PI3K integrates the effects of insulin and leptin on large-conductance Ca2+-activated K+ channels in neuropeptide Y neurons of the hypothalamic arcuate nucleus

2010 ◽  
Vol 298 (2) ◽  
pp. E193-E201 ◽  
Author(s):  
Meng-Jie Yang ◽  
Fang Wang ◽  
Jiang-Hua Wang ◽  
Wen-Ning Wu ◽  
Zhuang-Li Hu ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Intracellular Signaling ◽  
Arcuate Nucleus ◽  
Bk Channels ◽  
Intrinsic Activity ◽  
Neuron Activity ◽  
Physiological Processes ◽  
Body Adiposity ◽  
Combined Control ◽  
Hypothalamic Arcuate Nucleus

The adipocyte-derived hormone leptin and the pancreatic β-cell-derived hormone insulin function as afferent signals to the hypothalamus in an endocrine feedback loop that regulates body adiposity. They act in hypothalamic centers to modulate the function of specific neuronal subtypes, such as neuropeptide Y (NPY) neurons, by modifying neuronal electrical activity. To investigate the intrinsic activity of these neurons and their responses to insulin and leptin, we used a combination of morphological features and immunocytochemical technique to identify the NPY neurons of hypothalamic arcuate nucleus (ARC) and record whole cell large-conductance Ca2+-activated potassium (BK) currents on them. We found that both of the hormones increase the peak amplitude of BK currents, shifting the steady-state activation curve to the left. The effect of both insulin and leptin can be prevented by pretreatment with inhibitors of tyrosine kinase and phosphatidylinositol 3-kinase (PI3K) but not MAPK. These data indicate that PI3K-mediated signals are the common regulators of BK channels by insulin and leptin and mediated the two hormones' identical activatory effects on ARC NPY neurons. The effect of insulin and leptin together was similar to that of insulin or leptin alone, and leptin or insulin pretreatment did not lead to insulin- or leptin-sensitizing effects, respectively. These intracellular signaling mechanisms may play key roles in regulating ARC NPY neuron activity and physiological processes such as the control of food intake and body weight, which are under the combined control of insulin and leptin.

Diet-derived nutrients mediate the inhibition of hypothalamic NPY neurons in the arcuate nucleus of mice during refeeding

2009 ◽  
Vol 297 (1) ◽  
pp. R100-R110 ◽  
Author(s):  
Csilla Becskei ◽  
Thomas A. Lutz ◽  
Thomas Riediger
Keyword(s):  
Neuropeptide Y ◽  
Arcuate Nucleus ◽  
Peptide Yy ◽  
Small Reduction ◽  
Hypothalamic Arcuate Nucleus ◽  
Ad Libitum ◽  
Fos Expression

Fasting activates orexigenic neuropeptide Y neurons in the hypothalamic arcuate nucleus (ARC) of mice, which is reversed by 2 h refeeding with standard chow. Here, we investigated the contribution of diet-derived macronutrients and anorectic hormones to the reversal of the fasting-induced ARC activation during 2 h refeeding. Refeeding of 12-h-fasted mice with a cellulose-based, noncaloric mash induced only a small reduction in c-Fos expression. Refeeding with diets, containing carbohydrates, protein, or fat alone reversed it similar to chow; however, this effect depended on the amount of intake. The fasting-induced ARC activation was unchanged by subcutaneously injected amylin, CCK (both 20 μg/kg), insulin (0.2 U/kg and 0.05 U/kg) or leptin (2.6 mg/kg). Insulin and leptin had no effect on c-Fos expression in neuropeptide Y or proopiomelanocortin-containing ARC neurons. Interestingly, CCK but not amylin reduced the ghrelin-induced c-Fos expression in the ARC in ad libitum-fed mice, suggesting that CCK may inhibit orexigenic ARC neurons when acting together with other feeding-related signals. We conclude that all three macronutrients and also non-nutritive, ingestion-dependent signals contribute to an inhibition of orexigenic ARC neurons after refeeding. Similar to the previously demonstrated inhibitory in vivo action of peptide YY, CCK may be a postprandial mediator of ARC inhibition.

scholarly journals Insulin suppresses ghrelin-induced calcium signaling in neuropeptide Y neurons of the hypothalamic arcuate nucleus

