Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons

Brandon L. Roberts, Baylin J. Bennett, Camdin M. Bennett, Julie M. Carroll, Louise S. Dalbøge, Colin Hall, Wafa Hassouneh, Kristy M. Heppner, Melissa A. Kirigiti, Sarah R. Lindsley, Katherine G. Tennant, Cadence A. True, Andrew Whittle, Anitra C. Wolf, Charles Roberts, Mads Tang-Christensen, Mark W. Sleeman, Michael A. Cowley, Kevin Grove, Paul Kievit

Research output: Contribution to journalArticle

Abstract

Objective: Reelin (RELN) is a large glycoprotein involved in synapse maturation and neuronal organization throughout development. Deficits in RELN signaling contribute to multiple psychological disorders, such as autism spectrum disorder, schizophrenia, and bipolar disorder. Nutritional stress alters RELN expression in brain regions associated with these disorders; however, the involvement of RELN in the neural circuits involved in energy metabolism is unknown. The RELN receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are involved in lipid metabolism and expressed in the hypothalamus. Here we explored the involvement of RELN in hypothalamic signaling and the impact of diet-induced obesity (DIO) on this system. Methods: Adult male mice were fed a chow diet or maintained on a high-fat diet (HFD) for 12–16 weeks. HFD-fed DIO mice exhibited decreased ApoER2 and VLDLR expression and increased RELN protein in the hypothalamus. Electrophysiology was used to determine the mechanism by which the central fragment of RELN (CF-RELN) acts on arcuate nucleus (ARH) satiety-promoting proopiomelanocortin (POMC) neurons and the impact of DIO on this circuitry. Results: CF-RELN exhibited heterogeneous presynaptic actions on inhibitory inputs onto ARH-POMC-EGFP neurons and consistent postsynaptic actions. Additionally, central administration of CF-RELN caused a significant increase in ARH c-Fos expression and an acute decrease in food intake and body weight. Conclusions: We conclude that RELN signaling is modulated by diet, that RELN is involved in synaptic signaling onto ARH-POMC neurons, and that altering central CF-RELN levels can impact food intake and body weight.

Original languageEnglish (US)
JournalMolecular Metabolism
DOIs
StatePublished - Jan 1 2019

Fingerprint

Pro-Opiomelanocortin
Obesity
Diet
Neurons
High Fat Diet
Hypothalamus
Eating
Body Weight
Arcuate Nucleus of Hypothalamus
Electrophysiology
Bipolar Disorder
Lipid Metabolism
Synapses
Energy Metabolism
Schizophrenia
Glycoproteins
Psychology
Brain

Keywords

  • Arcuate nucleus
  • Obesity
  • Proopiomelanocortin
  • Reelin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons. / Roberts, Brandon L.; Bennett, Baylin J.; Bennett, Camdin M.; Carroll, Julie M.; Dalbøge, Louise S.; Hall, Colin; Hassouneh, Wafa; Heppner, Kristy M.; Kirigiti, Melissa A.; Lindsley, Sarah R.; Tennant, Katherine G.; True, Cadence A.; Whittle, Andrew; Wolf, Anitra C.; Roberts, Charles; Tang-Christensen, Mads; Sleeman, Mark W.; Cowley, Michael A.; Grove, Kevin; Kievit, Paul.

In: Molecular Metabolism, 01.01.2019.

Research output: Contribution to journalArticle

Roberts, BL, Bennett, BJ, Bennett, CM, Carroll, JM, Dalbøge, LS, Hall, C, Hassouneh, W, Heppner, KM, Kirigiti, MA, Lindsley, SR, Tennant, KG, True, CA, Whittle, A, Wolf, AC, Roberts, C, Tang-Christensen, M, Sleeman, MW, Cowley, MA, Grove, K & Kievit, P 2019, 'Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons', Molecular Metabolism. https://doi.org/10.1016/j.molmet.2019.06.001
Roberts, Brandon L. ; Bennett, Baylin J. ; Bennett, Camdin M. ; Carroll, Julie M. ; Dalbøge, Louise S. ; Hall, Colin ; Hassouneh, Wafa ; Heppner, Kristy M. ; Kirigiti, Melissa A. ; Lindsley, Sarah R. ; Tennant, Katherine G. ; True, Cadence A. ; Whittle, Andrew ; Wolf, Anitra C. ; Roberts, Charles ; Tang-Christensen, Mads ; Sleeman, Mark W. ; Cowley, Michael A. ; Grove, Kevin ; Kievit, Paul. / Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons. In: Molecular Metabolism. 2019.
@article{961e76a064a143ffba052f42d4aa265a,
title = "Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons",
abstract = "Objective: Reelin (RELN) is a large glycoprotein involved in synapse maturation and neuronal organization throughout development. Deficits in RELN signaling contribute to multiple psychological disorders, such as autism spectrum disorder, schizophrenia, and bipolar disorder. Nutritional stress alters RELN expression in brain regions associated with these disorders; however, the involvement of RELN in the neural circuits involved in energy metabolism is unknown. The RELN receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are involved in lipid metabolism and expressed in the hypothalamus. Here we explored the involvement of RELN in hypothalamic signaling and the impact of diet-induced obesity (DIO) on this system. Methods: Adult male mice were fed a chow diet or maintained on a high-fat diet (HFD) for 12–16 weeks. HFD-fed DIO mice exhibited decreased ApoER2 and VLDLR expression and increased RELN protein in the hypothalamus. Electrophysiology was used to determine the mechanism by which the central fragment of RELN (CF-RELN) acts on arcuate nucleus (ARH) satiety-promoting proopiomelanocortin (POMC) neurons and the impact of DIO on this circuitry. Results: CF-RELN exhibited heterogeneous presynaptic actions on inhibitory inputs onto ARH-POMC-EGFP neurons and consistent postsynaptic actions. Additionally, central administration of CF-RELN caused a significant increase in ARH c-Fos expression and an acute decrease in food intake and body weight. Conclusions: We conclude that RELN signaling is modulated by diet, that RELN is involved in synaptic signaling onto ARH-POMC neurons, and that altering central CF-RELN levels can impact food intake and body weight.",
keywords = "Arcuate nucleus, Obesity, Proopiomelanocortin, Reelin",
author = "Roberts, {Brandon L.} and Bennett, {Baylin J.} and Bennett, {Camdin M.} and Carroll, {Julie M.} and Dalb{\o}ge, {Louise S.} and Colin Hall and Wafa Hassouneh and Heppner, {Kristy M.} and Kirigiti, {Melissa A.} and Lindsley, {Sarah R.} and Tennant, {Katherine G.} and True, {Cadence A.} and Andrew Whittle and Wolf, {Anitra C.} and Charles Roberts and Mads Tang-Christensen and Sleeman, {Mark W.} and Cowley, {Michael A.} and Kevin Grove and Paul Kievit",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.molmet.2019.06.001",
language = "English (US)",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier GmbH",

