The Experts below are selected from a list of 12351 Experts worldwide ranked by ideXlab platform
Hergen Spits - One of the best experts on this subject based on the ideXlab platform.
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phosphatidylinositol 3 oh kinase and Nutrient Sensing mtor pathways control t lymphocyte trafficking
Nature Immunology, 2008Co-Authors: Linda V Sinclair, Carmen Feijoo, Klaus Okkenhaug, Thijs J Hagenbeek, Alexander Gray, Hergen Spits, David K. Finlay, Ann Ager, Georgina H CornishAbstract:Phosphatidylinositol-3-OH kinase and Nutrient-Sensing mTOR pathways control T lymphocyte trafficking
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phosphatidylinositol 3 oh kinase and Nutrient Sensing mtor pathways control t lymphocyte trafficking
Nature Immunology, 2008Co-Authors: Linda V Sinclair, Carmen Feijoo, Klaus Okkenhaug, Thijs J Hagenbeek, Alexander Gray, Hergen Spits, David K. Finlay, Ann Ager, Georgina H CornishAbstract:Phosphatidylinositol-3-OH kinase (PI(3)K) and the Nutrient sensor mTOR are evolutionarily conserved regulators of cell metabolism. Here we show that PI(3)K and mTOR determined the repertoire of adhesion and chemokine receptors expressed by T lymphocytes. The key lymph node-homing receptors CD62L (L-selectin) and CCR7 were highly expressed on naive T lymphocytes but were downregulated after immune activation. CD62L downregulation occurred through ectodomain proteolysis and suppression of gene transcription. The p110delta subunit of PI(3)K controlled CD62L proteolysis through mitogen-activated protein kinases, whereas control of CD62L transcription by p110delta was mediated by mTOR through regulation of the transcription factor KLF2. PI(3)K-mTOR Nutrient-Sensing pathways also determined expression of the chemokine receptor CCR7 and regulated lymphocyte trafficking in vivo. Hence, lymphocytes use PI(3)K and mTOR to match metabolism and trafficking.
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Corrigendum: phosphatidylinositol-3-OH kinase and Nutrient-Sensing mTOR pathways control T lymphocyte trafficking
Nature Immunology, 2008Co-Authors: Linda V Sinclair, Carmen Feijoo, Klaus Okkenhaug, Thijs J Hagenbeek, Alexander Gray, Hergen Spits, David K. Finlay, Ann Ager, Georgina H Cornish, Doreen A. CantrellAbstract:Corrigendum: Phosphatidylinositol-3-OH kinase and Nutrient-Sensing mTOR pathways control T lymphocyte trafficking
Linda V Sinclair - One of the best experts on this subject based on the ideXlab platform.
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Nutrient Sensing, signal transduction and immune responses
Seminars in immunology, 2016Co-Authors: Jessica F Walls, Linda V Sinclair, David K. FinlayAbstract:Most cells in the body have a constant supply of Nutrients, which are required to sustain cellular metabolism and functions. In contrast, cells of the immune system can encounter conditions with a limited Nutrient supply during the course of an immune response. Cells of the immune system frequently operate in complex Nutrient restricted microenvironments such as tumour or inflammatory sites. The concentrations of key Nutrients such as glucose and certain amino acids, can be low at these sites, and this can have an impact upon immune cell function. Nutrient sufficiency is important to supply the metabolic and biosynthetic pathways of immune cells. In addition Nutrients can also act as important cues that influence immunological signalling pathways to affect the function of immune cells. This review will describe the various Nutrient Sensing signalling pathways and discuss the evidence that Nutrients are critical signals that shape immune responses.
