Palmitic Acid Modulation of the Insulin-Like Growth Factor System in Hypothalamic Astrocytes and Neurons

Santiago Guerra-Cantera; Laura M. Frago; Yesenia Espinoza-Chavarria; Roberto Collado-Pérez; María Jiménez-Hernaiz; Marta Torrecilla-Parra; Vicente Barrios; Denise D. Belsham; Lisbeth S. Laursen; Claus Oxvig; Jesús Argente; Julie A. Chowen

doi:10.1159/000540442

Palmitic Acid Modulation of the Insulin-Like Growth Factor System in Hypothalamic Astrocytes and Neurons

Santiago Guerra-Cantera, Laura M. Frago, Yesenia Espinoza-Chavarria, Roberto Collado-Pérez, María Jiménez-Hernaiz, Marta Torrecilla-Parra, Vicente Barrios, Denise D. Belsham, Lisbeth S. Laursen, Claus Oxvig, Jesús Argente^*, Julie A. Chowen^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

Abstract

Introduction: Insulin-like growth factor (IGF)1 and IGF2 have neuroprotective effects, but less is known regarding how other members of the IGF system, including IGF binding proteins (IGFBPs) and the regulatory proteinase pappalysin- 1 (PAPP-A) and its endogenous inhibitor stanniocalcin-2 (STC2) participate in this process. Here, we analyzed whether these members of the IGF system are modified in neurons and astrocytes in response to palmitic acid (PA), a fatty acid that induces cell stress when increased centrally. Methods: Primary hypothalamic astrocyte cultures from male and female PND2 rats and the pro-opiomelanocortin (POMC) neuronal cell line, mHypoA-POMC/GFP-2, were treated with PA, IGF1 or both. To analyze the role of STC2 in astrocytes, siRNA assays were employed. Results: In astrocytes of both sexes, PA rapidly increased cell stress factors followed by increased Pappa and Stc2 mRNA levels and then a decrease in Igf1, Igf2, and Igfbp2 expression and cell number. Exogenous IGF1 did not revert these effects. In mHypoA-POMC/GFP-2 neurons, PA reduced cell number and Pomc and Igf1 mRNA levels, and increased Igfbp2 and Stc2, again with no effect of exogenous IGF1. PA increased STC2 expression, but no effects of decreasing its levels by interference assays or exogenous STC2 treatment in astrocytes were found. Conclusions: The response of the IGF system to PA was cell and sex specific, but no protective effects of the IGFs were found. However, the modifications in hypothalamic PAPP-A and STC2 indicate that further studies are required to determine their role in the response to fatty acids and possibly in metabolic control.

Original language	English
Journal	Neuroendocrinology
Volume	114
Issue	10
Pages (from-to)	958-974
Number of pages	17
ISSN	0028-3835
DOIs	https://doi.org/10.1159/000540442
Publication status	Published - Oct 2024

Keywords

Astrocytes
IGF1
Neuroprotection
Palmitic acid
Stanniocalcin-2

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10.1159/000540442

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Guerra-Cantera, S., Frago, L. M., Espinoza-Chavarria, Y., Collado-Pérez, R., Jiménez-Hernaiz, M., Torrecilla-Parra, M., Barrios, V., Belsham, D. D., Laursen, L. S., Oxvig, C., Argente, J., & Chowen, J. A. (2024). Palmitic Acid Modulation of the Insulin-Like Growth Factor System in Hypothalamic Astrocytes and Neurons. Neuroendocrinology, 114(10), 958-974. https://doi.org/10.1159/000540442

