Antibody-Mediated Inhibition of the FGFR1c Isoform Induces a Catabolic Lean State in Siberian Hamsters

Ricardo J Samms, Jo E Lewis, Alex Lory, Maxine J Fowler, Scott Cooper, Amy Warner, Paul Emmerson, Andrew C Adams, Jeni C Luckett, Alan C Perkins, Dana Wilson, Perry Barrett, Kostas Tsintzas, Francis J P Ebling

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Hypothalamic tanycytes are considered to function as sensors of peripheral metabolism [1]. To facilitate this role, they express a wide range of receptors, including fibroblast growth factor receptor 1 (FGFR1). Using a monoclonal antibody (IMC-H7) that selectively antagonizes the FGFR1c isoform [2], we investigated possible actions of FGFR1c in a natural animal model of adiposity, the Siberian hamster. Infusion of IMC-H7 into the third ventricle suppressed appetite and increased energy expenditure. Likewise, peripheral treatment with IMC-H7 decreased appetite and body weight and increased energy expenditure and fat oxidation. A greater reduction in body weight and caloric intake was observed in response to IMC-H7 during the long-day fat state as compared to the short-day lean state. This enhanced response to IMC-H7 was also observed in calorically restricted hamsters maintained in long days, suggesting that it is the central photoperiodic state rather than the peripheral adiposity that determines the response to FGFR1c antagonism. Hypothalamic thyroid hormone availability is controlled by deiodinase enzymes (DIO2 and DIO3) expressed in tanycytes and is the key regulator of seasonal cycles of energy balance [3, 4]. Therefore, we determined the effect of IMC-H7 on hypothalamic expression of these deiodinase enzymes. The reductions in food intake and body weight were always associated with decreased expression of DIO2 in the hypothalamic ependymal cell layer containing tanycytes. These data provide further support for the notion the tanycytes are an important component of the mechanism by which the hypothalamus integrates central and peripheral signals to regulate energy intake and expenditure.

Original languageEnglish
Pages (from-to)2997-3003
Number of pages7
JournalCurrent Biology
Volume25
Issue number22
Early online date5 Nov 2015
DOIs
Publication statusPublished - 16 Nov 2015

Fingerprint

Phodopus
Ependymoglial Cells
hamsters
energy expenditure
Iodide Peroxidase
Protein Isoforms
adiposity
Energy Metabolism
appetite
antibodies
body weight
Antibodies
energy intake
Body Weight
Adiposity
Appetite
Energy Intake
Fats
hypothalamic hormones
Receptor, Fibroblast Growth Factor, Type 1

Keywords

  • Siberian hamsters
  • FGFR1c
  • Antibody-Mediated Inhibition

Cite this

Samms, R. J., Lewis, J. E., Lory, A., Fowler, M. J., Cooper, S., Warner, A., ... Ebling, F. J. P. (2015). Antibody-Mediated Inhibition of the FGFR1c Isoform Induces a Catabolic Lean State in Siberian Hamsters. Current Biology, 25(22), 2997-3003. https://doi.org/10.1016/j.cub.2015.10.010

Antibody-Mediated Inhibition of the FGFR1c Isoform Induces a Catabolic Lean State in Siberian Hamsters. / Samms, Ricardo J; Lewis, Jo E; Lory, Alex; Fowler, Maxine J; Cooper, Scott; Warner, Amy; Emmerson, Paul; Adams, Andrew C; Luckett, Jeni C; Perkins, Alan C; Wilson, Dana; Barrett, Perry; Tsintzas, Kostas; Ebling, Francis J P.

In: Current Biology, Vol. 25, No. 22, 16.11.2015, p. 2997-3003.

