melanocyte-stimulating-hormone-and-%C3%AE-melanocyte-stimulating-hormone-are-required-to-regulate-energy-balance
#1
Kathleen G Mountjoy, Alexandre Caron, Kristina Hubbard, Avik Shome, Angus C Grey, Bo Sun, Sarah Bould, Martin Middleditch, Beau Pontré, Ailsa McGregor, Paul W R Harris, Renata Kowalczyk, Margaret A Brimble, Rikus Botha, Karen M L Tan, Sarah J Piper, Christina Buchanan, Syann Lee, Anthony P Coll, Joel K Elmquist
OBJECTIVE: Regulation of energy balance depends on pro-opiomelanocortin (POMC)-derived peptides and melanocortin-4 receptor (MC4R). Alpha-melanocyte stimulating hormone (α-MSH) is the predicted natural POMC-derived peptide that regulates energy balance. Desacetyl-α-MSH, the precursor for α-MSH, is present in brain and blood. Desacetyl-α-MSH is considered to be unimportant for regulating energy balance despite being more potent (compared with α-MSH) at activating the appetite-regulating MC4R in vitro...
November 24, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29207922/effect-of-steady-state-methadone-on-high-fructose-corn-syrup-consumption-in-rats
#2
Stephen Daniels, Mick Pratt, Yan Zhou, Francesco Leri
Patients undergoing methadone maintenance treatment self-report enhanced preferences for, and excessive consumption of, foods rich in sugar. However, it is unclear whether these are direct pharmacological effects of methadone or the consequences of metabolic dysfunctions induced by addiction to illicit opiates. Hence, the current study in drug-naïve male Sprague-Dawley rats explored the effects of steady-state methadone delivered by osmotic mini-pumps (13 days; 0, 10, 30 mg/kg/day) on consumption of rat chow and a palatable, sweet, liquid high fructose corn syrup solution...
December 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29184506/recent-advances-in-the-cellular-and-molecular-mechanisms-of-hypothalamic-neuronal-glucose-detection
#3
Xavier Fioramonti, Chloé Chrétien, Corinne Leloup, Luc Pénicaud
The hypothalamus have been recognized for decades as one of the major brain centers for the control of energy homeostasis. This area contains specialized neurons able to detect changes in nutrients level. Among them, glucose-sensing neurons use glucose as a signaling molecule in addition to its fueling role. In this review we will describe the different sub-populations of glucose-sensing neurons present in the hypothalamus and highlight their nature in terms of neurotransmitter/neuropeptide expression. This review will particularly discuss whether pro-opiomelanocortin (POMC) neurons from the arcuate nucleus are directly glucose-sensing...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29180108/palmitate-induces-neuroinflammation-er-stress-and-pomc-mrna-expression-in-hypothalamic-mhypoa-pomc-gfp-neurons-through-novel-mechanisms-that-are-prevented-by-oleate
#4
Erika K Tse, Denise D Belsham
Dietary fats can modulate brain function. How free fatty acids (FFAs) alter hypothalamic pro-opiomelanocortin (POMC) neurons remain undefined. The saturated FFA, palmitate, increased neuroinflammatory and ER stress markers, as well as Pomc mRNA levels, but did not affect insulin signaling, in mHypoA-POMC/GFP-2 neurons. This effect was mediated through the MAP kinases JNK and ERK. Further, the increase in Pomc was dependent on palmitoyl-coA synthesis, but not de novo ceramide synthesis, as inhibition of SPT enhanced palmitate-induced Pomc expression, while methylpalmitate had no effect...
November 24, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29174000/deficiency-of-leptin-receptor-in-myeloid-cells-disrupts-hypothalamic-metabolic-circuits-and-causes-body-weight-increase
#5
Yuanqing Gao, Andrés Vidal-Itriago, Irina Milanova, Nikita L Korpel, Martin J Kalsbeek, Robby Zachariah Tom, Andries Kalsbeek, Susanna M Hofmann, Chun-Xia Yi
OBJECTIVE: Leptin is a cytokine produced by adipose tissue that acts mainly on the hypothalamus to regulate appetite and energy homeostasis. Previous studies revealed that the leptin receptor is expressed not only in neurons, but also in glial cells. Microglia are resident immune cells in the brain that play an essential role in immune defense and neural network development. Previously we reported that microglial morphology and cytokine production are changed in the leptin receptor deficient db/db mouse, suggesting that leptin's central effects on metabolic control might involve signaling through microglia...