Aging ◽  
2011 ◽  
Vol 3 (11) ◽  
pp. 1092-1097 ◽  
Author(s):  
Yuko Maejima ◽  
Daisuke Kohno ◽  
Yusaku Iwasaki ◽  
Toshihiko Yada
Keyword(s):  
Neuropeptide Y ◽  
Calcium Signaling ◽  
Arcuate Nucleus ◽  
Hypothalamic Arcuate Nucleus

scholarly journals Leptin Suppresses Ghrelin-Induced Activation of Neuropeptide Y Neurons in the Arcuate Nucleus via Phosphatidylinositol 3-Kinase- and Phosphodiesterase 3-Mediated Pathway

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2251-2263 ◽  
Author(s):  
Daisuke Kohno ◽  
Masanori Nakata ◽  
Fumihiko Maekawa ◽  
Ken Fujiwara ◽  
Yuko Maejima ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Neuropeptide Y ◽  
Phospholipase C ◽  
Arcuate Nucleus ◽  
Neuron Activity ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Adult Rats ◽  
Phosphodiesterase 3 ◽  
Phosphatidylinositol 3

Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) play a central role in stimulation of feeding. They sense and integrate peripheral and central signals, including ghrelin and leptin. However, the mechanisms of interaction of these hormones in NPY neurons are largely unknown. This study explored the interaction and underlying signaling cross talk between ghrelin and leptin in NPY neurons. Cytosolic Ca2+ concentration ([Ca2+]i) in single neurons isolated from ARC of adult rats was measured by fura-2 microfluorometry. Ghrelin increased [Ca2+]i in 31% of ARC neurons. The [Ca2+]i increases were inhibited by blockers of phospholipase C, adenylate cyclase, and protein kinase A. Ghrelin-induced [Ca2+]i increases were suppressed by subsequent administration of leptin. Fifteen of 18 ghrelin-activated, leptin-suppressed neurons (83%) contained NPY. Leptin suppression of ghrelin responses was prevented by pretreatment with inhibitors of phosphatidylinositol 3-kinase and phosphodiesterase 3 (PDE3) but not MAPK. ATP-sensitive potassium channel inhibitors and activators did not prevent and mimic leptin suppression, respectively. Although leptin phosphorylated signal-transducer and activator of transcription 3 (STAT3) in NPY neurons, neither STAT3 inhibitor nor genetic STAT3 deletion altered leptin suppression of ghrelin responses. Furthermore, orexigenic effect of intracerebroventricular ghrelin in rats was counteracted by leptin in a PDE3-dependent manner. These findings indicate that ghrelin increases [Ca2+]i via mechanisms depending on phospholipase C and adenylate cyclase-PKA pathways in ARC NPY neurons and that leptin counteracts ghrelin responses via a phosphatidylinositol 3-kinase-PDE3 pathway. This interaction may play an important role in regulating ARC NPY neuron activity and, thereby, feeding.

scholarly journals Nicotine excites hypothalamic arcuate anorexigenic proopiomelanocortin neurons and orexigenic neuropeptide Y neurons: similarities and differences

2011 ◽  
Vol 106 (3) ◽  
pp. 1191-1202 ◽  
Author(s):  
Hao Huang ◽  
Youfen Xu ◽  
Anthony N. van den Pol
Keyword(s):  
Weight Loss ◽  
Neuropeptide Y ◽  
Arcuate Nucleus ◽  
Input Resistance ◽  
Cell Types ◽  
Underlying Mechanism ◽  
Synaptic Activity ◽  
Cognitive Arousal ◽  
Hypothalamic Arcuate Nucleus ◽  
Prevalence Of Obesity

Two of the biggest health problems facing us today are addiction to nicotine and the increased prevalence of obesity. Interestingly, nicotine attenuates obesity, but the underlying mechanism is not clear. Here we address the hypothesis that if weight-reducing actions of nicotine are mediated by anorexigenic proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus, nicotine should excite these cells. Nicotine at concentrations similar to those found in smokers, 100–1,000 nM, excited POMC cells by mechanisms based on increased spike frequency, depolarization of membrane potential, and opening of ion channels. This was mediated by activation of both α7 and α4β2 nicotinic receptors; by itself, this nicotine-mediated excitation could explain weight loss caused by nicotine. However, in control experiments nicotine also excited the orexigenic arcuate nucleus neuropeptide Y (NPY) cells. Nicotine exerted similar actions on POMC and NPY cells, with a slightly greater depolarizing action on POMC cells. Immunocytochemistry revealed cholinergic axons terminating on both cell types. Nicotine actions were direct in both cell types, with nicotine depolarizing the membrane potentials and reducing input resistance. We found no differences in the relative desensitization to nicotine between POMC and NPY neurons. Nicotine inhibited excitatory synaptic activity recorded in NPY, but not POMC, cells. Nicotine also excited hypocretin/orexin neurons that enhance cognitive arousal, but the responses were smaller than in NPY or POMC cells. Together, these results indicate that nicotine has a number of similar actions, but also a few different actions, on POMC and NPY neurons that could contribute to the weight loss associated with smoking.