}

TY - JOUR

T1 - Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons

AU - Roberts, Brandon L.

AU - Bennett, Baylin J.

AU - Bennett, Camdin M.

AU - Carroll, Julie M.

AU - Dalbøge, Louise S.

AU - Hall, Colin

AU - Hassouneh, Wafa

AU - Heppner, Kristy M.

AU - Kirigiti, Melissa A.

AU - Lindsley, Sarah R.

AU - Tennant, Katherine G.

AU - True, Cadence A.

AU - Whittle, Andrew

AU - Wolf, Anitra C.

AU - Roberts, Charles

AU - Tang-Christensen, Mads

AU - Sleeman, Mark W.

AU - Cowley, Michael A.

AU - Grove, Kevin

AU - Kievit, Paul

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: Reelin (RELN) is a large glycoprotein involved in synapse maturation and neuronal organization throughout development. Deficits in RELN signaling contribute to multiple psychological disorders, such as autism spectrum disorder, schizophrenia, and bipolar disorder. Nutritional stress alters RELN expression in brain regions associated with these disorders; however, the involvement of RELN in the neural circuits involved in energy metabolism is unknown. The RELN receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are involved in lipid metabolism and expressed in the hypothalamus. Here we explored the involvement of RELN in hypothalamic signaling and the impact of diet-induced obesity (DIO) on this system. Methods: Adult male mice were fed a chow diet or maintained on a high-fat diet (HFD) for 12–16 weeks. HFD-fed DIO mice exhibited decreased ApoER2 and VLDLR expression and increased RELN protein in the hypothalamus. Electrophysiology was used to determine the mechanism by which the central fragment of RELN (CF-RELN) acts on arcuate nucleus (ARH) satiety-promoting proopiomelanocortin (POMC) neurons and the impact of DIO on this circuitry. Results: CF-RELN exhibited heterogeneous presynaptic actions on inhibitory inputs onto ARH-POMC-EGFP neurons and consistent postsynaptic actions. Additionally, central administration of CF-RELN caused a significant increase in ARH c-Fos expression and an acute decrease in food intake and body weight. Conclusions: We conclude that RELN signaling is modulated by diet, that RELN is involved in synaptic signaling onto ARH-POMC neurons, and that altering central CF-RELN levels can impact food intake and body weight.

AB - Objective: Reelin (RELN) is a large glycoprotein involved in synapse maturation and neuronal organization throughout development. Deficits in RELN signaling contribute to multiple psychological disorders, such as autism spectrum disorder, schizophrenia, and bipolar disorder. Nutritional stress alters RELN expression in brain regions associated with these disorders; however, the involvement of RELN in the neural circuits involved in energy metabolism is unknown. The RELN receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are involved in lipid metabolism and expressed in the hypothalamus. Here we explored the involvement of RELN in hypothalamic signaling and the impact of diet-induced obesity (DIO) on this system. Methods: Adult male mice were fed a chow diet or maintained on a high-fat diet (HFD) for 12–16 weeks. HFD-fed DIO mice exhibited decreased ApoER2 and VLDLR expression and increased RELN protein in the hypothalamus. Electrophysiology was used to determine the mechanism by which the central fragment of RELN (CF-RELN) acts on arcuate nucleus (ARH) satiety-promoting proopiomelanocortin (POMC) neurons and the impact of DIO on this circuitry. Results: CF-RELN exhibited heterogeneous presynaptic actions on inhibitory inputs onto ARH-POMC-EGFP neurons and consistent postsynaptic actions. Additionally, central administration of CF-RELN caused a significant increase in ARH c-Fos expression and an acute decrease in food intake and body weight. Conclusions: We conclude that RELN signaling is modulated by diet, that RELN is involved in synaptic signaling onto ARH-POMC neurons, and that altering central CF-RELN levels can impact food intake and body weight.

KW - Arcuate nucleus

KW - Obesity

KW - Proopiomelanocortin

KW - Reelin

UR - http://www.scopus.com/inward/record.url?scp=85067440770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067440770&partnerID=8YFLogxK

U2 - 10.1016/j.molmet.2019.06.001

DO - 10.1016/j.molmet.2019.06.001

M3 - Article

AN - SCOPUS:85067440770

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

ER -