<i>Slc7a8</i> Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs

Adipogenesis, through adipocyte hyperplasia and/or hypertrophy, leads to increased adiposity, giving rise to obesity. A genome-wide transcriptome analysis of in vitro adipogenesis in human adipose-derived stromal/stem cells identified SLC7A8 (Solute Carrier Family 7 Member 8) as a potential novel me...

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Main Authors: Reabetswe R. Pitere, Marlene B. van Heerden, Michael S. Pepper, Melvin A. Ambele
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/11/2/311
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author Reabetswe R. Pitere
Marlene B. van Heerden
Michael S. Pepper
Melvin A. Ambele
author_facet Reabetswe R. Pitere
Marlene B. van Heerden
Michael S. Pepper
Melvin A. Ambele
author_sort Reabetswe R. Pitere
collection DOAJ
description Adipogenesis, through adipocyte hyperplasia and/or hypertrophy, leads to increased adiposity, giving rise to obesity. A genome-wide transcriptome analysis of in vitro adipogenesis in human adipose-derived stromal/stem cells identified SLC7A8 (Solute Carrier Family 7 Member 8) as a potential novel mediator. The current study has investigated the role of SLC7A8 in adipose tissue biology using a mouse model of diet-induced obesity. <i>slc7a8</i> knockout (KO) and wildtype (WT) C57BL/6J mice were fed either a control diet (CD) or a high-fat diet (HFD) for 14 weeks. On the HFD, both WT and KO mice (WTHFD and KOHFD) gained significantly more weight than their CD counterparts. However, KOHFD gained significantly less weight than WTHFD. KOHFD had significantly reduced levels of glucose intolerance compared with those observed in WTHFD. KOHFD also had significantly reduced adipocyte mass and hypertrophy in inguinal, mesenteric, perigonadal, and brown adipose depots, with a corresponding decrease in macrophage infiltration. Additionally, KOHFD had decreased lipid accumulation in the liver, heart, gastrocnemius muscle, lung, and kidney. This study demonstrates that targeting <i>slc7a8</i> protects against diet-induced obesity by reducing lipid accumulation in multiple organs and suggests that if targeted, has the potential to mitigate the development of obesity-associated comorbidities.
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spelling doaj.art-c5ae7a412d4f4c2484013331f387920d2023-11-23T18:51:16ZengMDPI AGBiology2079-77372022-02-0111231110.3390/biology11020311<i>Slc7a8</i> Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple OrgansReabetswe R. Pitere0Marlene B. van Heerden1Michael S. Pepper2Melvin A. Ambele3Institute for Cellular and Molecular Medicine, Department of Immunology and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaDepartment of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaInstitute for Cellular and Molecular Medicine, Department of Immunology and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaInstitute for Cellular and Molecular Medicine, Department of Immunology and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South AfricaAdipogenesis, through adipocyte hyperplasia and/or hypertrophy, leads to increased adiposity, giving rise to obesity. A genome-wide transcriptome analysis of in vitro adipogenesis in human adipose-derived stromal/stem cells identified SLC7A8 (Solute Carrier Family 7 Member 8) as a potential novel mediator. The current study has investigated the role of SLC7A8 in adipose tissue biology using a mouse model of diet-induced obesity. <i>slc7a8</i> knockout (KO) and wildtype (WT) C57BL/6J mice were fed either a control diet (CD) or a high-fat diet (HFD) for 14 weeks. On the HFD, both WT and KO mice (WTHFD and KOHFD) gained significantly more weight than their CD counterparts. However, KOHFD gained significantly less weight than WTHFD. KOHFD had significantly reduced levels of glucose intolerance compared with those observed in WTHFD. KOHFD also had significantly reduced adipocyte mass and hypertrophy in inguinal, mesenteric, perigonadal, and brown adipose depots, with a corresponding decrease in macrophage infiltration. Additionally, KOHFD had decreased lipid accumulation in the liver, heart, gastrocnemius muscle, lung, and kidney. This study demonstrates that targeting <i>slc7a8</i> protects against diet-induced obesity by reducing lipid accumulation in multiple organs and suggests that if targeted, has the potential to mitigate the development of obesity-associated comorbidities.https://www.mdpi.com/2079-7737/11/2/311obesityadipose tissueadipogenesislipid accumulationSLC7A8fat depots
spellingShingle Reabetswe R. Pitere
Marlene B. van Heerden
Michael S. Pepper
Melvin A. Ambele
<i>Slc7a8</i> Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs
Biology
obesity
adipose tissue
adipogenesis
lipid accumulation
SLC7A8
fat depots
title <i>Slc7a8</i> Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs
title_full <i>Slc7a8</i> Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs
title_fullStr <i>Slc7a8</i> Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs
title_full_unstemmed <i>Slc7a8</i> Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs
title_short <i>Slc7a8</i> Deletion Is Protective against Diet-Induced Obesity and Attenuates Lipid Accumulation in Multiple Organs
title_sort i slc7a8 i deletion is protective against diet induced obesity and attenuates lipid accumulation in multiple organs
topic obesity
adipose tissue
adipogenesis
lipid accumulation
SLC7A8
fat depots
url https://www.mdpi.com/2079-7737/11/2/311
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AT michaelspepper islc7a8ideletionisprotectiveagainstdietinducedobesityandattenuateslipidaccumulationinmultipleorgans
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