Research output: Contribution to journalArticle

Samms, RJ, Lewis, JE, Lory, A, Fowler, MJ, Cooper, S, Warner, A, Emmerson, P, Adams, AC, Luckett, JC, Perkins, AC, Wilson, D, Barrett, P, Tsintzas, K & Ebling, FJP 2015, 'Antibody-Mediated Inhibition of the FGFR1c Isoform Induces a Catabolic Lean State in Siberian Hamsters', Current Biology, vol. 25, no. 22, pp. 2997-3003. https://doi.org/10.1016/j.cub.2015.10.010
Samms, Ricardo J ; Lewis, Jo E ; Lory, Alex ; Fowler, Maxine J ; Cooper, Scott ; Warner, Amy ; Emmerson, Paul ; Adams, Andrew C ; Luckett, Jeni C ; Perkins, Alan C ; Wilson, Dana ; Barrett, Perry ; Tsintzas, Kostas ; Ebling, Francis J P. / Antibody-Mediated Inhibition of the FGFR1c Isoform Induces a Catabolic Lean State in Siberian Hamsters. In: Current Biology. 2015 ; Vol. 25, No. 22. pp. 2997-3003.
@article{ccb6206311e34ae186bec823db7859c0,
title = "Antibody-Mediated Inhibition of the FGFR1c Isoform Induces a Catabolic Lean State in Siberian Hamsters",
abstract = "Hypothalamic tanycytes are considered to function as sensors of peripheral metabolism [1]. To facilitate this role, they express a wide range of receptors, including fibroblast growth factor receptor 1 (FGFR1). Using a monoclonal antibody (IMC-H7) that selectively antagonizes the FGFR1c isoform [2], we investigated possible actions of FGFR1c in a natural animal model of adiposity, the Siberian hamster. Infusion of IMC-H7 into the third ventricle suppressed appetite and increased energy expenditure. Likewise, peripheral treatment with IMC-H7 decreased appetite and body weight and increased energy expenditure and fat oxidation. A greater reduction in body weight and caloric intake was observed in response to IMC-H7 during the long-day fat state as compared to the short-day lean state. This enhanced response to IMC-H7 was also observed in calorically restricted hamsters maintained in long days, suggesting that it is the central photoperiodic state rather than the peripheral adiposity that determines the response to FGFR1c antagonism. Hypothalamic thyroid hormone availability is controlled by deiodinase enzymes (DIO2 and DIO3) expressed in tanycytes and is the key regulator of seasonal cycles of energy balance [3, 4]. Therefore, we determined the effect of IMC-H7 on hypothalamic expression of these deiodinase enzymes. The reductions in food intake and body weight were always associated with decreased expression of DIO2 in the hypothalamic ependymal cell layer containing tanycytes. These data provide further support for the notion the tanycytes are an important component of the mechanism by which the hypothalamus integrates central and peripheral signals to regulate energy intake and expenditure.",
keywords = "Siberian hamsters, FGFR1c, Antibody-Mediated Inhibition",
author = "Samms, {Ricardo J} and Lewis, {Jo E} and Alex Lory and Fowler, {Maxine J} and Scott Cooper and Amy Warner and Paul Emmerson and Adams, {Andrew C} and Luckett, {Jeni C} and Perkins, {Alan C} and Dana Wilson and Perry Barrett and Kostas Tsintzas and Ebling, {Francis J P}",
note = "Acknowledgments Studies followed the ARRIVE guidelines [29] and were carried out in accordance with the UK Animals (Scientific Procedures) Act of 1986 (project licence PPL 40/3604) and approved by the University of Nottingham Animal Welfare and Ethical Review Board. These studies were funded by the Biotechnology and Biological Sciences Research Council (BBSRC UK) via project grant BB/M001555/1, a doctoral training award (R.J.S.), and a Strategic Skills Award, and additional research costs and reagents were provided by Eli Lilly. R.J.S., P.E., and A.C.A. are currently employees of Eli Lilly and Company. Copyright {\circledC} 2015 Elsevier Ltd. All rights reserved.",
year = "2015",
month = "11",
day = "16",
doi = "10.1016/j.cub.2015.10.010",
language = "English",
volume = "25",
pages = "2997--3003",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "22",

}

TY - JOUR

T1 - Antibody-Mediated Inhibition of the FGFR1c Isoform Induces a Catabolic Lean State in Siberian Hamsters