Neuronal circuits involving neuropeptide Y in hypothalamic arcuate nucleus-mediated feeding regulation

Neuropeptides ◽  
2012 ◽  
Vol 46 (6) ◽  
pp. 285-289 ◽  
Author(s):  
Haruaki Kageyama ◽  
Fumiko Takenoya ◽  
Satoshi Hirako ◽  
Nobuhiro Wada ◽  
Yuri Kintaka ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Arcuate Nucleus ◽  
Neuronal Circuits ◽  
Feeding Regulation ◽  
Hypothalamic Arcuate Nucleus

scholarly journals Neural Basis for Regulation of Vasopressin Secretion by Anticipated Disturbances in Osmolality

2021 ◽  
Author(s):  
Angela Kim ◽  
Joseph C. Madara ◽  
Chen Wu ◽  
Mark L. Andermann ◽  
Bradford B. Lowell
Keyword(s):  
Water Balance ◽  
Arcuate Nucleus ◽  
Feedback Regulation ◽  
Neural Mechanisms ◽  
Neuron Activity ◽  
Neural Basis ◽  
Water Excretion ◽  
Hypothalamic Arcuate Nucleus ◽  
Vasopressin Secretion ◽  
Renal Water Excretion

AbstractWater balance, tracked by extracellular osmolality, is regulated by feedback and feedforward mechanisms. Feedback regulation is reactive, occurring as deviations in osmolality are detected. Feedforward or presystemic regulation is proactive, occurring when disturbances in osmolality are anticipated. Vasopressin (AVP) is a key hormone regulating water balance and is released during hyperosmolality to limit renal water excretion. AVP neurons are under feedback and feedforward regulation. Not only do they respond to disturbances in blood osmolality, but they are also rapidly suppressed and stimulated, respectively, by drinking and eating, which will ultimately decrease and increase osmolality. Here, we demonstrate that AVP neuron activity is regulated by multiple anatomically-and functionally-distinct neural circuits. Notably, presystemic regulation during drinking and eating are mediated by non-overlapping circuits that involve the lamina terminalis and hypothalamic arcuate nucleus, respectively. These findings reveal neural mechanisms that support differential regulation of AVP release by diverse behavioral and physiological stimuli.

scholarly journals A role for glial fibrillary acidic protein (GFAP)-expressing cells in the regulation of gonadotropin-releasing hormone (GnRH) but not arcuate kisspeptin neuron output

2021 ◽  
Author(s):  
Charlotte Vanacker ◽  
R. Anthony DeFazio ◽  
Charlene M. Sykes ◽  
Suzanne M. Moenter
Keyword(s):  
Arcuate Nucleus ◽  
Designer Drugs ◽  
Neuron Activity ◽  
Gnrh Neurons ◽  
Hypothalamic Arcuate Nucleus ◽  
Lh Release ◽  
Main Regulator ◽  
Kndy Neurons

AbstractGnRH neurons are the final central neural output regulating fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (KNDy neurons) are considered the main regulator of GnRH output. GnRH and KNDy neurons are surrounded by astrocytes, which can modulate neuronal activity and communicate over distances. Prostaglandin E2 (PGE2), synthesized primarily by astrocytes, increases GnRH neuron activity and downstream pituitary release of luteinizing hormone (LH). We hypothesized GFAP-expressing astrocytes play a role regulating GnRH and/or KNDy neuron activity and LH release. We used adenoassociated viruses to target designer receptor exclusively activated by designer drugs (DREADDs) to GFAP-expressing cells to activate Gq or Gi-mediated signaling. Activating Gq signaling in the preoptic area, near GnRH neurons, but not in the arcuate, increases LH release in vivo and GnRH firing in vitro via a mechanism in part dependent upon PGE2. These data suggest astrocytes can activate GnRH/LH release in a manner independent of KNDy neurons.

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