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phosphatidylinositol 3 oh kinase and Nutrient Sensing mtor pathways control t lymphocyte trafficking
Nature Immunology, 2008Co-Authors: Linda V Sinclair, Carmen Feijoo, Klaus Okkenhaug, Thijs J Hagenbeek, Alexander Gray, Hergen Spits, David K. Finlay, Ann Ager, Georgina H CornishAbstract:Phosphatidylinositol-3-OH kinase and Nutrient-Sensing mTOR pathways control T lymphocyte trafficking
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phosphatidylinositol 3 oh kinase and Nutrient Sensing mtor pathways control t lymphocyte trafficking
Nature Immunology, 2008Co-Authors: Linda V Sinclair, Carmen Feijoo, Klaus Okkenhaug, Thijs J Hagenbeek, Alexander Gray, Hergen Spits, David K. Finlay, Ann Ager, Georgina H CornishAbstract:Phosphatidylinositol-3-OH kinase (PI(3)K) and the Nutrient sensor mTOR are evolutionarily conserved regulators of cell metabolism. Here we show that PI(3)K and mTOR determined the repertoire of adhesion and chemokine receptors expressed by T lymphocytes. The key lymph node-homing receptors CD62L (L-selectin) and CCR7 were highly expressed on naive T lymphocytes but were downregulated after immune activation. CD62L downregulation occurred through ectodomain proteolysis and suppression of gene transcription. The p110delta subunit of PI(3)K controlled CD62L proteolysis through mitogen-activated protein kinases, whereas control of CD62L transcription by p110delta was mediated by mTOR through regulation of the transcription factor KLF2. PI(3)K-mTOR Nutrient-Sensing pathways also determined expression of the chemokine receptor CCR7 and regulated lymphocyte trafficking in vivo. Hence, lymphocytes use PI(3)K and mTOR to match metabolism and trafficking.
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Corrigendum: phosphatidylinositol-3-OH kinase and Nutrient-Sensing mTOR pathways control T lymphocyte trafficking
Nature Immunology, 2008Co-Authors: Linda V Sinclair, Carmen Feijoo, Klaus Okkenhaug, Thijs J Hagenbeek, Alexander Gray, Hergen Spits, David K. Finlay, Ann Ager, Georgina H Cornish, Doreen A. CantrellAbstract:Corrigendum: Phosphatidylinositol-3-OH kinase and Nutrient-Sensing mTOR pathways control T lymphocyte trafficking
David K. Finlay - One of the best experts on this subject based on the ideXlab platform.
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Nutrient Sensing, signal transduction and immune responses
Seminars in immunology, 2016Co-Authors: Jessica F Walls, Linda V Sinclair, David K. FinlayAbstract:Most cells in the body have a constant supply of Nutrients, which are required to sustain cellular metabolism and functions. In contrast, cells of the immune system can encounter conditions with a limited Nutrient supply during the course of an immune response. Cells of the immune system frequently operate in complex Nutrient restricted microenvironments such as tumour or inflammatory sites. The concentrations of key Nutrients such as glucose and certain amino acids, can be low at these sites, and this can have an impact upon immune cell function. Nutrient sufficiency is important to supply the metabolic and biosynthetic pathways of immune cells. In addition Nutrients can also act as important cues that influence immunological signalling pathways to affect the function of immune cells. This review will describe the various Nutrient Sensing signalling pathways and discuss the evidence that Nutrients are critical signals that shape immune responses.
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phosphatidylinositol 3 oh kinase and Nutrient Sensing mtor pathways control t lymphocyte trafficking
Nature Immunology, 2008Co-Authors: Linda V Sinclair, Carmen Feijoo, Klaus Okkenhaug, Thijs J Hagenbeek, Alexander Gray, Hergen Spits, David K. Finlay, Ann Ager, Georgina H CornishAbstract:Phosphatidylinositol-3-OH kinase and Nutrient-Sensing mTOR pathways control T lymphocyte trafficking
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phosphatidylinositol 3 oh kinase and Nutrient Sensing mtor pathways control t lymphocyte trafficking
Nature Immunology, 2008Co-Authors: Linda V Sinclair, Carmen Feijoo, Klaus Okkenhaug, Thijs J Hagenbeek, Alexander Gray, Hergen Spits, David K. Finlay, Ann Ager, Georgina H CornishAbstract:Phosphatidylinositol-3-OH kinase (PI(3)K) and the Nutrient sensor mTOR are evolutionarily conserved regulators of cell metabolism. Here we show that PI(3)K and mTOR determined the repertoire of adhesion and chemokine receptors expressed by T lymphocytes. The key lymph node-homing receptors CD62L (L-selectin) and CCR7 were highly expressed on naive T lymphocytes but were downregulated after immune activation. CD62L downregulation occurred through ectodomain proteolysis and suppression of gene transcription. The p110delta subunit of PI(3)K controlled CD62L proteolysis through mitogen-activated protein kinases, whereas control of CD62L transcription by p110delta was mediated by mTOR through regulation of the transcription factor KLF2. PI(3)K-mTOR Nutrient-Sensing pathways also determined expression of the chemokine receptor CCR7 and regulated lymphocyte trafficking in vivo. Hence, lymphocytes use PI(3)K and mTOR to match metabolism and trafficking.
