scholarly journals Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Jian Qiu ◽  
Heidi M Rivera ◽  
Martha A Bosch ◽  
Stephanie L Padilla ◽  
Todd L Stincic ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Arcuate Nucleus ◽  
Neuronal Excitability ◽  
Glutamate Release ◽  
Metabotropic Receptors ◽  
Hypothalamic Arcuate Nucleus ◽  
17Β Estradiol ◽  
Arcuate Neurons ◽  
Feeding Circuits

The neuropeptides tachykinin2 (Tac2) and kisspeptin (Kiss1) in hypothalamic arcuate nucleus Kiss1 (Kiss1ARH) neurons are essential for pulsatile release of GnRH and reproduction. Since 17β-estradiol (E2) decreases Kiss1 and Tac2 mRNA expression in Kiss1ARH neurons, the role of Kiss1ARH neurons during E2-driven anorexigenic states and their coordination of POMC and NPY/AgRP feeding circuits have been largely ignored. Presently, we show that E2 augmented the excitability of Kiss1ARH neurons by amplifying Cacna1g, Hcn1 and Hcn2 mRNA expression and T-type calcium and h-currents. E2 increased Slc17a6 mRNA expression and glutamatergic synaptic input to arcuate neurons, which excited POMC and inhibited NPY/AgRP neurons via metabotropic receptors. Deleting Slc17a6 in Kiss1 neurons eliminated glutamate release and led to conditioned place preference for sucrose in E2-treated KO female mice. Therefore, the E2-driven increase in Kiss1 neuronal excitability and glutamate neurotransmission may play a key role in governing the motivational drive for palatable food in females.

scholarly journals Changes in mRNA expression of arcuate nucleus appetite-regulating peptides during lactation in rats

2013 ◽  
Vol 52 (2) ◽  
pp. 97-109 ◽  
Author(s):  
Yoshihiro Suzuki ◽  
Keiko Nakahara ◽  
Keisuke Maruyama ◽  
Rieko Okame ◽  
Takuya Ensho ◽  
...  
Keyword(s):  
Food Intake ◽  
Mrna Expression ◽  
Arcuate Nucleus ◽  
Peptide Yy ◽  
Weaning Food ◽  
Hypothalamic Arcuate Nucleus ◽  
Pregnancy And Lactation ◽  
Acyl Ghrelin ◽  
Plasma Leptin ◽  
Agouti Related Protein

The contribution of hypothalamic appetite-regulating peptides to further hyperphagia accompanying the course of lactation in rats was investigated by using PCR array and real-time PCR. Furthermore, changes in the mRNA expression for appetite-regulating peptides in the hypothalamic arcuate nucleus (ARC) were analyzed at all stages of pregnancy and lactation, and also after weaning. Food intake was significantly higher during pregnancy, lactation, and after weaning than during non-lactation periods. During lactation, ARC expression of mRNAs for agouti-related protein (AgRP) and peptide YY was increased, whereas that of mRNAs for proopiomelanocortin (POMC) and cholecystokinin (CCK) was decreased, in comparison with non-lactation periods. The increase in AgRP mRNA expression during lactation was especially marked. The plasma level of leptin was significantly decreased during the course of lactation, whereas that of acyl-ghrelin was unchanged. In addition, food intake was negatively correlated with the plasma leptin level during lactation. This study has clarified synchronous changes in the expression of many appetite-regulating peptides in ARC of rats during lactation. Our results suggest that hyperphagia during lactation in rats is caused by decreases in POMC and CCK expression and increases in AgRP expression in ARC, the latter being most notable. Together with the decrease in the blood leptin level, such changes in mRNA expression may explain the further hyperphagia accompanying the course of lactation.

scholarly journals PrPC as a Transducer of Physiological and Pathological Signals

2021 ◽  
Vol 14 ◽  
Author(s):  
Jessica D. Panes ◽  
Paulina Saavedra ◽  
Benjamin Pineda ◽  
Kathleen Escobar ◽  
Magdalena E. Cuevas ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Physiological Role ◽  
Cellular Prion Protein ◽  
Amyloid Peptide ◽  
Metabotropic Receptors ◽  
Cellular Analysis ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Β Amyloid Peptide

