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Virginia Mela, Sara Jimenez, Alejandra Freire-Regatillo, Vicente Barrios, Eva-María Marco, Ana-Belén Lopez-Rodriguez, Jesús Argente, María-Paz Viveros, Julie A Chowen
The neonatal leptin surge, occurring from postnatal day (PND) 5 to 13 and peaking at PND9 in rodents, is important for the development of neuroendocrine circuits involved in metabolic control and reproductive function. We previously demonstrated that treatment with a leptin antagonist from PND 5 to 9, coincident with peak leptin levels in the neonatal surge, modified trophic factors and markers of cell turnover and neuronal maturation in the hypothalamus of peri-pubertal rats. The kisspeptin system and metabolic neuropeptide and hormone levels were also modified...
October 14, 2016: Peptides
Naiyan Chen, Hiroki Sugihara, Jinah Kim, Zhanyan Fu, Boaz Barak, Mriganka Sur, Guoping Feng, Weiping Han
Multiple hypothalamic neuronal populations that regulate energy balance have been identified. Although hypothalamic glia exist in abundance and form intimate structural connections with neurons, their roles in energy homeostasis are less known. Here we show that selective Ca(2+) activation of glia in the mouse arcuate nucleus (ARC) reversibly induces increased food intake while disruption of Ca(2+) signaling pathway in ARC glia reduces food intake. The specific activation of ARC glia enhances the activity of agouti-related protein/neuropeptide Y (AgRP/NPY)-expressing neurons but induces no net response in pro-opiomelanocortin (POMC)-expressing neurons...
October 18, 2016: ELife
S Pauliina Markkula, David Lyons, Chen-Yu Yueh, Christine Riches, Paul Hurst, Barbara Fielding, Lora K Heisler, Mark L Evans
Specialized metabolic-sensors in the hypothalamus regulate blood glucose levels by influencing hepatic glucose output and hypoglycemic counter regulatory responses. Hypothalamic reactive oxygen species (ROS) may act as a metabolic signal mediating responses to changes in glucose, other substrates and hormones. The role of ROS in the brain's control of glucose homeostasis remains unclear. We hypothesized that hydrogen peroxide (H2O2), a relatively stable form of ROS, acts as a sensor of neuronal glucose consumption and availability and that lowering brain H2O2 with the enzyme catalase would lead to systemic responses increasing blood glucose...
October 14, 2016: Endocrinology
Rafael Carvalho Torres, Nathalia Santos Magalhães, Patrícia M R E Silva, Marco A Martins, Vinicius F Carvalho
Increased hypothalamus-pituitary-adrenal axis (HPA) activity in diabetes is strongly associated with several morbidities noted in patients with the disease. We previously demonstrated that hyperactivity of HPA axis under diabetic conditions is associated with up-regulation of adrenocorticotrophic hormone (ACTH) receptors (MC2R) in adrenal and down-regulation of glucocorticoid receptors (GR and MR) in pituitary. This study investigates the role of peroxisome proliferator-activated receptor (PPAR)-γ in HPA axis hyperactivity in diabetic rats...
October 8, 2016: Experimental and Molecular Pathology
Dongyun Zhang, Marvin Bergsneider, Marilene B Wang, Anthony P Heaney
We recently demonstrated that the orphan nuclear receptor testicular receptor 4 (TR4) is a potent regulator of corticotroph tumor growth and hormone secretion. The Ras/Raf/MEK/ERK pathway is commonly overactivated in human tumors and we have demonstrated that corticotroph tumor TR4 is activated by ERK1/2-mediated phosphorylation. We evaluated effects of MEK-162, a selective, non-ATP-competitive allosteric inhibitor of MEK1/2, on murine and human in vitro and in vivo corticotroph tumor proliferation and adrenocorticotrophic hormone (ACTH) secretion...
September 30, 2016: Oncotarget
Lihua Yang, Jinmiao Zha, Zijian Wang
The present study investigated the effects on reproductive and interrenal system by pentachlorophenol (PCP) using in silico and in vivo assays. Molecular docking results indicated interacting potency of PCP with steroid receptors (ERα, ERβ, AR, GR) but not Cytochrome P450 enzymes (CYPs). In the in vivo assay, sexually matured rare minnow (Gobiocypris rarus) was exposed to environmental relevant concentrations of PCP (0, 0.5, 5, 50 μg L(-1)). In male fish, 14-d exposure caused up-regulation of mRNA levels of hepatic erα, erβ, ar, gr, vtg and gonadal erα, vtg, ar, dmrt1, providing evidence for agonistic activities for steroid receptors by PCP...