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Corrigendum: phosphatidylinositol-3-OH kinase and Nutrient-Sensing mTOR pathways control T lymphocyte trafficking
Nature Immunology, 2008Co-Authors: Linda V Sinclair, Carmen Feijoo, Klaus Okkenhaug, Thijs J Hagenbeek, Alexander Gray, Hergen Spits, David K. Finlay, Ann Ager, Georgina H Cornish, Doreen A. CantrellAbstract:Corrigendum: Phosphatidylinositol-3-OH kinase and Nutrient-Sensing mTOR pathways control T lymphocyte trafficking
Tony K.t. Lam - One of the best experts on this subject based on the ideXlab platform.
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Small intestinal taurochenodeoxycholic acid-FXR axis alters local Nutrient Sensing glucoregulatory pathways in rats.
Molecular metabolism, 2020Co-Authors: T.m. Zaved Waise, Yu-mi Lim, Zahra Danaei, Song-yang Zhang, Tony K.t. LamAbstract:ABSTRACT OBJECTIVE The mechanism of Nutrient Sensing in the upper small intestine (USI) and ileum that regulate glucose homeostasis remains elusive. Short-term High fat (HF) feeding increases taurochenodeoxycholic acid (TCDCA; an agonist of farnesoid X receptor (FXR)) in the USI and ileum of rats, and the increase of TCDCA is prevented by transplantation of microbiota obtained from the USI of healthy donors into the USI of HF rats. However, whether changes of TCDCA-FXR axis in the USI and ileum alter Nutrient Sensing remains unknown. METHODS Intravenous glucose tolerance test was performed in rats that received USI or ileal infusion of Nutrients (i.e., oleic acids or glucose) via catheters placed towards the lumen of USI and/or ileum, while mechanistic gain & loss-of-function studies targeting TCDCA-FXR axis or bile salt hydrolase activity in USI and ileum were performed. RESULTS USI or ileum infusion of Nutrients increased glucose tolerance in healthy but not HF rats. Transplantation of healthy microbiome obtained from USI into the USI of HF rats restored Nutrient Sensing and inhibited FXR via a reduction of TCDCA in the USI and ileum. Further, inhibition of USI and ileal FXR enhanced Nutrient Sensing in HF rats, while inhibiting USI (but not ileal) bile salt hydrolase of HF rats transplanted with healthy microbiome activated FXR and disrupted Nutrient Sensing in USI and ileum. CONCLUSIONS We unravel a TCDCA-FXR axis in both USI and ileum that is necessary for the upper small intestinal microbiome to govern local Nutrient Sensing glucoregulatory pathways in rats.
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gut microbiota Nutrient Sensing and energy balance
Diabetes Obesity and Metabolism, 2014Co-Authors: Frank A. Duca, Tony K.t. LamAbstract:The gastrointestinal (GI) tract is a highly specialized sensory organ that provides crucial negative feedback during a meal, partly via a gut–brain axis. More specifically, enteroendocrine cells located throughout the GI tract are able to sense and respond to specific Nutrients, releasing gut peptides that act in a paracrine, autocrine or endocrine fashion to regulate energy balance, thus controlling both food intake and possibly energy expenditure. Furthermore, the gut microbiota has been shown to provide a substantial metabolic and physiological contribution to the host, and metabolic disease such as obesity has been associated with aberrant gut microbiota and microbiome. Interestingly, recent evidence suggests that the gut microbiota can impact the gut–brain axis controlling energy balance, at both the level of intestinal Nutrient-Sensing mechanisms, as well as potentially at the sites of integration in the central nervous system. A better understanding of the intricate relationship between the gut microbiota and host energy-regulating pathways is crucial for uncovering the mechanisms responsible for the development of metabolic diseases and for possible therapeutic strategies.
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Nutrient-Sensing Mechanisms in the Gut as Therapeutic Targets for Diabetes
Diabetes, 2013Co-Authors: Danna M. Breen, Brittany A. Rasmussen, Clémence D. Côté, V. Margaret Jackson, Tony K.t. LamAbstract:The small intestine is traditionally viewed as an organ that mediates Nutrient digestion and absorption. This view has recently been revised owing to the ability of the duodenum to sense Nutrient influx and trigger negative feedback loops to inhibit glucose production and food intake to maintain metabolic homeostasis. Further, duodenal Nutrient-Sensing defects are acquired in diabetes and obesity, leading to increased glucose production. In contrast, jejunal Nutrient Sensing inhibits glucose production and mediates the early antidiabetic effect of bariatric surgery, and gut microbiota composition may alter intestinal Nutrient-Sensing mechanisms to regain better control of glucose homeostasis in diabetes and obesity in the long term. This perspective highlights Nutrient-Sensing mechanisms in the gut that regulate glucose homeostasis and the potential of targeting gut Nutrient-Sensing mechanisms as a therapeutic strategy to lower blood glucose concentrations in diabetes.
