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Homeostasis

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Homeostasis - Free Register to Access Experts & Abstracts

Yong Xu - One of the best experts on this subject based on the ideXlab platform.

  • serotonin 2c receptors in pro opiomelanocortin neurons regulate energy and glucose Homeostasis
    Journal of Clinical Investigation, 2013
    Co-Authors: Eric D Berglund, Jong Woo Sohn, Claudia R Vianna, Kevin W Williams, Yong Xu, Joel K Elmquist
    Abstract:

    Energy and glucose Homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose Homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose Homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose Homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.

  • 5 ht2crs expressed by pro opiomelanocortin neurons regulate insulin sensitivity in liver
    Nature Neuroscience, 2010
    Co-Authors: William L Holland, Jari Rossi, Eric D Berglund, Jong Woo Sohn, Kevin W Williams, Makoto Fukuda, Jen Chieh Chuang, Yong Xu, Juli E Jones
    Abstract:

    5-hydroxytryptamine 2C receptors (5-HT2CRs) in the brain have been shown to regulate glucose Homeostasis. Xu and colleagues find that 5-HT2CRs expressed specifically by hypothalamic pro-opiomelanocortin neurons are involved in the regulation of insulin sensitivity and glucose Homeostasis in liver.

Adolfo Saiardi - One of the best experts on this subject based on the ideXlab platform.

  • the inositol hexakisphosphate kinases ip6k1 and 2 regulate human cellular phosphate Homeostasis including xpr1 mediated phosphate export
    Journal of Biological Chemistry, 2019
    Co-Authors: Miranda S C Wilson, Henning J Jessen, Adolfo Saiardi
    Abstract:

    Phosphate's central role in most biochemical reactions in a living organism requires carefully maintained phosphate Homeostasis. Although phosphate Homeostasis in mammals has long been studied at the organismal level, the intracellular mechanisms controlling phosphate metabolism are not well understood. Inositol pyrophosphates have emerged as important regulatory elements controlling yeast phosphate Homeostasis. To verify whether inositol pyrophosphates also regulate mammalian cellular phosphate Homeostasis, here we knocked out inositol hexakisphosphate kinase (IP6K) 1 and IP6K2 to generate human HCT116 cells devoid of any inositol pyrophosphates. Using  PAGE and HPLC analysis, we observed that the IP6K1/2-knockout cells have non-detectable levels of the IP6-derived IP7 and IP8 and also exhibit reduced synthesis of the IP5-derived PP-IP4 Nucleotide analysis showed that the knockout cells contain increased amounts of ATP, while the Malachite green assay found elevated levels of free intracellular phosphate. Furthermore, [32Pi] pulse labeling experiments uncovered alterations in phosphate flux, with both import and export of phosphate being decreased in the knockout cells. Functional analysis of the phosphate exporter xenotropic and polytropic retrovirus receptor 1 (XPR1) revealed that it is regulated by inositol pyrophosphates, which can bind to its SPX domain. We conclude that IP6K1 and -2 together control inositol pyrophosphate metabolism and thereby physiologically regulate phosphate export and other aspects of mammalian cellular phosphate Homeostasis.

  • eukaryotic phosphate Homeostasis the inositol pyrophosphate perspective
    Trends in Biochemical Sciences, 2017
    Co-Authors: Cristina Azevedo, Adolfo Saiardi
    Abstract:

    Phosphate, as a cellular energy currency, essentially drives most biochemical reactions defining living organisms, and thus its Homeostasis must be tightly regulated. Investigation into the role of inositol pyrophosphates (PP-IPs) has provided a novel perspective on the regulation of phosphate Homeostasis. Recent data suggest that metabolic and signaling interplay between PP-IPs, ATP, and inorganic polyphosphate (polyP) influences and is influenced by cellular phosphate Homeostasis. Different studies have demonstrated that the SPX protein domain is a key component of proteins involved in phosphate metabolism. How PP-IPs control some aspects of phosphate Homeostasis has become clearer with the recently acquired crystal structures of SPX domains. We review here recent studies on eukaryote phosphate Homeostasis and provide insights into future research.

Eric D Berglund - One of the best experts on this subject based on the ideXlab platform.

  • serotonin 2c receptors in pro opiomelanocortin neurons regulate energy and glucose Homeostasis
    Journal of Clinical Investigation, 2013
    Co-Authors: Eric D Berglund, Jong Woo Sohn, Claudia R Vianna, Kevin W Williams, Yong Xu, Joel K Elmquist
    Abstract:

    Energy and glucose Homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose Homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose Homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose Homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.

  • 5 ht2crs expressed by pro opiomelanocortin neurons regulate insulin sensitivity in liver
    Nature Neuroscience, 2010
    Co-Authors: William L Holland, Jari Rossi, Eric D Berglund, Jong Woo Sohn, Kevin W Williams, Makoto Fukuda, Jen Chieh Chuang, Yong Xu, Juli E Jones
    Abstract:

    5-hydroxytryptamine 2C receptors (5-HT2CRs) in the brain have been shown to regulate glucose Homeostasis. Xu and colleagues find that 5-HT2CRs expressed specifically by hypothalamic pro-opiomelanocortin neurons are involved in the regulation of insulin sensitivity and glucose Homeostasis in liver.

Robert A Egnatchik - One of the best experts on this subject based on the ideXlab platform.