AU - Samms, Ricardo J

AU - Lewis, Jo E

AU - Lory, Alex

AU - Fowler, Maxine J

AU - Cooper, Scott

AU - Warner, Amy

AU - Emmerson, Paul

AU - Adams, Andrew C

AU - Luckett, Jeni C

AU - Perkins, Alan C

AU - Wilson, Dana

AU - Barrett, Perry

AU - Tsintzas, Kostas

AU - Ebling, Francis J P

N1 - Acknowledgments Studies followed the ARRIVE guidelines [29] and were carried out in accordance with the UK Animals (Scientific Procedures) Act of 1986 (project licence PPL 40/3604) and approved by the University of Nottingham Animal Welfare and Ethical Review Board. These studies were funded by the Biotechnology and Biological Sciences Research Council (BBSRC UK) via project grant BB/M001555/1, a doctoral training award (R.J.S.), and a Strategic Skills Award, and additional research costs and reagents were provided by Eli Lilly. R.J.S., P.E., and A.C.A. are currently employees of Eli Lilly and Company. Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2015/11/16

Y1 - 2015/11/16

N2 - Hypothalamic tanycytes are considered to function as sensors of peripheral metabolism [1]. To facilitate this role, they express a wide range of receptors, including fibroblast growth factor receptor 1 (FGFR1). Using a monoclonal antibody (IMC-H7) that selectively antagonizes the FGFR1c isoform [2], we investigated possible actions of FGFR1c in a natural animal model of adiposity, the Siberian hamster. Infusion of IMC-H7 into the third ventricle suppressed appetite and increased energy expenditure. Likewise, peripheral treatment with IMC-H7 decreased appetite and body weight and increased energy expenditure and fat oxidation. A greater reduction in body weight and caloric intake was observed in response to IMC-H7 during the long-day fat state as compared to the short-day lean state. This enhanced response to IMC-H7 was also observed in calorically restricted hamsters maintained in long days, suggesting that it is the central photoperiodic state rather than the peripheral adiposity that determines the response to FGFR1c antagonism. Hypothalamic thyroid hormone availability is controlled by deiodinase enzymes (DIO2 and DIO3) expressed in tanycytes and is the key regulator of seasonal cycles of energy balance [3, 4]. Therefore, we determined the effect of IMC-H7 on hypothalamic expression of these deiodinase enzymes. The reductions in food intake and body weight were always associated with decreased expression of DIO2 in the hypothalamic ependymal cell layer containing tanycytes. These data provide further support for the notion the tanycytes are an important component of the mechanism by which the hypothalamus integrates central and peripheral signals to regulate energy intake and expenditure.

AB - Hypothalamic tanycytes are considered to function as sensors of peripheral metabolism [1]. To facilitate this role, they express a wide range of receptors, including fibroblast growth factor receptor 1 (FGFR1). Using a monoclonal antibody (IMC-H7) that selectively antagonizes the FGFR1c isoform [2], we investigated possible actions of FGFR1c in a natural animal model of adiposity, the Siberian hamster. Infusion of IMC-H7 into the third ventricle suppressed appetite and increased energy expenditure. Likewise, peripheral treatment with IMC-H7 decreased appetite and body weight and increased energy expenditure and fat oxidation. A greater reduction in body weight and caloric intake was observed in response to IMC-H7 during the long-day fat state as compared to the short-day lean state. This enhanced response to IMC-H7 was also observed in calorically restricted hamsters maintained in long days, suggesting that it is the central photoperiodic state rather than the peripheral adiposity that determines the response to FGFR1c antagonism. Hypothalamic thyroid hormone availability is controlled by deiodinase enzymes (DIO2 and DIO3) expressed in tanycytes and is the key regulator of seasonal cycles of energy balance [3, 4]. Therefore, we determined the effect of IMC-H7 on hypothalamic expression of these deiodinase enzymes. The reductions in food intake and body weight were always associated with decreased expression of DIO2 in the hypothalamic ependymal cell layer containing tanycytes. These data provide further support for the notion the tanycytes are an important component of the mechanism by which the hypothalamus integrates central and peripheral signals to regulate energy intake and expenditure.

KW - Siberian hamsters

KW - FGFR1c

KW - Antibody-Mediated Inhibition

U2 - 10.1016/j.cub.2015.10.010

DO - 10.1016/j.cub.2015.10.010

M3 - Article

VL - 25

SP - 2997

EP - 3003

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 22

ER -