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Hypothalamic Nutrient Sensing activates a forebrain-hindbrain neuronal circuit to regulate glucose production in vivo
Diabetes, 2010Co-Authors: Carol K.l. Lam, Madhu Chari, Guy A. Rutter, Tony K.t. LamAbstract:Objective – Hypothalamic Nutrient Sensing regulates glucose production but the neuronal circuits involved remain largely unknown. Recent studies underscore the importance of N-methyl-D-aspartate (NMDA) receptors in the dorsal vagal complex in glucose regulation. These studies raise the possibility that hypothalamic Nutrient Sensing activates a forebrain-hindbrain NMDA dependent circuit to regulate glucose production. Research design and methods – We implanted bilateral catheters targeting the mediobasal hypothalamus (MBH; forebrain) and dorsal vagal complex (DVC; hindbrain) and performed i.v. catheterizations to the same rat for infusion and sampling purposes. This model enabled concurrent selective activation of MBH Nutrient Sensing by either MBH delivery of lactate or an adenovirus expressing the dominant negative form of AMPK (Ad-DN AMPK α2 [D157A]) and inhibition of DVC NMDA receptors by either DVC delivery of NMDA receptor blocker MK-801 or an adenovirus expressing the shRNA of NR1 subunit of NMDA receptors (Ad-shRNA NR1). Tracer-dilution methodology and the pancreatic euglycemic clamp technique were performed to assess changes in glucose kinetics in the same conscious, unrestrained rat in vivo . Results – MBH lactate or Ad-DN AMPK with DVC saline increased glucose infusion required to maintain euglycemia due to an inhibition of glucose production during the clamps. However, DVC MK-801 negated the ability of MBH lactate or Ad-DN AMPK to increase glucose infusion and lower glucose production. Molecular knockdown of DVC NR1 of NMDA receptor via Ad-shRNA NR1 injection also negated MBH Ad-DN AMPK to lower glucose production. Conclusions – Molecular and pharmacological inhibition of DVC NMDA receptors negated hypothalamic Nutrient Sensing mechanisms activated by lactate metabolism or AMPK inhibition to lower glucose production. Thus, DVC NMDA receptor is required for hypothalamic Nutrient Sensing to lower glucose production and that hypothalamic Nutrient Sensing activates a forebrain-hindbrain circuit to lower glucose production.
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Neuronal regulation of homeostasis by Nutrient Sensing.
Nature medicine, 2010Co-Authors: Tony K.t. LamAbstract:In type 2 diabetes and obesity, the homeostatic control of glucose and energy balance is impaired, leading to hyperglycemia and hyperphagia. Recent studies indicate that Nutrient-Sensing mechanisms in the body activate negative-feedback systems to regulate energy and glucose homeostasis through a neuronal network. Direct metabolic signaling within the intestine activates gut-brain and gut-brain-liver axes to regulate energy and glucose homeostasis, respectively. In parallel, direct metabolism of Nutrients within the hypothalamus regulates food intake and blood glucose levels. These findings highlight the importance of the central nervous system in mediating the ability of Nutrient Sensing to maintain homeostasis. Futhermore, they provide a physiological and neuronal framework by which enhancing or restoring Nutrient Sensing in the intestine and the brain could normalize energy and glucose homeostasis in diabetes and obesity.
Clemence Blouet - One of the best experts on this subject based on the ideXlab platform.
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Nutrient Sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons.
Molecular metabolism, 2020Co-Authors: Anthony H Tsang, Tamana Darwish, Havish Samudrala, Danae Nuzzaci, Clemence BlouetAbstract:Abstract The nucleus of the solitary tract (NTS) is emerging as a major site of action for the appetite-suppressive effects of leading pharmacotherapies currently investigated to treat obesity. However, our understanding of how NTS neurons regulate appetite remains incomplete. Objectives In this study, we used NTS Nutrient Sensing as an entry point to characterize stimulus-defined neuronal ensembles engaged by the NTS to produce physiological satiety. Methods We combined histological analysis, neuroanatomical assessment using inducible viral tracing tools, and functional tests to characterize hindbrain-forebrain circuits engaged by NTS leucine Sensing to suppress hunger. Results We found that NTS detection of leucine engages NTS prolactin-releasing peptide (PrRP) neurons to inhibit AgRP neurons via a population of leptin receptor-expressing neurons in the dorsomedial hypothalamus. This circuit is necessary for the anorectic response to NTS leucine, the appetite-suppressive effect of high-protein diets, and the long-term control of energy balance. Conclusions These results extend the integrative capability of AgRP neurons to include brainstem Nutrient Sensing inputs.
