Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions

The adipose tissue stores excess energy in the form of neutral lipids within adipocyte lipid droplets (LDs). The correct function of LDs requires the interaction with other organelles, such as the endoplasmic reticulum (ER) as well as with LD coat-associated proteins, including Rab18, a mediator of...

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Main Authors: Jaime López-Alcalá, M. Carmen Soler-Vázquez, Carmen Tercero-Alcázar, Julia Sánchez-Ceinos, Rocío Guzmán-Ruiz, María M. Malagón, Ana Gordon
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/24/17177
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author Jaime López-Alcalá
M. Carmen Soler-Vázquez
Carmen Tercero-Alcázar
Julia Sánchez-Ceinos
Rocío Guzmán-Ruiz
María M. Malagón
Ana Gordon
author_facet Jaime López-Alcalá
M. Carmen Soler-Vázquez
Carmen Tercero-Alcázar
Julia Sánchez-Ceinos
Rocío Guzmán-Ruiz
María M. Malagón
Ana Gordon
author_sort Jaime López-Alcalá
collection DOAJ
description The adipose tissue stores excess energy in the form of neutral lipids within adipocyte lipid droplets (LDs). The correct function of LDs requires the interaction with other organelles, such as the endoplasmic reticulum (ER) as well as with LD coat-associated proteins, including Rab18, a mediator of intracellular lipid trafficking and ER–LD interaction. Although perturbations of the inter-organelle contact sites have been linked to several diseases, such as cancer, no information regarding ER–LD contact sites in dysfunctional adipocytes from the obese adipose tissue has been published to date. Herein, the ER–LD connection and Rab18 distribution at ER–LD contact sites are examined in adipocytes challenged with fibrosis and inflammatory conditions, which represent known hallmarks of the adipose tissue in obesity. Our results show that adipocytes differentiated in fibrotic conditions caused ER fragmentation, the expansion of ER–LD contact sites, and modified Rab18 dynamics. Likewise, adipocytes exposed to inflammatory conditions favored ER–LD contact, Rab18 accumulation in the ER, and Rab18 redistribution to large LDs. Finally, our studies in human adipocytes supported the suggestion that Rab18 transitions to the LD coat from the ER. Taken together, our results suggest that obesity-related pathogenic processes alter the maintenance of ER–LD interactions and interfere with Rab18 trafficking through these contact sites.
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spelling doaj.art-7bafbd9df23e4c17b29cb743a01557572023-12-22T14:13:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241717710.3390/ijms242417177Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic ConditionsJaime López-Alcalá0M. Carmen Soler-Vázquez1Carmen Tercero-Alcázar2Julia Sánchez-Ceinos3Rocío Guzmán-Ruiz4María M. Malagón5Ana Gordon6Department of Cell Biology, Physiology, and Immunology, Adipobiology Group, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, SpainDepartment of Cell Biology, Physiology, and Immunology, Adipobiology Group, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, SpainDepartment of Cell Biology, Physiology, and Immunology, Adipobiology Group, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, SpainCardiology Unit, Department of Medicine-Solna, Karolinska Institute (KI), Karolinska University Hospital (NKS), 17177 Stockholm, SwedenDepartment of Cell Biology, Physiology, and Immunology, Adipobiology Group, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, SpainDepartment of Cell Biology, Physiology, and Immunology, Adipobiology Group, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, SpainDepartment of Cell Biology, Physiology, and Immunology, Adipobiology Group, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, SpainThe adipose tissue stores excess energy in the form of neutral lipids within adipocyte lipid droplets (LDs). The correct function of LDs requires the interaction with other organelles, such as the endoplasmic reticulum (ER) as well as with LD coat-associated proteins, including Rab18, a mediator of intracellular lipid trafficking and ER–LD interaction. Although perturbations of the inter-organelle contact sites have been linked to several diseases, such as cancer, no information regarding ER–LD contact sites in dysfunctional adipocytes from the obese adipose tissue has been published to date. Herein, the ER–LD connection and Rab18 distribution at ER–LD contact sites are examined in adipocytes challenged with fibrosis and inflammatory conditions, which represent known hallmarks of the adipose tissue in obesity. Our results show that adipocytes differentiated in fibrotic conditions caused ER fragmentation, the expansion of ER–LD contact sites, and modified Rab18 dynamics. Likewise, adipocytes exposed to inflammatory conditions favored ER–LD contact, Rab18 accumulation in the ER, and Rab18 redistribution to large LDs. Finally, our studies in human adipocytes supported the suggestion that Rab18 transitions to the LD coat from the ER. Taken together, our results suggest that obesity-related pathogenic processes alter the maintenance of ER–LD interactions and interfere with Rab18 trafficking through these contact sites.https://www.mdpi.com/1422-0067/24/24/17177adipocyteendoplasmic reticulumlipid dropletRab18fibrosisinflammation
spellingShingle Jaime López-Alcalá
M. Carmen Soler-Vázquez
Carmen Tercero-Alcázar
Julia Sánchez-Ceinos
Rocío Guzmán-Ruiz
María M. Malagón
Ana Gordon
Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions
International Journal of Molecular Sciences
adipocyte
endoplasmic reticulum
lipid droplet
Rab18
fibrosis
inflammation
title Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions
title_full Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions
title_fullStr Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions
title_full_unstemmed Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions
title_short Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions
title_sort rab18 drift in lipid droplet and endoplasmic reticulum interactions of adipocytes under obesogenic conditions
topic adipocyte
endoplasmic reticulum
lipid droplet
Rab18
fibrosis
inflammation
url https://www.mdpi.com/1422-0067/24/24/17177
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