Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice
Hormone-sensitive lipase (HSL) plays a crucial role in intracellular lipolysis, and loss of HSL leads to diacylglycerol (DAG) accumulation, reduced FA mobilization, and impaired PPARγ signaling. Hsl knockout mice exhibit adipose tissue inflammation, but the underlying mechanisms are still not clear....
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227522001389 |
| _version_ | 1797944081373986816 |
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| author | Petra Kotzbeck Ulrike Taschler Christoph Haudum Ines Foessl Gabriele Schoiswohl Beate Boulgaropoulos Kaddour Bounab Johanna Einsiedler Laura Pajed Anna Tilp Anna Schwarz Thomas O. Eichmann Barbara Obermayer-Pietsch Antonio Giordano Saverio Cinti Rudolf Zechner Thomas R. Pieber |
| author_facet | Petra Kotzbeck Ulrike Taschler Christoph Haudum Ines Foessl Gabriele Schoiswohl Beate Boulgaropoulos Kaddour Bounab Johanna Einsiedler Laura Pajed Anna Tilp Anna Schwarz Thomas O. Eichmann Barbara Obermayer-Pietsch Antonio Giordano Saverio Cinti Rudolf Zechner Thomas R. Pieber |
| author_sort | Petra Kotzbeck |
| collection | DOAJ |
| description | Hormone-sensitive lipase (HSL) plays a crucial role in intracellular lipolysis, and loss of HSL leads to diacylglycerol (DAG) accumulation, reduced FA mobilization, and impaired PPARγ signaling. Hsl knockout mice exhibit adipose tissue inflammation, but the underlying mechanisms are still not clear. Here, we investigated if and to what extent HSL loss contributes to endoplasmic reticulum (ER) stress and adipose tissue inflammation in Hsl knockout mice. Furthermore, we were interested in how impaired PPARγ signaling affects the development of inflammation in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) of Hsl knockout mice and if DAG and ceramide accumulation contribute to adipose tissue inflammation and ER stress. Ultrastructural analysis showed a markedly dilated ER in both eWAT and iWAT upon loss of HSL. In addition, Hsl knockout mice exhibited macrophage infiltration and increased F4/80 mRNA expression, a marker of macrophage activation, in eWAT, but not in iWAT. We show that treatment with rosiglitazone, a PPARγ agonist, attenuated macrophage infiltration and ameliorated inflammation of eWAT, but expression of ER stress markers remained unchanged, as did DAG and ceramide levels in eWAT. Taken together, we show that HSL loss promoted ER stress in both eWAT and iWAT of Hsl knockout mice, but inflammation and macrophage infiltration occurred mainly in eWAT. Also, PPARγ activation reversed inflammation but not ER stress and DAG accumulation. These data indicate that neither reduction of DAG levels nor ER stress contribute to the reversal of eWAT inflammation in Hsl knockout mice. |
| first_indexed | 2024-04-10T20:33:59Z |
| format | Article |
| id | doaj.art-80063204e648425484a550a793ab4a26 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-10T20:33:59Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-80063204e648425484a550a793ab4a262023-01-25T04:14:39ZengElsevierJournal of Lipid Research0022-22752023-01-01641100305Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout MicePetra Kotzbeck0Ulrike Taschler1Christoph Haudum2Ines Foessl3Gabriele Schoiswohl4Beate Boulgaropoulos5Kaddour Bounab6Johanna Einsiedler7Laura Pajed8Anna Tilp9Anna Schwarz10Thomas O. Eichmann11Barbara Obermayer-Pietsch12Antonio Giordano13Saverio Cinti14Rudolf Zechner15Thomas R. Pieber16Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria; Institute of Molecular Biosciences, University of Graz, Graz, Austria; Research Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria; Cooperative Centre for Regenerative Medicine (COREMED), Joanneum Research Forschungsgesellschaft m.b.H, Graz, Austria; For correspondence: Petra KotzbeckInstitute of Molecular Biosciences, University of Graz, Graz, AustriaDivision of Endocrinology and Diabetology, Medical University of Graz, Graz, AustriaDivision of Endocrinology and Diabetology, Medical University of Graz, Graz, AustriaDepartment of Pharmacology and Toxicology, University of Graz, Graz, AustriaDivision of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria; Institute