November 9, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29168299/17%C3%AE-estradiol-acts-through-hypothalamic-pro-opiomelanocortin-expressing-neurons-to-reduce-feeding-behavior
#6
Frederik J Steyn, Shyuan T Ngo, Vicky Ping Chen, Lora C Bailey-Downs, Teresa Y Xie, Martin Ghadami, Stephen Brimijoin, Willard M Freeman, Marcelo Rubinstein, Malcolm J Low, Michael B Stout
Weight loss is an effective intervention for diminishing disease burden in obese older adults. Pharmacological interventions that reduce food intake and thereby promote weight loss may offer effective strategies to reduce age-related disease. We previously reported that 17α-estradiol (17α-E2) administration elicits beneficial effects on metabolism and inflammation in old male mice. These observations were associated with reduced calorie intake. Here, we demonstrate that 17α-E2 acts through pro-opiomelanocortin (Pomc) expression in the arcuate nucleus (ARC) to reduce food intake and body mass in mouse models of obesity...
November 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/29164831/udenafil-a-phosphodiesterase-5-inhibitor-reduces-body-weight-in-high-fat-fed-mice
#7
Seong Yul Ryu, Yoon Jung Choi, So Young Park, Jong Yeon Kim, Yong Dae Kim, Yong Woon Kim
PURPOSE: High-fat (HF) feeding induces hypothalamic leptin resistance via the activation of toll-like receptor 4 (TLR4). TLR4 deficiency confers resistance to diet-induced obesity. Udenafil, an anti-impotence drug, inhibits TLR4 in airway epithelial cells in vitro. In this study, we evaluated whether udenafil suppressed the hypothalamic expression of TLR4 and reduced body weight. MATERIALS AND METHODS: The hypothalamic expression of TLR4, phosphodiesterase 5 (PDE5), nuclear factor-κB (NF-κB), and myeloid differentiation primary response gene 88 (Myd88) was analyzed by real-time polymerase chain reaction after treating mice for 2 days with udenafil (0, 12, 120, or 600 μg/d)...
November 16, 2017: World Journal of Men's Health
https://www.readbyqxmd.com/read/29155136/adipose-tissue-and-reproductive-health
#8
REVIEW
Hannah Mathew, V Daniel Castracane, Christos Mantzoros
The understanding of adipose tissue role has evolved from that of a depot energy storage organ to a dynamic endocrine organ. While genetics, sexual phenotype and sex steroids can impact the mass and distribution of adipose tissue, there is a counter-influence of white adipocytes on reproduction. This primarily occurs via the secretion of adipokines, the most studied of which- leptin and adiponectin- are highlighted in this article. Leptin, the "satiety hormone" primarily acts on the hypothalamus via pro-opiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AgRP) NPY neurons to translate acute changes in nutrition and energy expenditure, as well as chronic adipose accumulation into changes in appetite and potentially mediate insulin resistance via shared pathway and notably impacting reproductive health via influence on GnRH secreting neurons...
November 16, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29142191/immune-neuroendocrine-interactions-evolution-ecology-and-susceptibility-to-illness
#9
Johanna M C Blom, Enzo Ottaviani
The integration between immune and neuroendocrine systems is crucial for maintaining homeostasis from invertebrates to humans. In the first, the phagocytic cell, i.e., the immunocyte, is the main actor, while in the latter, the principle player is the lymphocyte. Immunocytes are characterized by the presence of pro-opiomelanocortin (POMC) peptides, CRH, and other molecules that display a significant similarity to their mammalian counterparts regarding their functions, as both are mainly involved in fundamental functions such as immune (chemotaxis, phagocytosis, cytotoxicity, etc...
November 16, 2017: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/29123503/hyperleptinemia-in-neonatally-overfed-female-rats-does-not-dysregulate-feeding-circuitry
#10
Ilvana Ziko, Luba Sominsky, Thai-Xinh Nguyen, Kit-Yi Yam, Simone De Luca, Aniko Korosi, Sarah J Spencer
Neonatal overfeeding during the first weeks of life in male rats is associated with a disruption in the peripheral and central leptin systems. Neonatally overfed male rats have increased circulating leptin in the first 2 weeks of life, which corresponds to an increase in body weight compared to normally fed counterparts. These effects are associated with a short-term disruption in the connectivity of neuropeptide Y (NPY), agouti-related peptide (AgRP), and pro-opiomelanocortin (POMC) neurons within the regions of the hypothalamus responsible for control of energy balance and food intake...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29069975/the-combination-of-escitalopram-and-aripiprazole-investigation-of-psychomotor-effects-in-rats
#11
Roger Hudson, Yan Zhou, Francesco Leri
Pre-clinical and clinical evidence suggests that the antidepressant efficacy of the selective serotonin reuptake inhibitor escitalopram can be enhanced by the dopamine and serotonin partial agonist aripiprazole. Given the range of possible neurochemical interactions between these drugs, the current study investigated whether aripiprazole alters the hedonic and psychomotor effects of escitalopram. Male Sprague Dawley rats ( n=116) received 10 mg/kg/day escitalopram (subcutaneous), 2 mg/kg/day aripiprazole (subcutaneous), or combined aripiprazole + escitalopram, and were tested for consumption of incentive nutritional stimuli (high-fructose corn syrup and chow), stereotypy and locomotor activity...
