Effect of leptin administration versus re-feeding on hypothalamic neuropeptide gene expression in fasted male rats

2004 ◽  
Vol 82 (12) ◽  
pp. 1128-1134 ◽  
Author(s):  
Edward D McAlister ◽  
Dean A Van Vugt
Keyword(s):  
Gene Expression ◽  
Leptin Receptor ◽  
Primary Source ◽  
Male Rats ◽  
In Situ Hybridization Histochemistry ◽  
Reproductive Axis ◽  
Physiological Relevance ◽  
Long Form ◽  
Induced Changes

Adipocytes are the primary source of circulating leptin. Leptin inhibits eating, increases metabolism, and stimulates the reproductive axis. Numerous hypothalamic neuropeptides have been implicated in leptin's behavioral and neuroendocrine effects, including neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART). The aim of this study was to investigate the physiological relevance of leptin's signaling of nutritional status by comparing the effects of leptin with the effects of re-feeding on fasting-induced changes in the expression of the long form of the leptin receptor (Ob-Rb), NPY, and CART. Adult male rats were fasted for 48 h and treated with either intra cere broventricular (i.c.v.) or subcutaneous (s.c.) leptin throughout the fast, or fed ad libitum for 24 h after terminating the fast. Expression of NPY, Ob-Rb, and CART mRNA in the arcuate nucleus (ARC) was determined by in situ hybridization histochemistry and compared with vehicle-treated fed or fasted controls. Fasting increased NPY and Ob-Rb expression and decreased CART expression in the ARC. Leptin (regardless of route) and re-feeding were equally effective in normalizing CART mRNA expression. A similar trend was observed with Ob-Rb expression. In contrast, neither re-feeding nor s.c. leptin reversed the increased expression of NPY that was induced by fasting. Only i.c.v. leptin was effective in this regard. Our results indicate leptin and re-feeding are equally effective in normalizing fasting-induced changes in CART and Ob-Rb expression, but less effective in normalizing NPY expression. These results suggest that leptin is the primary nutritional signal regulating CART and Ob-Rb expression in the ARC, and highlight potential differences between CART and NPY neuron sensitivity to leptin signaling.Key words: CART, leptin receptor, NPY, neuropeptide gene expression, fasting, refeeding, hypothalamus.

Influence of photoperiod and gonadal status on food intake, adiposity, and gene expression of hypothalamic appetite regulators in a seasonal mammal

2007 ◽  
Vol 292 (1) ◽  
pp. R242-R252 ◽  
Author(s):  
Chantacha Anukulkitch ◽  
Alexandra Rao ◽  
Frank R. Dunshea ◽  
Dominique Blache ◽  
Gerald A. Lincoln ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Reproductive Axis ◽  
Pomc Gene ◽  
Gonadal Status ◽  
Long Photoperiod ◽  
Refractory Phase

We studied the effects of photoperiod on metabolic profiles, adiposity, and gene expression of hypothalamic appetite-regulating peptides in gonad-intact and castrated Soay rams. Groups of five to six animals were studied 6, 18, or 30 wk after switching from long photoperiod (LP: 16 h of light) to short photoperiod (SP: 8 h of light). Reproductive and metabolic indexes were measured in blood plasma. Expression of neuropeptide Y (NPY), proopiomelanocortin (POMC), and leptin receptor (ObRb) in the arcuate nucleus was measured using in situ hybridization. Testosterone levels of intact animals were low under LP, increased to a peak at 16 wk under SP, and then declined. Voluntary food intake (VFI) was high under LP in both intact and castrated animals, decreased to a nadir at 12–16 wk under SP, and then recovered, but only in intact rams as the reproductive axis became photorefractory to SP. NPY gene expression varied positively and POMC expression varied negatively with the cycle in VFI, with differences between intact and castrate rams in the refractory phase. ObRb expression decreased under SP, unrelated to changes in VFI. Visceral fat weight also varied between the intact and castrated animals across the cycle. We conclude that 1) photoperiodic changes in VFI reflect changes in NPY and POMC gene expression, 2) changes in ObRb gene expression are not necessarily determinants of changes in VFI, 3) gonadal status affects the pattern of VFI that changes with photoperiod, and 4) in the absence of gonadal factors, animals can eat less but gain adiposity.