@article{ca54b59003ed428cb60bd33d639eb2ee,

title = "Palmitic Acid Modulation of the Insulin-Like Growth Factor System in Hypothalamic Astrocytes and Neurons",

abstract = "Introduction: Insulin-like growth factor (IGF)1 and IGF2 have neuroprotective effects, but less is known regarding how other members of the IGF system, including IGF binding proteins (IGFBPs) and the regulatory proteinase pappalysin- 1 (PAPP-A) and its endogenous inhibitor stanniocalcin-2 (STC2) participate in this process. Here, we analyzed whether these members of the IGF system are modified in neurons and astrocytes in response to palmitic acid (PA), a fatty acid that induces cell stress when increased centrally. Methods: Primary hypothalamic astrocyte cultures from male and female PND2 rats and the pro-opiomelanocortin (POMC) neuronal cell line, mHypoA-POMC/GFP-2, were treated with PA, IGF1 or both. To analyze the role of STC2 in astrocytes, siRNA assays were employed. Results: In astrocytes of both sexes, PA rapidly increased cell stress factors followed by increased Pappa and Stc2 mRNA levels and then a decrease in Igf1, Igf2, and Igfbp2 expression and cell number. Exogenous IGF1 did not revert these effects. In mHypoA-POMC/GFP-2 neurons, PA reduced cell number and Pomc and Igf1 mRNA levels, and increased Igfbp2 and Stc2, again with no effect of exogenous IGF1. PA increased STC2 expression, but no effects of decreasing its levels by interference assays or exogenous STC2 treatment in astrocytes were found. Conclusions: The response of the IGF system to PA was cell and sex specific, but no protective effects of the IGFs were found. However, the modifications in hypothalamic PAPP-A and STC2 indicate that further studies are required to determine their role in the response to fatty acids and possibly in metabolic control.",

keywords = "Astrocytes, IGF1, Neuroprotection, Palmitic acid, Stanniocalcin-2",

author = "Santiago Guerra-Cantera and Frago, {Laura M.} and Yesenia Espinoza-Chavarria and Roberto Collado-P{\'e}rez and Mar{\'i}a Jim{\'e}nez-Hernaiz and Marta Torrecilla-Parra and Vicente Barrios and Belsham, {Denise D.} and Laursen, {Lisbeth S.} and Claus Oxvig and Jes{\'u}s Argente and Chowen, {Julie A.}",

note = "Publisher Copyright: {\textcopyright} 2024 S. Karger AG, Basel.",

year = "2024",

month = oct,

doi = "10.1159/000540442",

language = "English",

volume = "114",

pages = "958--974",

journal = "Neuroendocrinology",

issn = "0028-3835",

publisher = "S. Karger AG",

number = "10",

}

Guerra-Cantera, S, Frago, LM, Espinoza-Chavarria, Y, Collado-Pérez, R, Jiménez-Hernaiz, M, Torrecilla-Parra, M, Barrios, V, Belsham, DD, Laursen, LS , Oxvig, C, Argente, J & Chowen, JA 2024, 'Palmitic Acid Modulation of the Insulin-Like Growth Factor System in Hypothalamic Astrocytes and Neurons', Neuroendocrinology, vol. 114, no. 10, pp. 958-974. https://doi.org/10.1159/000540442

Palmitic Acid Modulation of the Insulin-Like Growth Factor System in Hypothalamic Astrocytes and Neurons. / Guerra-Cantera, Santiago; Frago, Laura M.; Espinoza-Chavarria, Yesenia et al.
In: Neuroendocrinology, Vol. 114, No. 10, 10.2024, p. 958-974.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Palmitic Acid Modulation of the Insulin-Like Growth Factor System in Hypothalamic Astrocytes and Neurons

AU - Guerra-Cantera, Santiago

AU - Frago, Laura M.

AU - Espinoza-Chavarria, Yesenia

AU - Collado-Pérez, Roberto

AU - Jiménez-Hernaiz, María

AU - Torrecilla-Parra, Marta

AU - Barrios, Vicente

AU - Belsham, Denise D.

AU - Laursen, Lisbeth S.

AU - Oxvig, Claus

AU - Argente, Jesús

AU - Chowen, Julie A.

