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Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells

OBJECTIVE: Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypo...

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Autores principales: Jeon, Songhee, Park, Jeong-Eun, Do, Young Ho, Santos, Renata, Lee, Seong Mi, Kim, Bung-Nyun, Cheong, Jae Hoon, Kim, Yeni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Neuropsychiatric Association 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064201/
https://www.ncbi.nlm.nih.gov/pubmed/36990664
http://dx.doi.org/10.30773/pi.2022.0255
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author Jeon, Songhee
Park, Jeong-Eun
Do, Young Ho
Santos, Renata
Lee, Seong Mi
Kim, Bung-Nyun
Cheong, Jae Hoon
Kim, Yeni
author_facet Jeon, Songhee
Park, Jeong-Eun
Do, Young Ho
Santos, Renata
Lee, Seong Mi
Kim, Bung-Nyun
Cheong, Jae Hoon
Kim, Yeni
author_sort Jeon, Songhee
collection PubMed
description OBJECTIVE: Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus. METHODS: Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures. RESULTS: Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30–60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKβ inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKβ phosphorylation. CONCLUSION: These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKβ in human SH-SY5Y and U-87 MG cells.
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spelling pubmed-100642012023-04-01 Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells Jeon, Songhee Park, Jeong-Eun Do, Young Ho Santos, Renata Lee, Seong Mi Kim, Bung-Nyun Cheong, Jae Hoon Kim, Yeni Psychiatry Investig Original Article OBJECTIVE: Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus. METHODS: Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures. RESULTS: Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30–60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKβ inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKβ phosphorylation. CONCLUSION: These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKβ in human SH-SY5Y and U-87 MG cells. Korean Neuropsychiatric Association 2023-03 2023-03-22 /pmc/articles/PMC10064201/ /pubmed/36990664 http://dx.doi.org/10.30773/pi.2022.0255 Text en Copyright © 2023 Korean Neuropsychiatric Association https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Jeon, Songhee
Park, Jeong-Eun
Do, Young Ho
Santos, Renata
Lee, Seong Mi
Kim, Bung-Nyun
Cheong, Jae Hoon
Kim, Yeni
Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells
title Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells
title_full Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells
title_fullStr Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells
title_full_unstemmed Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells
title_short Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells
title_sort atomoxetine and fluoxetine activate ampk-acc-cpt1 pathway in human sh-sy5y and u-87 mg cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064201/
https://www.ncbi.nlm.nih.gov/pubmed/36990664
http://dx.doi.org/10.30773/pi.2022.0255
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