scholarly journals Tanycyte-independent control of hypothalamic leptin signaling

2019 ◽  
Author(s):  
Sooyeon Yoo ◽  
David Cha ◽  
Dong Won Kim ◽  
Thanh V. Hoang ◽  
Seth Blackshaw
Keyword(s):  
Gene Expression ◽  
Single Molecule ◽  
Leptin Receptor ◽  
Cell Types ◽  
Leptin Signaling ◽  
And Function ◽  
Induced Changes ◽  
The Brain ◽  
Specific Deletion

AbstractLeptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for leptin receptor (LepR) expression is lacking, and the effect of tanycyte-specific deletion of LepR has not been investigated. In this study, we analyze the expression and function of the tanycytic LepR in mice. Using single-molecule fluorescent in situ hybridization (smfISH), RT-qPCR, single-cell RNA sequencing (scRNA-Seq), and selective deletion of the LepR in tanycytes, we are unable to detect expression of LepR in the tanycytes. Tanycyte-specific deletion of LepR likewise did not affect leptin-induced pSTAT3 expression in hypothalamic neurons, regardless of whether leptin was delivered by intraperitoneal or intracerebroventricular injection. Finally, we use activity-regulated scRNA-Seq (act-Seq) to comprehensively profile leptin-induced changes in gene expression in all cell types in mediobasal hypothalamus. Clear evidence for leptin signaling is only seen in endothelial cells and subsets of neurons, although virtually all cell types show leptin-induced changes in gene expression. We thus conclude that LepR expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling through a LepR-dependent mechanism, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms.

Isolation- and dehydration-induced changes in neuropeptide gene expression in the sheep hypothalamus

1993 ◽  
Vol 11 (2) ◽  
pp. 181-189 ◽  
Author(s):  
S G Matthews ◽  
R F Parrott ◽  
D J S Sirinathsinghji
Keyword(s):  
Gene Expression ◽  
Supraoptic Nucleus ◽  
Plasma Osmolality ◽  
Hybridization Histochemistry ◽  
In Situ Hybridization Histochemistry ◽  
Mrna Content ◽  
Powerful Stimulus ◽  
Stress Isolation ◽  
Induced Changes

ABSTRACT Changes in neuropeptide gene expression in the hypothalami of sheep subjected to psychological stress (isolation, 1 h; n=3) or dehydration (48 h; n=3) were examined using in-situ hybridization histochemistry. Compared with non-stressed euhydrated control animals (n=3), isolation induced significant accumulation of mRNA for corticotrophin-releasing hormone, pro-enkephalin and pro-dynorphin (DYN) in the paraventricular nucleus (PVN), but no change in mRNA content within the supraoptic nucleus (SON). By contrast, dehydration significantly increased DYN mRNA in the magnocellular neurones of the PVN and SON. However, neither isolation nor dehydration altered the expression of mRNA for vasopressin (AVP) in either the PVN or the SON. These results indicate that in the ovine hypothalamus (1) stress represents a powerful stimulus to co-ordinated neuropeptide synthesis and (2) expression of DYN mRNA and AVP mRNA may be independently regulated during changes in plasma osmolality.

scholarly journals Upregulation of Kiss-1 and Gpr54 Genes Expression in Pituitary of Male Rats Following the Central Administration of Neuropeptide Y

2019 ◽  
Vol 4 (4) ◽  
pp. 137-142
Author(s):  
Vahid Azizi ◽  
Shahrbanoo Oryan ◽  
Homayuon Khazali ◽  
Abdolkarim Hosseini
Keyword(s):  
Gene Expression ◽  
Pituitary Gland ◽  
Neuropeptide Y ◽  
Wistar Rats ◽  
Third Ventricle ◽  
Male Rats ◽  
Control Group ◽  
Central Administration ◽  
Reproductive Axis ◽  
Male Wistar Rats