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Nutrient Sensing in the nucleus od the solitary tract mediates non aversive suppression of feeding via inhibition of agrp neurons
bioRxiv, 2020Co-Authors: Anthony H Tsang, Danae Nuzacci, Tamana Darwish, Havish Samudrala, Clemence BlouetAbstract:The nucleus of the solitary tract (NTS) is emerging as a major site of action for the appetite-suppressive effects of leading pharmacotherapies currently investigated for the treatment of obesity. However, our understanding of how NTS neurons regulate appetite remains incomplete. Here we used NTS Nutrient Sensing as an entry point to characterize stimulus-defined neuronal ensembles engaged by the NTS to produce physiological satiety. Using activity-dependent expression of genetically-encoded circuit analysis tools, we found that NTS detection of leucine engages NTS prolactin-releasing peptide (PrRP) neurons to inhibit AgRP neurons via a population of leptin-receptor-expressing neurons in the dorsomedial hypothalamus. This circuit is necessary for the anorectic response to NTS leucine, the appetite-suppressive effect of high protein diets, and the long-term control of energy balance. These results extends the integrative capability of AgRP neurons to include brainstem Nutrient Sensing inputs.
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Nutrient Sensing hypothalamic txnip links Nutrient excess to energy imbalance in mice
The Journal of Neuroscience, 2011Co-Authors: Clemence Blouet, Gary J SchwartzAbstract:Nutrient excess in obesity and diabetes is emerging as a common putative cause for multiple deleterious effects across diverse cell types, responsible for a variety of metabolic dysfunctions. The hypothalamus is acknowledged as an important regulator of whole-body energy homeostasis, through both detection of Nutrient availability and coordination of effectors that determine Nutrient intake and utilization, thus preventing cellular and whole-body Nutrient excess. However, the mechanisms underlying hypothalamic Nutrient detection and its impact on peripheral Nutrient utilization remain poorly understood. Recent data suggest a role for thioredoxin-interacting protein (TXNIP) as a molecular Nutrient sensor important in the regulation of energy metabolism, but the role of hypothalamic TXNIP in the regulation of energy balance has not been evaluated. Here we show in mice that TXNIP is expressed in Nutrient-Sensing neurons of the mediobasal hypothalamus, responds to hormonal and Nutrient signals, and regulates adipose tissue metabolism, fuel partitioning, and glucose homeostasis. Hypothalamic expression of TXNIP is induced by acute Nutrient excess and in mouse models of obesity and diabetes, and downregulation of mediobasal hypothalamic TXNIP expression prevents diet-induced obesity and insulin resistance. Thus, mediobasal hypothalamic TXNIP plays a critical role in Nutrient Sensing and the regulation of fuel utilization.
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Hypothalamic Nutrient Sensing in the control of energy homeostasis.
Behavioural brain research, 2009Co-Authors: Clemence Blouet, Gary J SchwartzAbstract:The hypothalamus is a center of convergence and integration of multiple Nutrient-related signals. It can sense changes in circulating adiposity hormones, gastric hormones and Nutrients, and receives neuroanatomical projections from other Nutrient sensors, mainly within the brainstem. The hypothalamus also integrates these signals with various cognitive forebrain-descending information and reward/motivation-related signals coming from the midbrain-dopamine system, to coordinate neuroendocrine, behavioral and metabolic effectors of energy balance. Some of the key Nutrient-Sensing hypothalamic neurons have been identified in the arcuate, the ventro-medial and the lateral nuclei of the hypothalamus, and the molecular mechanisms underlying intracellular integration of Nutrient-related signals in these neurons are currently under intensive investigation. However, little is known about the neural pathways downstream from hypothalamic Nutrient sensors, and how they drive effectors of energy homeostasis under physiological conditions. This manuscript will review recent progress from molecular, genetic and neurophysiological studies that identify and characterize the critical intracellular signalling pathways and neurocircuits involved in determining hypothalamic Nutrient detection, and link these circuits to behavioral and metabolic effectors of energy balance. We will provide a critical analysis of current data to identify ongoing challenges for future research in this field.