January 2017: Chemosphere
Matthew C Hale, Garrett J McKinney, Frank P Thrower, Krista M Nichols
Many migratory traits are heritable, but there is a paucity of evidence identifying the molecular mechanisms underlying differentiation in alternative migratory tactics, or in linking variation in gene expression to migratory behaviors. To that end, we examined differential gene expression in the brain transcriptome between young steelhead trout that had undergone the smoltification process, and resident rainbow trout (Oncorhynchus mykiss) from Sashin Creek, Alaska. Samples were sequenced from two time points: immediately before (at 20months of age) and during (2years of age) the presumed peak of smoltification...
September 4, 2016: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
Enrique Caso, Antonio Maestro, Cristina C Sabiers, Manuel Godino, Zaira Caracuel, Joana Pons, F Jesus Gonzalez, Rocio Bautista, M Gonzalo Claros, Jaime Caso-Onzain, Elena Viejo-Allende, Peter V Giannoudis, Sara Alvarez, Paolo Maietta, Enrique Guerado
Familial predisposition is among the major genetic risk factors for non-contact musculoskeletal tissue injuries. Personal genome sequence shows that different polymorphism profiles may account for the number and the degree of injuries and the recovery time. Genotyping studies allow investigation into genome factors with potential impact on pathogenesis of non-contact ligament injuries. We have studied a family with twin sibling males surgically diagnosed of an anterior cruciate ligament non-contact rupture and non-affected progenitors (father and mother) were subjected to whole exome sequencing (WES) analysis...
September 2016: Injury
Jia Sun, Yong Gao, Ting Yao, Yiru Huang, Zhenyan He, Xingxing Kong, Kai-Jiang Yu, Rui-Tao Wang, Hongbo Guo, Jianqun Yan, Yongsheng Chang, Hong Chen, Philipp E Scherer, Tiemin Liu, Kevin W Williams
OBJECTIVE: Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation - including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined...
October 2016: Molecular Metabolism
Kavaljit H Chhabra, Jessica M Adams, Graham L Jones, Miho Yamashita, Martin Schlapschy, Arne Skerra, Marcelo Rubinstein, Malcolm J Low
OBJECTIVE: A major challenge for obesity treatment is the maintenance of reduced body weight. Diet-induced obese mice are resistant to achieving normoweight once the obesogenic conditions are reversed, in part because lowered circulating leptin leads to a reduction in metabolic rate and a rebound of hyperphagia that defend the previously elevated body weight set point. Because hypothalamic POMC is a central leptin target, we investigated whether changes in circulating leptin modify Pomc expression to maintain normal energy balance in genetically predisposed obese mice...
October 2016: Molecular Metabolism
Maria Manfredi-Lozano, Juan Roa, Francisco Ruiz-Pino, Richard Piet, David Garcia-Galiano, Rafael Pineda, Aurora Zamora, Silvia Leon, Miguel A Sanchez-Garrido, Antonio Romero-Ruiz, Carlos Dieguez, Maria Jesus Vazquez, Allan E Herbison, Leonor Pinilla, Manuel Tena-Sempere
OBJECTIVE: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic) health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction...
October 2016: Molecular Metabolism
M Ibars, A Ardid-Ruiz, M Suárez, B Muguerza, C Bladé, G Aragonès
OBJECTIVE: Dietary obesity is usually linked with hypothalamic leptin resistance, in which the primary impact is an interference in the homeostatic control of body weight and appetite. Notably, proanthocyanidins (PACs), which are the most abundant phenolic compounds present in human diet, modulate adiposity and food intake. The aim of this study was to assess whether PACs could re-establish appropriate leptin signalling in both the hypothalamus and peripheral tissues. DESIGN: Male Wistar rats were fed either a standard chow diet (STD group, n=7) or a cafeteria diet (CD) for 13 weeks...
October 18, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Malcolm J Low
No abstract text is available yet for this article.