Introduction: The neuropeptide Y (NPY) in the neural circuits of the hypothalamus has a stimulating effect on reproductive activities in mammals. Kisspeptin (KiSS1) is a quintessential neurotransmitter in the reproductive axis which directly stimulates gonadotropin-releasing hormone neurons in the hypothalamus. The distribution of KiSS1 expressing cells in the pituitary was described previously. Despite earlier reports showing the KiSS1 receptor, G-protein coupled receptor 54 (GPR54) expression in the pituitary, the potential physiological roles of kisspeptin at this gland have remained obscure. Accordingly, this study investigated the role of NPY on the relative expression of Kiss1 and Gpr54 genes in the pituitary gland in male Wistar rats. Methods: In general, 20 male Wistar rats weighing 200-250 g in 4 groups (5 in each group) received saline, NPY (2.3 nM), BIBP3226 (NPY receptor antagonist, 7.8 nM), and NPY+ BIBP3226. Then, they received the simultaneous injection of these molecules through the third ventricle of the brain. Finally, the relative mean expressions of Kiss1 and Gpr54 genes in the anterior pituitary were quantitatively analyzed by the real-time polymerase chain reaction. Results: The central injection of NPY increased the relative mean expressions of Kiss1 and Gpr54 genes in the pituitary gland compared to the control group although the injection of BIBP3226 eradicated these effects. However, the gene expression of Gpr54 in the rats receiving NPY coupled with BIBP3226 in hypophysis in comparison to the group receiving only NPY demonstrated a significant reduction (P<0.05). Conclusion: Overall, the central injection of NPY stimulated the gene expression of Kiss1 and Gpr54 in the pituitary gland.

Influence of IFN-γ on gene expression in normal human bronchial epithelial cells: modulation of IFN-γ effects by dexamethasone

2005 ◽  
Vol 23 (1) ◽  
pp. 28-45 ◽  
Author(s):  
Rafal Pawliczak ◽  
Carolea Logun ◽  
Patricia Madara ◽  
Jennifer Barb ◽  
Anthony F. Suffredini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Primary Source ◽  
Early Response ◽  
Normal Human Bronchial Epithelial ◽  
Bronchial Epithelial ◽  
Normal Human ◽  
Ifn Γ ◽  
Components Analysis ◽  
Induced Changes

Interferon gamma (IFN-γ) plays a role in a variety of lung inflammatory responses, and corticosteroids are frequently employed as a treatment in these conditions. Therefore, the effect of IFN-γ, of the corticosteroid dexamethasone (Dex), or of both on gene expression was studied in normal human bronchial epithelial (NHBE) cells. NHBE cells were exposed to medium alone, IFN-γ (300 U/ml), Dex (10−7 M), or both IFN-γ and Dex for 8 or 24 h. Gene expression was examined using oligonucleotide microarrays. A principal components analysis demonstrated that the IFN-γ treatment effect was the primary source of differences in the data. With a 5% false discovery rate, of the 66 genes upregulated by IFN-γ by twofold or greater at 8 h and 287 genes upregulated at 24 h, coincubation with Dex inhibited the expression of 2 genes at 8 h and 45 genes at 24 h. Prominent among these were cytokines and secreted proteins. Dex cotreatment increased expression of 65 of the 376 genes that were inhibited by IFN-γ by 50% at 24 h. The majority of these genes encode cell cycle or nuclear proteins. Dex alone increased the expression of only 22 genes and inhibited the expression of 7 genes compared with controls at 24 h. The effect of Dex on IFN-γ-induced changes suggests a specific, targeted effect on IFN-γ responses that is substantially greater than the effect of Dex alone. Dex had little effect on the immediate early response to IFN-γ but a significant effect on the late responses.

Ontogeny of the long form of leptin receptor gene expression in the porcine ovarian follicles

2013 ◽  
Vol 16 (1) ◽  
pp. 101-105
Author(s):  
N. Smolinska ◽  
T. Kaminski ◽  
G. Siawrys ◽  
J. Przala
Keyword(s):  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Follicular Development ◽  
Ovarian Follicles ◽  
Antral Follicles ◽  
Long Form ◽  
Rb Gene ◽  
Receptor Gene Expression

Abstract Leptin is a polypeptide hormone produced predominantly in adipocytes. It has been found to be implicated in the regulation of satiety and energy homeostasis. A role for leptin in reproduction was later suggested by findings that this hormone may be involved in the regulation of the hypothalamic- pituitary-gonadal axis via endocrine, paracrine and/or autocrine pathways. The objective of the study was to investigate the ontogeny of the long isoform of leptin receptor (OB-Rb) gene in porcine ovarian follicles. The expression of OB-Rb gene was detected in porcine primordial, primary, secondary and antral follicles by in situ hybridization. In summary, our data suggest that leptin might have a direct effect on porcine follicles and plays an important role in the follicular development.

