scholarly journals Effect of peripheral administration of cholecystokinin on food intake in apolipoprotein AIV knockout mice

2012 ◽  
Vol 302 (11) ◽  
pp. G1336-G1342 ◽  
Author(s):  
Go Yoshimichi ◽  
Chunmin C. Lo ◽  
Kellie L. K. Tamashiro ◽  
Liyun Ma ◽  
Dana M. Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Food System ◽  
Nucleus Tractus Solitarius ◽  
Wild Type ◽  
Post Hoc Analysis ◽  
Nodose Ganglia ◽  
Post Hoc ◽  
The Brain

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In this study, we determined whether CCK-8 (1, 3, or 5 μg/kg ip) reduces food intake in fasted apo AIV knockout (KO) mice as effectively as in fasted wild-type (WT) mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice had significantly reduced 30-min food intake following all doses of CCK-8, whereas WT mice had reduced food intake only at doses of 3 μg/kg and above. Post hoc analysis revealed that the reduction of 10-min and 30-min food intake elicited by each dose of CCK-8 was significantly larger in the apo AIV KO mice than in the WT mice. Peripheral CCK 1 receptor (CCK1R) gene expression (mRNA) in the duodenum and gallbladder of the fasted apo AIV KO mice was comparable to that in WT mice. In contrast, CCK1R mRNA in nodose ganglia of the apo AIV KO mice was upregulated relative to WT animals. Similarly, upregulated CCK1R gene expression was found in the brain stem of apo AIV KO mice by in situ hybridization. Although it is possible that the increased satiating potency of CCK in apo AIV KO mice is mediated by upregulation of CCK 1R in the nodose ganglia and nucleus tractus solitarius, additional experiments are required to confirm such a mechanism.

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.

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 The microRNA miR-18a Links Proliferation and Inflammation During Photoreceptor Regeneration in the Injured Zebrafish Retina

2021 ◽  
Author(s):  
Evin Magner ◽  
Pamela Sandoval-Sanchez ◽  
Peter F Hitchcock ◽  
Scott M Taylor
Keyword(s):  
Muller Glia ◽  
Müller Glia ◽  
Wild Type ◽  
Post Injury ◽  
Photoreceptor Layer ◽  
Brdu Labeling ◽  
Key Aspects ◽  
The Brain ◽  
Embryonic Retina

Abstract In mammals, photoreceptor loss causes permanent blindness, but in zebrafish (Danio rerio), Müller glia function as intrinsic stem cells, producing progenitor cells that regenerate photoreceptors and restore vision. MicroRNAs (miRNAs) critically regulate neurogenesis in the brain and retina, but the roles of miRNAs in injury-induced neuronal regeneration are largely unknown. The miRNA miR-18a regulates photoreceptor differentiation in the embryonic retina. The purpose of the current study was to determine the function of miR-18a during injury-induced photoreceptor regeneration. RT-qPCR, in-situ hybridization (ISH) and immunohistochemistry (IHC) showed that miR-18a expression increases throughout the retina by 1-day post-injury (dpi) and continues to increase through 5 dpi. Bromodeoxyuridine (BrdU) labeling showed that at 7 and 10 dpi, when regenerated photoreceptors are normally differentiating, there are more proliferating Müller glia-derived progenitors in homozygous miR-18a mutant (miR-18ami5012) retinas compared with wild type (WT), indicating that miR-18a negatively regulates injury-induced proliferation. At 7 and 10 dpi, miR-18ami5012 retinas have fewer mature photoreceptors than WT, but there is no difference at 14 dpi, revealing that photoreceptor regeneration is delayed. BrdU labeling showed that the excess progenitors in miR-18ami5012 retinas migrate to other retinal layers besides the photoreceptor layer. Inflammation is critical for photoreceptor regeneration and RT-qPCR showed that, in the absence of miR-18a, inflammation is prolonged. Suppressing inflammation with dexamethasone rescues the miR-18ami5012 phenotype. Together, these data show that during injury-induced photoreceptor regeneration, miR-18a regulates proliferation and photoreceptor regeneration by regulating key aspects of the inflammatory response during photoreceptor regeneration in zebrafish.