PY - 2024/10

Y1 - 2024/10

N2 - Introduction: Insulin-like growth factor (IGF)1 and IGF2 have neuroprotective effects, but less is known regarding how other members of the IGF system, including IGF binding proteins (IGFBPs) and the regulatory proteinase pappalysin- 1 (PAPP-A) and its endogenous inhibitor stanniocalcin-2 (STC2) participate in this process. Here, we analyzed whether these members of the IGF system are modified in neurons and astrocytes in response to palmitic acid (PA), a fatty acid that induces cell stress when increased centrally. Methods: Primary hypothalamic astrocyte cultures from male and female PND2 rats and the pro-opiomelanocortin (POMC) neuronal cell line, mHypoA-POMC/GFP-2, were treated with PA, IGF1 or both. To analyze the role of STC2 in astrocytes, siRNA assays were employed. Results: In astrocytes of both sexes, PA rapidly increased cell stress factors followed by increased Pappa and Stc2 mRNA levels and then a decrease in Igf1, Igf2, and Igfbp2 expression and cell number. Exogenous IGF1 did not revert these effects. In mHypoA-POMC/GFP-2 neurons, PA reduced cell number and Pomc and Igf1 mRNA levels, and increased Igfbp2 and Stc2, again with no effect of exogenous IGF1. PA increased STC2 expression, but no effects of decreasing its levels by interference assays or exogenous STC2 treatment in astrocytes were found. Conclusions: The response of the IGF system to PA was cell and sex specific, but no protective effects of the IGFs were found. However, the modifications in hypothalamic PAPP-A and STC2 indicate that further studies are required to determine their role in the response to fatty acids and possibly in metabolic control.

AB - Introduction: Insulin-like growth factor (IGF)1 and IGF2 have neuroprotective effects, but less is known regarding how other members of the IGF system, including IGF binding proteins (IGFBPs) and the regulatory proteinase pappalysin- 1 (PAPP-A) and its endogenous inhibitor stanniocalcin-2 (STC2) participate in this process. Here, we analyzed whether these members of the IGF system are modified in neurons and astrocytes in response to palmitic acid (PA), a fatty acid that induces cell stress when increased centrally. Methods: Primary hypothalamic astrocyte cultures from male and female PND2 rats and the pro-opiomelanocortin (POMC) neuronal cell line, mHypoA-POMC/GFP-2, were treated with PA, IGF1 or both. To analyze the role of STC2 in astrocytes, siRNA assays were employed. Results: In astrocytes of both sexes, PA rapidly increased cell stress factors followed by increased Pappa and Stc2 mRNA levels and then a decrease in Igf1, Igf2, and Igfbp2 expression and cell number. Exogenous IGF1 did not revert these effects. In mHypoA-POMC/GFP-2 neurons, PA reduced cell number and Pomc and Igf1 mRNA levels, and increased Igfbp2 and Stc2, again with no effect of exogenous IGF1. PA increased STC2 expression, but no effects of decreasing its levels by interference assays or exogenous STC2 treatment in astrocytes were found. Conclusions: The response of the IGF system to PA was cell and sex specific, but no protective effects of the IGFs were found. However, the modifications in hypothalamic PAPP-A and STC2 indicate that further studies are required to determine their role in the response to fatty acids and possibly in metabolic control.

KW - Astrocytes

KW - IGF1

KW - Neuroprotection

KW - Palmitic acid

KW - Stanniocalcin-2

UR - http://www.scopus.com/inward/record.url?scp=85203243874&partnerID=8YFLogxK

U2 - 10.1159/000540442

DO - 10.1159/000540442

M3 - Journal article

C2 - 39043147

AN - SCOPUS:85203243874

SN - 0028-3835

VL - 114

SP - 958

EP - 974

JO - Neuroendocrinology

JF - Neuroendocrinology

IS - 10

ER -

Palmitic Acid Modulation of the Insulin-Like Growth Factor System in Hypothalamic Astrocytes and Neurons

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