scholarly journals Nutritional Influences on Reproductive Neuroendocrine Output: Insulin, Leptin, and Orexigenic Neuropeptide Signaling in the Ovine Hypothalamus

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5313-5322 ◽  
Author(s):  
David W. Miller ◽  
Joanne L. Harrison ◽  
Ellen J. Bennett ◽  
Patricia A. Findlay ◽  
Clare L. Adam
Keyword(s):  
Gene Expression ◽  
Neuropeptide Y ◽  
Leptin Receptor ◽  
Nutritional Influences ◽  
Hypothalamic Arcuate Nucleus ◽  
Melanocortin Signaling ◽  
Neuroendocrine Responses ◽  
Peptide Gene ◽  
Plasma Leptin ◽  
The Brain

This study investigated how changing nutritional status may alter reproductive neuroendocrine (LH) output via circulating leptin and insulin signaling through orexigenic hypothalamic pathways. Thin sheep were given an increasing nutritional plane (INP), sheep with intermediate adiposity a static nutritional plane (SNP), and fat sheep a decreasing nutritional plane (DNP) for 6 wk. Mean group adiposities converged by wk 6, LH output increased in INP, remained unchanged in SNP, and decreased in DNP sheep. Plasma and cerebrospinal fluid (CSF) insulin and plasma leptin concentrations increased in INP but did not change in the SNP and DNP groups. In INP sheep, LH output correlated positively with adiposity and plasma and CSF insulin concentrations and negatively with orexigenic neuropeptide Y gene expression in the hypothalamic arcuate nucleus (ARC). In DNP sheep, LH output correlated positively with adiposity, CSF leptin concentrations, and ARC proopiomelanocortin gene expression and negatively with leptin receptor (OB-Rb) and agouti-related peptide gene expression in the ARC. These data are consistent with the feedback response to an increasing nutritional plane being mediated by increasing circulating insulin entering the brain and stimulating LH via inhibition of hypothalamic neuropeptide Y and the response to a decreasing nutritional plane being mediated by altered hypothalamic leptin signaling brought about by increased OB-Rb expression and decreased melanocortin signaling. Because end point adiposity was similar yet LH output was different, the hypothalamus apparently retains a nutritional memory, based on changes in orexigenic neuropeptide expression, that influences contemporary neuroendocrine responses.

scholarly journals The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure

2007 ◽  
Vol 193 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Hiroyuki Shimizu ◽  
Kinji Inoue ◽  
Masatomo Mori
Keyword(s):  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Signaling System ◽  
Leptin Signaling ◽  
Melanocyte Stimulating Hormone ◽  
Hypothalamic Nuclei ◽  
Hypothalamic Arcuate Nucleus ◽  
Melanocortin Signaling ◽  
The Brain

The brain hypothalamus coordinates extra-hypothalamic regions to maintain energy homeostasis through the regulation of food intake and energy expenditure. A number of anorexigenic and orexigenic molecules in the hypothalamic nuclei participate in the control of energy homeostasis. Leptin and pro-opiomelanocortin (POMC)-derived α-melanocyte-stimulating hormone are key anorectic molecules, and the leptin receptor and POMC gene are both expressed in the hypothalamic arcuate nucleus. Although it has been considered that melanocortin signaling is localized downstream to leptin signaling, data have accumulated to support the concept of a leptin-independent melanocortin signaling system. We focus on and review the melanocortin signaling system that functions dependently or independently of leptin signaling in the regulation of energy homeostasis.

