Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms.

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  • Additional Information
    • Author-Supplied Keywords:
      Biochemistry
      Biology and life sciences
      Body weight
      Cytokines
      Developmental biology
      Diabetic endocrinology
      Drug discovery
      Drug research and development
      Endocrine physiology
      Endocrinology
      Hormones
      Immune physiology
      Insulin
      Insulin resistance
      Medicine and health sciences
      Molecular development
      Obesity
      Pharmacodynamics
      Pharmacology
      Physiological parameters
      Physiology
      Research Article
    • NAICS/Industry Codes:
      112990 All Other Animal Production
    • Abstract:
      We have generated a novel monoclonal antibody targeting human FGFR1c (R1c mAb) that caused profound body weight and body fat loss in diet-induced obese mice due to decreased food intake (with energy expenditure unaltered), in turn improving glucose control. R1c mAb also caused weight loss in leptin-deficient ob/ob mice, leptin receptor-mutant db/db mice, and in mice lacking either the melanocortin 4 receptor or the melanin-concentrating hormone receptor 1. In addition, R1c mAb did not change hypothalamic mRNA expression levels of Agrp, Cart, Pomc, Npy, Crh, Mch, or Orexin, suggesting that R1c mAb could cause food intake inhibition and body weight loss via other mechanisms in the brain. Interestingly, peripherally administered R1c mAb accumulated in the median eminence, adjacent arcuate nucleus and in the circumventricular organs where it activated the early response gene c-Fos. As a plausible mechanism and coinciding with the initiation of food intake suppression, R1c mAb induced hypothalamic expression levels of the cytokines Monocyte chemoattractant protein 1 and 3 and ERK1/2 and p70 S6 kinase 1 activation. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • Author Affiliations:
      1Cardiovascular & Metabolic Disease Innovative Medicines, Dept of Bioscience Diabetes, AstraZeneca, Mölndal, Sweden
      2Discovery Sciences Transgenics, AstraZeneca, Mölndal, Sweden
      3Antibody Discovery and Protein Engineering, MedImmune, Cambridge, United Kingdom
      4Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Baton Rouge, United States of America
      5AstraZeneca, Discovery Sciences, Mereside, Alderley Park, Macclesfield, Cheshire, United Kingdom
    • ISSN:
      1932-6203
    • Accession Number:
      10.1371/journal.pone.0112109
    • Accession Number:
      99732929
  • Citations
    • ABNT:
      LELLIOTT, C. J. et al. Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms. PLoS ONE, [s. l.], v. 9, n. 11, p. 1–26, 2014. Disponível em: . Acesso em: 14 nov. 2019.
    • AMA:
      Lelliott CJ, Ahnmark A, Admyre T, et al. Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms. PLoS ONE. 2014;9(11):1-26. doi:10.1371/journal.pone.0112109.
    • APA:
      Lelliott, C. J., Ahnmark, A., Admyre, T., Ahlstedt, I., Irving, L., Keyes, F., … Lindén, D. (2014). Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms. PLoS ONE, 9(11), 1–26. https://doi.org/10.1371/journal.pone.0112109
    • Chicago/Turabian: Author-Date:
      Lelliott, Christopher J., Andrea Ahnmark, Therese Admyre, Ingela Ahlstedt, Lorraine Irving, Feenagh Keyes, Laurel Patterson, et al. 2014. “Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms.” PLoS ONE 9 (11): 1–26. doi:10.1371/journal.pone.0112109.
    • Harvard:
      Lelliott, C. J. et al. (2014) ‘Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms’, PLoS ONE, 9(11), pp. 1–26. doi: 10.1371/journal.pone.0112109.
    • Harvard: Australian:
      Lelliott, CJ, Ahnmark, A, Admyre, T, Ahlstedt, I, Irving, L, Keyes, F, Patterson, L, Mumphrey, MB, Bjursell, M, Gorman, T, Bohlooly-Y, M, Buchanan, A, Harrison, P, Vaughan, T, Berthoud, H-R & Lindén, D 2014, ‘Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms’, PLoS ONE, vol. 9, no. 11, pp. 1–26, viewed 14 November 2019, .
    • MLA:
      Lelliott, Christopher J., et al. “Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms.” PLoS ONE, vol. 9, no. 11, Nov. 2014, pp. 1–26. EBSCOhost, doi:10.1371/journal.pone.0112109.
    • Chicago/Turabian: Humanities:
      Lelliott, Christopher J., Andrea Ahnmark, Therese Admyre, Ingela Ahlstedt, Lorraine Irving, Feenagh Keyes, Laurel Patterson, et al. “Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms.” PLoS ONE 9, no. 11 (November 2014): 1–26. doi:10.1371/journal.pone.0112109.
    • Vancouver/ICMJE:
      Lelliott CJ, Ahnmark A, Admyre T, Ahlstedt I, Irving L, Keyes F, et al. Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms. PLoS ONE [Internet]. 2014 Nov [cited 2019 Nov 14];9(11):1–26. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=aph&AN=99732929