for Biomedicine and Health Sciences (HEALTH), Joanneum Research Forschungsgesellschaft m.b.H, Graz, AustriaDivision of Endocrinology and Diabetology, Medical University of Graz, Graz, AustriaDivision of Endocrinology and Diabetology, Medical University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaResearch Unit for Tissue Regeneration, Repair and Reconstruction, Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria; Cooperative Centre for Regenerative Medicine (COREMED), Joanneum Research Forschungsgesellschaft m.b.H, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, Austria; Center for Explorative Lipidomics, BioTechMed-Graz, Graz, AustriaDivision of Endocrinology and Diabetology, Medical University of Graz, Graz, AustriaDepartment of Experimental and Clinical Medicine, Center of Obesity, University of Ancona (Politecnica delle Marche), Ancona, ItalyDepartment of Experimental and Clinical Medicine, Center of Obesity, University of Ancona (Politecnica delle Marche), Ancona, ItalyInstitute of Molecular Biosciences, University of Graz, Graz, Austria; BioTechMed-Graz, Graz, AustriaDivision of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria; Institute for Biomedicine and Health Sciences (HEALTH), Joanneum Research Forschungsgesellschaft m.b.H, Graz, Austria; BioTechMed-Graz, Graz, AustriaHormone-sensitive lipase (HSL) plays a crucial role in intracellular lipolysis, and loss of HSL leads to diacylglycerol (DAG) accumulation, reduced FA mobilization, and impaired PPARγ signaling. Hsl knockout mice exhibit adipose tissue inflammation, but the underlying mechanisms are still not clear. Here, we investigated if and to what extent HSL loss contributes to endoplasmic reticulum (ER) stress and adipose tissue inflammation in Hsl knockout mice. Furthermore, we were interested in how impaired PPARγ signaling affects the development of inflammation in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) of Hsl knockout mice and if DAG and ceramide accumulation contribute to adipose tissue inflammation and ER stress. Ultrastructural analysis showed a markedly dilated ER in both eWAT and iWAT upon loss of HSL. In addition, Hsl knockout mice exhibited macrophage infiltration and increased F4/80 mRNA expression, a marker of macrophage activation, in eWAT, but not in iWAT. We show that treatment with rosiglitazone, a PPARγ agonist, attenuated macrophage infiltration and ameliorated inflammation of eWAT, but expression of ER stress markers remained unchanged, as did DAG and ceramide levels in eWAT. Taken together, we show that HSL loss promoted ER stress in both eWAT and iWAT of Hsl knockout mice, but inflammation and macrophage infiltration occurred mainly in eWAT. Also, PPARγ activation reversed inflammation but not ER stress and DAG accumulation. These data indicate that neither reduction of DAG levels nor ER stress contribute to the reversal of eWAT inflammation in Hsl knockout mice.http://www.sciencedirect.com/science/article/pii/S0022227522001389adipocytesadipose tissuelipolysisFA metabolismlipaseinflammation |
| spellingShingle | Petra Kotzbeck Ulrike Taschler Christoph Haudum Ines Foessl Gabriele Schoiswohl Beate Boulgaropoulos Kaddour Bounab Johanna Einsiedler Laura Pajed Anna Tilp Anna Schwarz Thomas O. Eichmann Barbara Obermayer-Pietsch Antonio Giordano Saverio Cinti Rudolf Zechner Thomas R. Pieber Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice Journal of Lipid Research adipocytes adipose tissue lipolysis FA metabolism lipase inflammation |
| title | Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice |
| title_full | Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice |
| title_fullStr | Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice |
| title_full_unstemmed | Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice |
| title_short | Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice |
| title_sort | rosiglitazone reverses inflammation in epididymal white adipose tissue in hormone sensitive lipase knockout mice |
| topic | adipocytes adipose tissue lipolysis FA metabolism lipase inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0022227522001389 |
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