Photoperiod regulates arcuate nucleus POMC, AGRP, and leptin receptor mRNA in Siberian hamster hypothalamus

2000 ◽  
Vol 278 (1) ◽  
pp. R271-R281 ◽  
Author(s):  
Julian G. Mercer ◽  
Kim M. Moar ◽  
Alexander W. Ross ◽  
Nigel Hoggard ◽  
Peter J. Morgan
Keyword(s):  
Gene Expression ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Separate Experiment ◽  
Siberian Hamsters ◽  
Hypothalamic Arcuate Nucleus ◽  
Melanin Concentrating Hormone ◽  
Specific Regulation ◽  
Plasma Leptin ◽  
Agouti Related Protein

Siberian hamsters decreased body weight by 30% during 18 wk in short day (SD) vs. long day (LD) controls. Subsequent imposed food deprivation (FD; 24 h) caused a further 10% decrease. In the hypothalamic arcuate nucleus (ARC), SDs reduced proopiomelanocortin (POMC) gene expression and agouti-related protein (AGRP) mRNA was elevated, changes that summate to reduced catabolic drive through the melanocortin receptors. There was no effect of photoperiod on neuropeptide Y (NPY), melanin concentrating hormone, orexin, or corticotropin-releasing factor mRNAs. Superimposed FD increased AGRP gene expression and caused a localized elevation of NPY mRNA in the ARC. Both adipose tissue leptin and ARC leptin receptor (OB-Rb) mRNAs were downregulated in SDs, whereas FD increased OB-Rb gene expression. Thus OB-Rb mRNA is differentially regulated by acute and chronic changes in plasma leptin in this species. In a separate experiment in LDs, AGRP gene expression was increased by 24 or 48 h FD, whereas POMC mRNA was downregulated in the caudal ARC. AGRP and NPY mRNAs were extensively coexpressed in the ARC, and their differential regulation by photoperiod and FD is suggestive of transcript-specific regulation at the level of individual neurons.

Leptin secretion and hypothalamic neuropeptide and receptor gene expression in sheep

2002 ◽  
Vol 282 (4) ◽  
pp. R1227-R1235 ◽  
Author(s):  
Annette Sorensen ◽  
Clare L. Adam ◽  
Pat A. Findlay ◽  
Michel Marie ◽  
Louise Thomas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Negative Energy ◽  
Receptor Expression ◽  
Melanocortin Receptor ◽  
Hypothalamic Nucleus ◽  
Hypothalamic Arcuate Nucleus ◽  
Ad Libitum ◽  
Peptide Gene ◽  
Plasma Leptin

Peripheral and hypothalamic mechanisms underlying the hyperphagia of lactation have been investigated in sheep. Sheep were fed ad libitum and killed at 6 and 18 days of lactation; ad libitum-fed nonlactating sheep were killed as controls. Despite increased food intake, lactating ewes were in negative energy balance. Lactation decreased plasma leptin and adipose tissue leptin mRNA concentrations. OB-Rb gene expression, determined by in situ hybridization, was increased in the hypothalamic arcuate nucleus (ARC) and ventromedial hypothalamic nucleus (VMH) at both stages of lactation. Neuropeptide Y (NPY) was increased by lactation in both the ARC and dorsomedial hypothalamus (DMH), although increased gene expression in the DMH was only apparent at day 18 of lactation. Gene expression was decreased for cocaine- and amphetamine-regulated transcript (CART) in the ARC and VMH and for proopiomelanocortin in ARC during lactation. Agouti-related peptide gene expression was increased in the ARC, and melanocortin receptor expression was unchanged in both the ARC and VMH with lactation. Thus the hypoleptinemia of lactation may activate NPY orexigenic pathways and attenuate anorexigenic melanocortin and CART pathways in the hypothalamus to promote the hyperphagia of lactation.

Lateral ventricular ghrelin and fourth ventricular ghrelin induce similar increases in food intake and patterns of hypothalamic gene expression

2006 ◽  
Vol 290 (6) ◽  
pp. R1565-R1569 ◽  
Author(s):  
Kimberly P. Kinzig ◽  
Karen A. Scott ◽  
Jayson Hyun ◽  
Sheng Bi ◽  
Timothy H. Moran
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Time Course ◽  
Arcuate Nucleus ◽  
Central Administration ◽  
Stimulatory Action ◽  
Hypothalamic Arcuate Nucleus ◽  
Ghrelin Receptors ◽  
The Brain

