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opiomelanocortin

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https://www.readbyqxmd.com/read/29351427/role-of-ptp1b-in-pomc-neurons-during-chronic-high-fat-diet-sex-differences-in-regulation-of-liver-lipids-and-glucose-tolerance
#1
Nicola Aberdein, Robert J Dambrino, Jussara M do Carmo, Zhen Wang, Laura E Mitchell, Heather A Drummond, John E Hall
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin receptor signalling and may contribute to leptin resistance in diet-induced obesity. Although PTP1B inhibition has been suggested as a potential weight loss therapy, the role of specific neuronal PTP1B signalling in cardiovascular and metabolic regulation and the importance of sex differences in this regulation are still unclear. In this study, we investigated the impact of pro-opiomelanocortin (POMC) neuronal PTP1B deficiency in cardiometabolic regulation in male and female mice fed a high fat diet (HFD)...
December 20, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29343842/leptin-resistance-was-involved-in-susceptibility-to-overweight-in-the-striped-hamster-re-fed-with-high-fat-diet
#2
Ying Zhao, Li-Bing Chen, Si-Si Mao, Hong-Xia Min, Jing Cao
Food restriction (FR) is the most commonly used intervention to prevent the overweight. However, the lost weight is usually followed by "compensatory growth" when FR ends, resulting in overweight. The present study was aimed to examining the behavior patterns and hormones mechanisms underpinning the over-weight. Energy budget and body fat content, and several endocrine markers related to leptin signals were examined in the striped hamsters under 20% FR refed by either low-fat diet (LF group) or high-fat diet (HF group)...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316344/widespread-dynamic-and-pleiotropic-expression-of-the-melanocortin-1-receptor-mc1r-system-is-conserved-across-chick-mouse-and-human-embryonic-development
#3
Anna C Thomas, Pauline Heux, Chloe Santos, Wisenave Arulvasan, Nita Solanky, Magalie E Carey, Dianne Gerrelli, Veronica A Kinsler, Heather C Etchevers
BACKGROUND: MC1R, a G-protein coupled receptor with high affinity for alpha-melanocyte stimulating hormone (αMSH), modulates pigment production in melanocytes from many species and is associated with human melanoma risk. MC1R mutations affecting human skin and hair color also have pleiotropic effects on the immune response and analgesia. Variants affecting human pigmentation in utero alter the congenital phenotype of both oculocutaneous albinism and congenital melanocytic naevi, and have a possible effect on birthweight...
January 8, 2018: Birth Defects Research
https://www.readbyqxmd.com/read/29226825/desacetyl-%C3%AE-melanocyte-stimulating-hormone-and-%C3%AE-melanocyte-stimulating-hormone-are-required-to-regulate-energy-balance
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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