scholarly journals Imaging Sterols and Oxysterols in Mouse Brain Reveals Distinct Spatial Cholesterol Metabolism

2018 ◽  
Author(s):  
Eylan Yutuc ◽  
Roberto Angelini ◽  
Mark Baumert ◽  
Natalia Mast ◽  
Irina Pikuleva ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mouse Brain ◽  
Brain Function ◽  
Mass Spectrometry Imaging ◽  
Cholesterol Metabolism ◽  
Biologically Active ◽  
Wild Type ◽  
Tissue Slices ◽  
The Brain

AbstractDysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatisation in combination with micro-liquid-extraction for surface analysis and liquid chromatography - mass spectrometry to image sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400 µm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low abundance and difficult to ionise sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild type and cholesterol 24S-hydroxylase knock-out mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.SignificanceThe brain is a remarkably complex organ and cholesterol homeostasis underpins brain function. It is known that cholesterol is not evenly distributed across different brain regions, however, the precise map of cholesterol metabolism in the brain remains unclear. If cholesterol metabolism is to be correlated with brain function it is essential to generate such a map. Here we describe an advanced mass spectrometry imaging platform to reveal spatial cholesterol metabolism in situ at 400 µm resolution on 10 µm tissue slices from mouse brain. We mapped, not only cholesterol, but also other biologically active sterols arising from cholesterol turnover in both wild type and mice lacking cholesterol 24-hydroxylase (Cyp46a1), the major cholesterol metabolising enzyme.

Expression of p53 during mouse embryogenesis

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 857-865 ◽  
Author(s):  
P. Schmid ◽  
A. Lorenz ◽  
H. Hameister ◽  
M. Montenarh
Keyword(s):  
Gene Expression ◽  
Cellular Differentiation ◽  
Cellular Proliferation ◽  
In Situ Hybridisation ◽  
Terminal Differentiation ◽  
Mouse Embryogenesis ◽  
Differentiated Cells ◽  
The Brain ◽  
P53 Mrna

By in situ hybridisation we have examined the expression of p53 during mouse embryogenesis from day 8.5 to day 18.5 post coitum (p.c.). High levels of p53 mRNA were detected in all cells of the day 8.5 p.c. and 10.5 p.c. mouse embryo. However, at later stages of development, expression became more pronounced during differentiation of specific tissues e.g. of the brain, liver, lung, thymus, intestine, salivary gland and kidney. In cells undergoing terminal differentiation, the level of p53 mRNA declined strongly. In the brain, hybridisation signals were also observed in postmitotic but not yet terminally differentiated cells. Therefore, gene expression of p53 does not appear to be linked with cellular proliferation in this organ. A proposed role for p53 in cellular differentiation is discussed.

scholarly journals IL CONTROLLO NEUROENDOCRINO DEL COMPORTAMENTO ALIMENTARE

2020 ◽  
Author(s):  
Francesco Cavagnini
Keyword(s):  
Gastrointestinal Tract ◽  
Food Intake ◽  
Nutritional Status ◽  
Eating Behavior ◽  
Nucleus Tractus Solitarius ◽  
Peptide Yy ◽  
Releasing Hormone ◽  
Fat Depots ◽  
Adiposity Signals ◽  
The Brain