October 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29059347/sim1-neurons-are-sufficient-for-mc4r-mediated-sexual-function-in-male-mice
#12
Erin Semple, Jennifer W Hill
Sexual dysfunction is a poorly understood condition that affects up to one-third of men around the world. Existing treatments that target the periphery do not work for all men. Previous studies have shown that central melanocortins, which are released by pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, can lead to male erection and increased libido. Several studies specifically implicate the melanocortin 4 receptor (MC4R) in the central control of sexual function, but the specific neural circuitry involved is unknown...
October 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/29057457/differential-effects-of-selective-agonists-of-neuromedin-u1-and-2-receptors-in-obese-and-diabetic-mice
#13
Hiroaki Nagai, Tomoko Kaisho, Kotaro Yokoyama, Tomoko Asakawa, Hisashi Fujita, Kouta Matsumiya, Jiro Noguchi, Kazue Tsuchimori, Naoki Nishizawa, Yoko Kanematsu-Yamaki, Katsuko Dote, Hiroshi Inooka, Jun-Ichi Sakamoto, Tetsuya Ohtaki, Taiji Asami, Shiro Takekawa
BACKGROUND AND PURPOSE: Neuromedin U (NMU) may be a novel target for obesity treatment owing to its anorectic and energy expenditure enhancing effects. Although two receptors, NMU1 and NMU2, are both responsible for the NMU-mediated anti-obesity effects, the receptor agonist with the most appropriate profiles for treating obesity and diabetes in terms of efficacy and safety is as yet unknown. Thus, we developed and evaluated novel NMU1/2 receptor-selective agonists. EXPERIMENTAL APPROACH: Efficacy and safety were assessed in mice with diet-induced obesity (DIO) and those with leptin-deficient diabetes (ob/ob) through repeated peripheral administration of selective agonists to NMU1 (NMU-6102) and NMU2 (NMU-2084), along with NMU1/2 non-selective agonists (NMU-0002 and NMU-6014)...
October 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29040444/re-establishment-of-energy-balance-in-a-male-mouse-model-with-pomc-neuron-deletion-of-bmpr1a
#14
Kristy L Townsend, Christopher Madden, Magdalena Blaszkiewicz, Lindsay McDougall, Domenico Tupone, Matthew D Lynes, Yuji Mishina, Paul Yu, Shaun Morrison, Yu-Hua Tseng
The regulation of energy balance involves complex processes in the brain, including coordination by hypothalamic neurons that contain pro-opiomelanocortin (POMC). We previously demonstrated that central bone morphogenetic protein 7 (BMP7) reduces appetite. Now we show that a type 1 BMP receptor, BMPR1A, is co-localized with POMC neurons and POMC-BMPR1A-KO mice are hyperphagic, revealing physiological involvement of BMP signaling in anorectic POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC-BMPR1A-KO mice exhibit a lack of obesity, even on a 45% high-fat diet...