November 2016: Nature Reviews. Endocrinology
Charlotte Sefton, Erika Harno, Alison Davies, Helen Small, Tiffany-Jayne Allen, Jonathan R Wray, Catherine B Lawrence, Anthony P Coll, Anne White
Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognised to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone-induced obesity, and analysed corticosterone levels in the hypothalamus and expression of genes relevant to Gc action...
September 20, 2016: Endocrinology
Liu Shanshan, Zhang Cuizhen, Peng Gang
Vertebrate feeding behavior is regulated by neuropeptide Y (NPY), GALANIN and GMAP prepropeptide (GAL), agouti related neuropeptide (AGRP) and proopiomelanocortin (POMC) in the hypothalamus. However, there are few studies on the relationship between these neuropeptides and feeding in zebrafish larvae. In the present study, real-time quantitative PCR and in situ hybridization were applied to examine the expression levels of npy, galanin, agrp and pomca in the hypothalamus of zebrafish larvae after starvation and re-feeding...
September 20, 2016: Yi Chuan, Hereditas
Miranda D Johnson, Sebastien G Bouret, Ambrose A Dunn-Meynell, Christina Neuner Boyle, Thomas A Lutz, Barry E Levin
Selectively bred diet-induced obese (DIO) rats become obese on a high fat diet and are leptin resistant before becoming obese. As compared to diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (αMSH; from pro-opiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC, but not NPY/AgRP neurons...
September 14, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Yi Zhu, Yong Gao, Caroline Tao, Mengle Shao, Shangang Zhao, Wei Huang, Ting Yao, Joshua A Johnson, Tiemin Liu, Aaron M Cypess, Olga Gupta, William L Holland, Rana K Gupta, David C Spray, Herbert B Tanowitz, Lei Cao, Matthew D Lynes, Yu-Hua Tseng, Joel K Elmquist, Kevin W Williams, Hua V Lin, Philipp E Scherer
"Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels...
September 13, 2016: Cell Metabolism
Claudio Ferrante, Giustino Orlando, Lucia Recinella, Sheila Leone, Annalisa Chiavaroli, Chiara Di Nisio, Rugia Shohreh, Fabio Manippa, Adriana Ricciuti, Michele Vacca, Luigi Brunetti
Irisin, the soluble secreted form of fibronectin type III domain containing 5 (FNDC5)-cleaved product, is a recently identified adipo-myokine that has been indicated as a possible link between physical exercise and energetic homeostasis. The co-localization of irisin with neuropeptide Y in hypothalamic sections of paraventricular nucleus, which receives NPY/AgRP projections from the arcuate nucleus, suggests a possible role of irisin in the central regulation of energy balance. In this context, in the present work we studied the effects of intra-hypothalamic irisin (1μl, 50-200nmol/l) administration on feeding and orexigenic [agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A] and anorexigenic [cocaine and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC)] peptides in male Sprague-Dawley rats...
September 8, 2016: European Journal of Pharmacology
Jae Hoon Jeong, Young Jae Woo, Streamson Chua, Young-Hwan Jo
The cholinoceptive system in the hypothalamus, in particular in the arcuate nucleus (ARC), plays a role in regulating food intake. Neurons in the ARC contain multiple neuropeptides, amines, and neurotransmitters. To study molecular and neurochemical heterogeneity of ARC neurons, we combine single-cell qRT-PCR and single-cell whole transcriptome amplification methods to analyze expression patterns of our hand-picked 60 genes in individual neurons in the ARC. Immunohistochemical and single-cell qRT-PCR analyses show choline acetyltransferase (ChAT)-expressing neurons in the ARC...
2016: PloS One
Jose P Silva, Guerline Lambert, Derek van Booven, Claes Wahlestedt
BACKGROUND: Epidemiological and animal studies have reported that prenatal nicotine exposure (PNE) leads to obesity and type-2 diabetes in offspring. Central leptin-melanocortin signaling via hypothalamic arcuate proopiomelanocortin (POMC) neurons is crucial for the regulation of energy and glucose balance. Furthermore, hypothalamic POMC neurons were recently found to mediate the anorectic effects of nicotine through activation of acetylcholine receptors. Here, we hypothesized that PNE impairs leptin-melanocortinergic regulation of energy balance in first-generation offspring by altering expression of long non-coding RNAs (lncRNAs) putatively regulating development and/or function of hypothalamic POMC neurons...
2016: Genome Medicine
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