After the discovery of prion phenomenon, the physiological role of the cellular prion protein (PrPC) remained elusive. In the past decades, molecular and cellular analysis has shed some light regarding interactions and functions of PrPC in health and disease. PrPC, which is located mainly at the plasma membrane of neuronal cells attached by a glycosylphosphatidylinositol (GPI) anchor, can act as a receptor or transducer from external signaling. Although the precise role of PrPC remains elusive, a variety of functions have been proposed for this protein, namely, neuronal excitability and viability. Although many issues must be solved to clearly define the role of PrPC, its connection to the central nervous system (CNS) and to several misfolding-associated diseases makes PrPC an interesting pharmacological target. In a physiological context, several reports have proposed that PrPC modulates synaptic transmission, interacting with various proteins, namely, ion pumps, channels, and metabotropic receptors. PrPC has also been implicated in the pathophysiological cell signaling induced by β-amyloid peptide that leads to synaptic dysfunction in the context of Alzheimer’s disease (AD), as a mediator of Aβ-induced cell toxicity. Additionally, it has been implicated in other proteinopathies as well. In this review, we aimed to analyze the role of PrPC as a transducer of physiological and pathological signaling.

scholarly journals Hypothyroidism Compromises Hypothalamic Leptin Signaling in Mice

2013 ◽  
Vol 27 (4) ◽  
pp. 586-597 ◽  
Author(s):  
Claudia Groba ◽  
Steffen Mayerl ◽  
Alies A. van Mullem ◽  
Theo J. Visser ◽  
Veerle M. Darras ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Double Knockout ◽  
Hypothalamic Arcuate Nucleus ◽  
The Central Nervous System ◽  
Leptin Expression ◽  
The Impact

Abstract The impact of thyroid hormone (TH) on metabolism and energy expenditure is well established, but the role of TH in regulating nutritional sensing, particularly in the central nervous system, is only poorly defined. Here, we studied the consequences of hypothyroidism on leptin production as well as leptin sensing in congenital hypothyroid TRH receptor 1 knockout (Trhr1 ko) mice and euthyroid control animals. Hypothyroid mice exhibited decreased circulating leptin levels due to a decrease in fat mass and reduced leptin expression in white adipose tissue. In neurons of the hypothalamic arcuate nucleus, hypothyroid mice showed increased leptin receptor Ob-R expression and decreased suppressor of cytokine signaling 3 transcript levels. In order to monitor putative changes in central leptin sensing, we generated hypothyroid and leptin-deficient animals by crossing hypothyroid Trhr1 ko mice with the leptin-deficient ob/ob mice. Hypothyroid Trhr1/ob double knockout mice showed a blunted response to leptin treatment with respect to body weight and food intake and exhibited a decreased activation of phospho-signal transducer and activator of transcription 3 as well as a up-regulation of suppressor of cytokine signaling 3 upon leptin treatment, particularly in the arcuate nucleus. These data indicate alterations in the intracellular processing of the leptin signal under hypothyroid conditions and thereby unravel a novel mode of action by which TH affects energy metabolism.

scholarly journals Testosterone or 17β-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes

2011 ◽  
Vol 210 (2) ◽  
pp. 219-229 ◽  
Author(s):  
Firoozeh Salehzadeh ◽  
Anna Rune ◽  
Megan Osler ◽  
Lubna Al-Khalili
Keyword(s):  
Lipid Metabolism ◽  
Mrna Expression ◽  
Sex Hormone ◽  
Dependent Manner ◽  
Testosterone Treatment ◽  
Palmitate Oxidation ◽  
Glucose And Lipid Metabolism ◽  
Human Myotubes ◽  
17Β Estradiol

Changes in sex hormone levels with aging or illness may lead to metabolic disorders. Moreover, the ratio changes in men versus women may have distinct pathological responses. Since little is known about sex hormone action on muscle metabolism, we examined the role of testosterone or 17β-estradiol (E2) in metabolism and investigated whether either hormone may mediate a sex-specific effect. Myotubes from postmenopausal women and age-matched male donors were treated with 10 nM testosterone or E2 for 4 days, and assays were performed to measure metabolic readouts, signal transduction, and mRNA expression. Testosterone and E2 treatment enhanced insulin-stimulated glucose incorporation into glycogen and AKT phosphorylation in myotubes from female donors, highlighting a sex-specific role of sex hormone in glucose metabolism. Testosterone treatment increased palmitate oxidation in myotubes from both female and male donors, while E2 enhanced palmitate oxidation in myotubes from male donors only. Testosterone-mediated increase in palmitate oxidation was attenuated at the presence of androgen receptor antagonist, which may indicate a role of nuclear steroid receptor in muscle lipid oxidation. Testosterone treatment increased mRNA expression of the insulin receptor substrate 2 in myotubes from male and female donors, whereas it increased mRNA expression of glycogen synthase 1 only in myotubes from male donors. E2 treatment increased pyruvate dehydrogenase kinase 4 mRNA expression in myotubes from female donors. Thus, our data suggest that testosterone or E2 modulates muscle glucose and lipid metabolism and may play a role in metabolism in a sex-dependent manner.

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