Appetite is regulated by a complex system of central and peripheral signals that interact in order to modulate eating behavior according the individual needs, i.e. the fasting or fed condition and the general nutritional status. Peripheral regulation includes adiposity signals and satiety signals, while central control is accomplished by several effectors, including the neuropeptidergic, monoaminergic and endocannabinoid systems. Adiposity signals inform the brain of the general nutritional status of the subject as indicated by the extent of fat depots. Indeed, leptin produced by the adipose tissue and insulin, whose pancreatic secretion tends to increase with the increase of fat mass, convey to the brain an anorexigenic message. Satiety signals, including cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), originate from the gastrointestinal tract during a meal and, through the vagus nerve, reach the nucleus tractus solitarius (NTS) in the caudal brainstem. From NTS afferents fibers project to the arcuate nucleus (ARC) of the hypothalamus, where satiety signals are integrated with adiposity signals and with several hypothalamic and supra-hypothalamic inputs, thus creating a complex network of neural circuits that finally elaborate the most appropriate response, in terms of eating behavior. In more detail, ARC neurons secrete a number of neuropeptides with orexigenic properties, such as neuropeptide Y (NPY) and agouti-related peptide (AGRP), or anorexigenic effects such as pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Other brain areas involved in the control of food intake are located downstream the ARC: among these, the paraventricular nucleus (PVN), which produces anorexigenic peptides such as thyrotropin releasing hormone (TRH), corticotrophin releasing hormone (CRH) and oxytocin, the lateral hypothalamus (LHA) and perifornical area (PFA), secreting the orexigenic substances orexin-A (OXA) and melanin concentrating hormone (MCH). Recently, a great interest has developed for endogenous cannabinoids, important players in the regulation of food intake and energy metabolism. In the same context, increasing evidence is accumulating for a role played by the microbiota, the trillion of microorganism populating the human gastrointestinal tract. The complex interaction between the peripheral organs and the central nervous system has generated the concept of gut-brain axis, now incorporated into the physiology. A better understanding of the mechanisms governing the eating behavior will allow the development of drugs capable of reducing or enhancing food consumption.

scholarly journals LGR4 and Its Ligands, R-Spondin 1 and R-Spondin 3, Regulate Food Intake in the Hypothalamus of Male Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 429-440 ◽  
Author(s):  
Ji-Yao Li ◽  
Biaoxin Chai ◽  
Weizhen Zhang ◽  
Danielle M. Fritze ◽  
Chao Zhang ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Energy Homeostasis ◽  
Male Rats ◽  
The Third ◽  
The Brain

The hypothalamus plays a key role in the regulation of feeding behavior. Several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in energy homeostasis. Analysis of microarray data derived from ARC revealed that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors. Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4 subfamily. In the present study, we investigated the distribution and function of LGR4–LGR6 and Rspos (1–4) in the brain of male rat. In situ hybridization showed that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus. LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization; LGR6 is only expressed in the epithelial lining of the lower portion of the third ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated with fasting. Rspo3 is expressed in the paraventricular nucleus and also down-regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD, indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis.

scholarly journals Effect of Metallothionein-III on Mercury-Induced Chemokine Gene Expression

Toxics ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 48 ◽  
Author(s):  
Jin-Yong Lee ◽  
Maki Tokumoto ◽  
Gi-Wook Hwang ◽  
Min-Seok Kim ◽  
Tsutomu Takahashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Mercury Vapor ◽  
Brain Diseases ◽  
Wild Type ◽  
Chemokine Gene ◽  
Mercury Compounds ◽  
In The Wild ◽  
The Brain ◽  
Chemokine Gene Expression

Mercury compounds are known to cause central nervous system disorders; however the detailed molecular mechanisms of their actions remain unclear. Methylmercury increases the expression of several chemokine genes, specifically in the brain, while metallothionein-III (MT-III) has a protective role against various brain diseases. In this study, we investigated the involvement of MT-III in chemokine gene expression changes in response to methylmercury and mercury vapor in the cerebrum and cerebellum of wild-type mice and MT-III null mice. No difference in mercury concentration was observed between the wild-type mice and MT-III null mice in any brain tissue examined. The expression of Ccl3 in the cerebrum and of Cxcl10 in the cerebellum was increased by methylmercury in the MT-III null but not the wild-type mice. The expression of Ccl7 in the cerebellum was increased by mercury vapor in the MT-III null mice but not the wild-type mice. However, the expression of Ccl12 and Cxcl12 was increased in the cerebrum by methylmercury only in the wild-type mice and the expression of Ccl3 in the cerebellum was increased by mercury vapor only in the wild-type mice. These results indicate that MT-III does not affect mercury accumulation in the brain, but that it affects the expression of some chemokine genes in response to mercury compounds.

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.

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