The gut peptide ghrelin has been shown to stimulate food intake after both peripheral and central administration, and the hypothalamic arcuate nucleus has been proposed to be the major site for mediating this feeding stimulatory action. Ghrelin receptors are widely distributed in the brain, and hindbrain ghrelin administration has been shown to potently stimulate feeding, suggesting that there may be other sites for ghrelin action. In the present study, we have further assessed potential sites for ghrelin action by comparing the ability of lateral and fourth ventricular ghrelin administration to stimulate food intake and alter patterns of hypothalamic gene expression. Ghrelin (0.32, 1, or 3.2 nmol) in the lateral or fourth ventricle significantly increased food intake in the first 4 h after injection, with no ventricle-dependent differences in degree or time course of hyperphagia. One nanomole of ghrelin into either the lateral or fourth ventricle resulted in similar increases in arcuate nucleus neuropeptide Y mRNA expression. Expression levels of agouti-related peptide or proopiomelanocortin mRNA were not affected by ghrelin administration. These data demonstrate that ghrelin can affect food intake and hypothalamic gene expression through interactions at multiple brain sites.

Rapid change of neuropeptide Y levels and gene-expression in the brain of ovariectomized mice after administration of 17β-estradiol

Neuropeptides ◽  
2009 ◽  
Vol 43 (4) ◽  
pp. 327-332 ◽  
Author(s):  
Susanne Hilke ◽  
Lovisa Holm ◽  
Katarina Åman ◽  
Tomas Hökfelt ◽  
Elvar Theodorsson
Keyword(s):  
Gene Expression ◽  
Neuropeptide Y ◽  
Rapid Change ◽  
Ovariectomized Mice ◽  
17Β Estradiol ◽  
The Brain

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.

Parasite-induced anorexia: leptin, insulin and corticosterone responses to infection with the nematode, Nippostrongylus brasiliensis

Parasitology ◽  
1999 ◽  
Vol 118 (1) ◽  
pp. 117-123 ◽  
Author(s):  
H. C. ROBERTS ◽  
L. J. HARDIE ◽  
L. H. CHAPPELL ◽  
J. G. MERCER
Keyword(s):  
Gene Expression ◽  
Energy Balance ◽  
Neuropeptide Y ◽  
Post Infection ◽  
Plasma Insulin ◽  
Negative Energy ◽  
Nippostrongylus Brasiliensis ◽  
Corticotrophin Releasing Factor ◽  
Ad Libitum ◽  
Plasma Leptin

The nematode parasite, Nippostrongylus brasiliensis, induces a biphasic anorexia in its rat host. The mechanisms, underlying this anorexia and its possible advantages to the host or parasite are unknown. We have investigated the effect of acute (12–24 h) and chronic (2–17 days) infections on plasma concentrations of leptin, insulin and corticosterone, and on hypothalamic expression of neuropeptide Y, galanin and corticotrophin-releasing factor genes. Plasma leptin was elevated in infected rats relative to uninfected ad libitum-fed controls and pair-fed controls in 12 h infections initiated at dark onset and in infections of 2 days' duration. At other times prior to parasite expulsion, plasma leptin in infected and pair-fed rats was lower than that of uninfected ad libitum-fed controls, reflecting the existing state of negative energy balance. Elevated plasma leptin concentrations in infected rats at day 2 post-infection were accompanied by reduced neuropeptide Y gene expression in the hypothalamic arcuate nucleus compared with both ad libitum control and pair-fed animals, and by lowered corticotrophin-releasing factor gene expression in the paraventricular nucleus relative to pair-feds. Twelve hour infections were characterized by a substantial increase in plasma corticosterone that was independent of reduced food intake, and in 12 h infections initiated at dark onset, where plasma leptin was elevated, there was also increased plasma insulin concentration in infected rats. In longer infections, differences between the groups in plasma insulin and corticosterone concentration were only observed at day 4 post-infection. In summary, perturbations to leptin, insulin and corticosterone signals early in infection may have a causative role and might feed back onto hypothalamic gene expression, whereas subsequent changes in these parameters are more likely to be secondary to negative energy balance.

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