October 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/29031731/evaluation-of-a-melanocortin-4-receptor-mc4r-agonist-setmelanotide-in-mc4r-deficiency
#15
Tinh-Hai Collet, Béatrice Dubern, Jacek Mokrosinski, Hillori Connors, Julia M Keogh, Edson Mendes de Oliveira, Elana Henning, Christine Poitou-Bernert, Jean-Michel Oppert, Patrick Tounian, Florence Marchelli, Rohia Alili, Johanne Le Beyec, Dominique Pépin, Jean-Marc Lacorte, Andrew Gottesdiener, Rebecca Bounds, Shubh Sharma, Cathy Folster, Bart Henderson, Stephen O'Rahilly, Elizabeth Stoner, Keith Gottesdiener, Brandon L Panaro, Roger D Cone, Karine Clément, I Sadaf Farooqi, Lex H T Van der Ploeg
OBJECTIVE: Pro-opiomelanocortin (POMC)-derived peptides act on neurons expressing the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a highly potent MC4R agonist that leads to weight loss in diet-induced obese animals and in obese individuals with complete POMC deficiency. While POMC deficiency is very rare, 1-5% of severely obese individuals harbor heterozygous mutations in MC4R. We sought to assess the efficacy of Setmelanotide in human MC4R deficiency. METHODS: We studied the effects of Setmelanotide on mutant MC4Rs in cells and the weight loss response to Setmelanotide administration in rodent studies and a human clinical trial...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031726/reduced-renal-sympathetic-nerve-activity-contributes-to-elevated-glycosuria-and-improved-glucose-tolerance-in-hypothalamus-specific-pomc-knockout-mice
#16
Kavaljit H Chhabra, Donald A Morgan, Benjamin P Tooke, Jessica M Adams, Kamal Rahmouni, Malcolm J Low
OBJECTIVE: Hypothalamic arcuate nucleus-specific pro-opiomelanocortin deficient (ArcPomc(-/-)) mice exhibit improved glucose tolerance despite massive obesity and insulin resistance. We demonstrated previously that their improved glucose tolerance is due to elevated glycosuria. However, the underlying mechanisms that link glucose reabsorption in the kidney with ArcPomc remain unclear. Given the function of the hypothalamic melanocortin system in controlling sympathetic outflow, we hypothesized that reduced renal sympathetic nerve activity (RSNA) in ArcPomc(-/-) mice could explain their elevated glycosuria and consequent enhanced glucose tolerance...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031712/mitochondrial-uncoupling-in-the-melanocortin-system-differentially-regulates-npy-and-pomc-neurons-to-promote-weight-loss
#17
Natalie Jane Michael, Stephanie Elise Simonds, Marco van den Top, Michael Alexander Cowley, David Spanswick
OBJECTIVE: The mitochondrial uncoupling agent 2,4-dinitrophenol (DNP), historically used as a treatment for obesity, is known to cross the blood-brain-barrier, but its effects on central neural circuits controlling body weight are largely unknown. As hypothalamic melanocortin neuropeptide Y/agouti-related protein (NPY/AgRP) and pro-opiomelanocortin (POMC) neurons represent key central regulators of food intake and energy expenditure we investigated the effects of DNP on these neurons, food intake and energy expenditure...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031711/lorcaserin-improves-glycemic-control-via-a-melanocortin-neurocircuit
#18
Luke K Burke, Emmanuel Ogunnowo-Bada, Teodora Georgescu, Claudia Cristiano, Pablo B Martinez de Morentin, Lourdes Valencia Torres, Giuseppe D'Agostino, Christine Riches, Nicholas Heeley, Yue Ruan, Marcelo Rubinstein, Malcolm J Low, Martin G Myers, Justin J Rochford, Mark L Evans, Lora K Heisler
OBJECTIVE: The increasing prevalence of type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating glucose homeostasis to accelerate the identification of new medications. Recent reports indicate that the obesity medication lorcaserin, a 5-hydroxytryptamine (5-HT, serotonin) 2C receptor (5-HT2CR) agonist, improves glycemic control in association with weight loss in obese patients with T2D. Here we evaluate whether lorcaserin has an effect on glycemia without body weight loss and how this effect is achieved...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29023418/association-between-stress-and-the-hpa-axis-in-the-atopic-dermatitis
#19
REVIEW
Tzu-Kai Lin, Lily Zhong, Juan Luis Santiago
The hypothalamic-pituitary-adrenal (HPA) axis is one of the body's neuroendocrine networks that responds to psychological stress (PS). In the skin, there exists a peripheral HPA axis similar to the central axis. Glucocorticoids (GCs) are key effector molecules of the HPA axis and are essential for cutaneous homeostasis. Atopic dermatitis (AD) is a condition typically characterized by a chronic relapsing course that often results in PS. HPA dysfunction is present in AD patients by the decreased response of GCs elevation to stress as compared to those unaffected by AD...
October 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28973533/the-prader-willi-syndrome-proteins-magel2-and-necdin-regulate-leptin-receptor-cell-surface-abundance-through-ubiquitination-pathways
#20
Tishani Methsala Wijesuriya, Leentje De Ceuninck, Delphine Masschaele, Matthea R Sanderson, Karin Vanessa Carias, Jan Tavernier, Rachel Wevrick
In Prader-Willi syndrome (PWS), obesity is caused by the disruption of appetite-controlling pathways in the brain. Two PWS candidate genes encode MAGEL2 and necdin, related melanoma antigen proteins that assemble into ubiquitination complexes. Mice lacking Magel2 are obese and lack leptin sensitivity in hypothalamic pro-opiomelanocortin neurons, suggesting dysregulation of leptin receptor (LepR) activity. Hypothalamus from Magel2-null mice had less LepR and altered levels of ubiquitin pathway proteins that regulate LepR processing (Rnf41, Usp8, and Stam1)...
November 1, 2017: Human Molecular Genetics
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