  • abstract a17 glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox Homeostasis and tumor growth
    Molecular Cancer Research, 2016
    Co-Authors: Dan Li, Gina N Alesi, Kelly R Magliocca, Hee-bum Kang, Robert A Egnatchik, Titus J Boggon, Ralph J Deberardinis, Chuan He, Lu Zhou, Martha Arellano
    Abstract:

    How mitochondrial glutaminolysis contributes to redox Homeostasis in cancer cells remains unclear. Here we report that the mitochondrial enzyme glutamate dehydrogenase 1 (GDH1), commonly upregulated in human cancers, is predominantly important for redox Homeostasis in cancer cells by controlling the intracellular levels of its product alpha-ketoglutarate (a-KG) and subsequent metabolite fumarate. Mechanistically, fumarate binds to and activates a ROS scavenging enzyme glutathione peroxidase 1 (GPx1) to regulate redox Homeostasis, which provides a proliferative advantage to cancer cells and tumor growth. Our findings not only provide novel insights into understanding of the role of glutaminolysis in redox Homeostasis but also suggest a novel signaling function of fumarate that regulates GPx1, allowing additional crosstalk between glutaminolysis, TCA cycle and redox status. Targeting GDH1 by shRNA or a newly identified small molecule inhibitor R162 resulted in imbalanced redox Homeostasis, leading to attenuated cancer cell proliferation and tumor growth. Thus, our findings provide proof-of-principle suggesting GDH1 as a promising therapeutic target in the treatment of human cancers associated with elevated glutamine metabolism. Citation Format: Lingtao Jin, Dan Li, Gina Alesi, Jun Fan, Hee-Bum Kang, Lu Zhou, Titus Boggon, Peng Jin, Robert Egnatchik, Ralph DeBerardinis, Kelly Magliocca, Chuan He, Martha Arellano, Hanna Khoury, Dong Shin, Fadlo Khuri, Sumin Kang. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox Homeostasis and tumor growth. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A17.

  • glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox Homeostasis and tumor growth
    Cancer Cell, 2015
    Co-Authors: Dan Li, Gina N Alesi, Elizabeth R. Wright, Duc M Duong, Hee-bum Kang, Nicholas T. Seyfried, Titus J Boggon, Zhou Lu, Hong Yi, Robert A Egnatchik
    Abstract:

    Summary How mitochondrial glutaminolysis contributes to redox Homeostasis in cancer cells remains unclear. Here we report that the mitochondrial enzyme glutamate dehydrogenase 1 (GDH1) is commonly upregulated in human cancers. GDH1 is important for redox Homeostasis in cancer cells by controlling the intracellular levels of its product alpha-ketoglutarate and subsequent metabolite fumarate. Mechanistically, fumarate binds to and activates a reactive oxygen species scavenging enzyme glutathione peroxidase 1. Targeting GDH1 by shRNA or a small molecule inhibitor R162 resulted in imbalanced redox Homeostasis, leading to attenuated cancer cell proliferation and tumor growth.

Dan Li - One of the best experts on this subject based on the ideXlab platform.

  • abstract a17 glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox Homeostasis and tumor growth
    Molecular Cancer Research, 2016
    Co-Authors: Dan Li, Gina N Alesi, Kelly R Magliocca, Hee-bum Kang, Robert A Egnatchik, Titus J Boggon, Ralph J Deberardinis, Chuan He, Lu Zhou, Martha Arellano
    Abstract:

    How mitochondrial glutaminolysis contributes to redox Homeostasis in cancer cells remains unclear. Here we report that the mitochondrial enzyme glutamate dehydrogenase 1 (GDH1), commonly upregulated in human cancers, is predominantly important for redox Homeostasis in cancer cells by controlling the intracellular levels of its product alpha-ketoglutarate (a-KG) and subsequent metabolite fumarate. Mechanistically, fumarate binds to and activates a ROS scavenging enzyme glutathione peroxidase 1 (GPx1) to regulate redox Homeostasis, which provides a proliferative advantage to cancer cells and tumor growth. Our findings not only provide novel insights into understanding of the role of glutaminolysis in redox Homeostasis but also suggest a novel signaling function of fumarate that regulates GPx1, allowing additional crosstalk between glutaminolysis, TCA cycle and redox status. Targeting GDH1 by shRNA or a newly identified small molecule inhibitor R162 resulted in imbalanced redox Homeostasis, leading to attenuated cancer cell proliferation and tumor growth. Thus, our findings provide proof-of-principle suggesting GDH1 as a promising therapeutic target in the treatment of human cancers associated with elevated glutamine metabolism. Citation Format: Lingtao Jin, Dan Li, Gina Alesi, Jun Fan, Hee-Bum Kang, Lu Zhou, Titus Boggon, Peng Jin, Robert Egnatchik, Ralph DeBerardinis, Kelly Magliocca, Chuan He, Martha Arellano, Hanna Khoury, Dong Shin, Fadlo Khuri, Sumin Kang. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox Homeostasis and tumor growth. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A17.

  • glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox Homeostasis and tumor growth
    Cancer Cell, 2015
    Co-Authors: Dan Li, Gina N Alesi, Elizabeth R. Wright, Duc M Duong, Hee-bum Kang, Nicholas T. Seyfried, Titus J Boggon, Zhou Lu, Hong Yi, Robert A Egnatchik
    Abstract:

    Summary How mitochondrial glutaminolysis contributes to redox Homeostasis in cancer cells remains unclear. Here we report that the mitochondrial enzyme glutamate dehydrogenase 1 (GDH1) is commonly upregulated in human cancers. GDH1 is important for redox Homeostasis in cancer cells by controlling the intracellular levels of its product alpha-ketoglutarate and subsequent metabolite fumarate. Mechanistically, fumarate binds to and activates a reactive oxygen species scavenging enzyme glutathione peroxidase 1. Targeting GDH1 by shRNA or a small molecule inhibitor R162 resulted in imbalanced redox Homeostasis, leading to attenuated cancer cell proliferation and tumor growth.