Gene expression in the rat supraoptic nucleus induced by chronic hyperosmolality versus hyposmolality

2000 ◽  
Vol 279 (4) ◽  
pp. R1239-R1250 ◽  
Author(s):  
Eric Glasgow ◽  
Takashi Murase ◽  
Bingjun Zhang ◽  
Joseph G. Verbalis ◽  
Harold Gainer
Keyword(s):  
Gene Expression ◽  
Supraoptic Nucleus ◽  
Cdna Libraries ◽  
Global Changes ◽  
Cdna Clones ◽  
Mrna Levels ◽  
Magnocellular Neurons ◽  
In Situ Hybridization Histochemistry ◽  
Functional Classes

Magnocellular neurons of the hypothalamo-neurohypophysial system play a fundamental role in the maintenance of body homeostasis by secreting vasopressin and oxytocin in response to systemic osmotic perturbations. During chronic hyperosmolality, vasopressin and oxytocin mRNA levels increase twofold, whereas, during chronic hyposmolality, these mRNA levels decrease to 10–20% of that of normoosmolar control animals. To determine what other genes respond to these osmotic perturbations, we have analyzed gene expression during chronic hyper- versus hyponatremia. Thirty-seven cDNA clones were isolated by differentially screening cDNA libraries that were generated from supraoptic nucleus tissue punches from hyper- or hyponatremic rats. Further analysis of 12 of these cDNAs by in situ hybridization histochemistry confirmed that they are osmotically regulated. These cDNAs represent a variety of functional classes and include cytochrome oxidase, tubulin, Na+-K+-ATPase, spectrin, PEP-19, calmodulin, GTPase, DnaJ-like, clathrin-associated, synaptic glycoprotein, regulator of GTPase stimulation, and gene for oligodendrocyte lineage-myelin basic proteins. This analysis therefore suggests that adaptation to chronic osmotic stress results in global changes in gene expression in the magnocellular neurons of the supraoptic nucleus.

scholarly journals Caloric restriction reverses the deficits in leptin receptor protein and leptin signaling capacity associated with diet-induced obesity: role of leptin in the regulation of hypothalamic long-form leptin receptor expression

2004 ◽  
Vol 181 (2) ◽  
pp. 297-306 ◽  
Author(s):  
J Wilsey ◽  
PJ Scarpace
Keyword(s):  
Caloric Restriction ◽  
Leptin Receptor ◽  
Fold Increase ◽  
Receptor Expression ◽  
Male Rats ◽  
Receptor Protein ◽  
Leptin Signaling ◽  
Stat3 Phosphorylation ◽  
Long Form

The objectives of this study were to determine if reduced long-form leptin receptor (ObRb) expression in diet-induced obese (DIO) animals is associated with deficits in maximal leptin signaling and, secondly, to establish the effects of short-term caloric restriction (CR) on ObRb expression and function. Groups of DIO and life-long chow-fed (CHOW) F344xBN male rats, aged 6 months, were given an i.c.v. injection containing 2 micro g leptin or artificial cerebrospinal fluid (ACSF) vehicle. Leptin induced a >6-fold increase in STAT3 phosphorylation in CHOW rats, but less than 2-fold increase in DIO. Reduced maximal leptin-stimulated STAT3 phosphorylation in DIO rats was coupled with a decline in both ObRb expression and protein. At this point, subgroups of DIO and CHOW animals underwent CR for 30 days and were then tested for acute leptin responsiveness. CR resulted in a 45 and 85% increase respectively in leptin-stimulated STAT3 phosphorylation in CHOW and DIO animals. Similarly, CR increased ObRb expression and protein in both CHOW and DIO animals. To explore the role of leptin in regulating ObRb expression, we reversibly overexpressed leptin in the hypothalamus and found that ObRb mRNA inversely follows central leptin expression. By enhancing both ObRb expression and signaling capacity, CR may enhance leptin responsiveness in leptin-resistant DIO animals.

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