Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity
Consumption of a hypercaloric diet upregulates microglial innate immune reactivity along with a higher expression of lipoprotein lipase (Lpl) within the reactive microglia in the mouse brain. Here, we show that knockdown of the Lpl gene specifically in microglia resulted in deficient microglial upta...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471731269X |
| _version_ | 1819070236205252608 |
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| author | Yuanqing Gao Andrés Vidal-Itriago Martin J. Kalsbeek Clarita Layritz Cristina García-Cáceres Robby Zachariah Tom Thomas O. Eichmann Frédéric M. Vaz Riekelt H. Houtkooper Nicole van der Wel Arthur J. Verhoeven Jie Yan Andries Kalsbeek Robert H. Eckel Susanna M. Hofmann Chun-Xia Yi |
| author_facet | Yuanqing Gao Andrés Vidal-Itriago Martin J. Kalsbeek Clarita Layritz Cristina García-Cáceres Robby Zachariah Tom Thomas O. Eichmann Frédéric M. Vaz Riekelt H. Houtkooper Nicole van der Wel Arthur J. Verhoeven Jie Yan Andries Kalsbeek Robert H. Eckel Susanna M. Hofmann Chun-Xia Yi |
| author_sort | Yuanqing Gao |
| collection | DOAJ |
| description | Consumption of a hypercaloric diet upregulates microglial innate immune reactivity along with a higher expression of lipoprotein lipase (Lpl) within the reactive microglia in the mouse brain. Here, we show that knockdown of the Lpl gene specifically in microglia resulted in deficient microglial uptake of lipid, mitochondrial fuel utilization shifting to glutamine, and significantly decreased immune reactivity. Mice with knockdown of the Lpl gene in microglia gained more body weight than control mice on a high-carbohydrate high-fat (HCHF) diet. In these mice, microglial reactivity was significantly decreased in the mediobasal hypothalamus, accompanied by downregulation of phagocytic capacity and increased mitochondrial dysmorphologies. Furthermore, HCHF-diet-induced POMC neuronal loss was accelerated. These results show that LPL-governed microglial immunometabolism is essential to maintain microglial function upon exposure to an HCHF diet. In a hypercaloric environment, lack of such an adaptive immunometabolic response has detrimental effects on CNS regulation of energy metabolism. |
| first_indexed | 2024-12-21T17:02:43Z |
| format | Article |
| id | doaj.art-278d3dbbc28e4d3894db4c7ece5dd2ca |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T17:02:43Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-278d3dbbc28e4d3894db4c7ece5dd2ca2022-12-21T18:56:36ZengElsevierCell Reports2211-12472017-09-0120133034304210.1016/j.celrep.2017.09.008Lipoprotein Lipase Maintains Microglial Innate Immunity in ObesityYuanqing Gao0Andrés Vidal-Itriago1Martin J. Kalsbeek2Clarita Layritz3Cristina García-Cáceres4Robby Zachariah Tom5Thomas O. Eichmann6Frédéric M. Vaz7Riekelt H. Houtkooper8Nicole van der Wel9Arthur J. Verhoeven10Jie Yan11Andries Kalsbeek12Robert H. Eckel13Susanna M. Hofmann14Chun-Xia Yi15Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, the NetherlandsDepartment of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, the NetherlandsDepartment of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, the NetherlandsHelmholtz Diabetes Center & German Center for Diabetes Research, Helmholtz Zentrum München & Division of Metabolic Diseases, Technische Universität München, Munich, GermanyHelmholtz Diabetes Center & German Center for Diabetes Research, Helmholtz Zentrum München & Division of Metabolic Diseases, Technische Universität München, Munich, GermanyInstitute for Diabetes and Regeneration Research & Helmholtz Diabetes Center, Helmholtz Zentrum München, Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, GermanyInstitute of Molecular Biosciences, University of Graz, AustriaLaboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, the NetherlandsLaboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, the NetherlandsCellular Imaging Core Facility, Academic Medical Center, University of Amsterdam, the NetherlandsDepartment of Medical Biochemistry, Academic Medical Centre, University of Amsterdam, the NetherlandsDepartment of Forensic Science, School of Basic Medical Science, Central South University, Changsha, Hunan, ChinaDepartment of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, the NetherlandsDivision of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora, CO, USAInstitute for Diabetes and Regeneration Research & Helmholtz Diabetes Center, Helmholtz Zentrum München, Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, GermanyDepartment of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, the NetherlandsConsumption of a hypercaloric diet upregulates microglial innate immune reactivity along with a higher expression of lipoprotein lipase (Lpl) within the reactive microglia in the mouse brain. Here, we show that knockdown of the Lpl gene specifically in microglia resulted in deficient microglial uptake of lipid, mitochondrial fuel utilization shifting to glutamine, and significantly decreased immune reactivity. Mice with knockdown of the Lpl gene in microglia gained more body weight than control mice on a high-carbohydrate high-fat (HCHF) diet. In these mice, microglial reactivity was significantly decreased in the mediobasal hypothalamus, accompanied by downregulation of phagocytic capacity and increased mitochondrial dysmorphologies. Furthermore, HCHF-diet-induced POMC neuronal loss was accelerated. These results show that LPL-governed microglial immunometabolism is essential to maintain microglial function upon exposure to an HCHF diet. In a hypercaloric environment, lack of such an adaptive immunometabolic response has detrimental effects on CNS regulation of energy metabolism.http://www.sciencedirect.com/science/article/pii/S221112471731269Xhypothalamusvery low-density lipoproteinphagocytosisphospholipidmitochondriafuel dependencyglutamineTNF-αNF-κBautophagosomes |
| spellingShingle | Yuanqing Gao Andrés Vidal-Itriago Martin J. Kalsbeek Clarita Layritz Cristina García-Cáceres Robby Zachariah Tom Thomas O. Eichmann Frédéric M. Vaz Riekelt H. Houtkooper Nicole van der Wel Arthur J. Verhoeven Jie Yan Andries Kalsbeek Robert H. Eckel Susanna M. Hofmann Chun-Xia Yi Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity Cell Reports hypothalamus very low-density lipoprotein phagocytosis phospholipid mitochondria fuel dependency glutamine TNF-α NF-κB autophagosomes |
| title | Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity |
| title_full | Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity |
| title_fullStr | Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity |
| title_full_unstemmed | Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity |
| title_short | Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity |
| title_sort | lipoprotein lipase maintains microglial innate immunity in obesity |
| topic | hypothalamus very low-density lipoprotein phagocytosis phospholipid mitochondria fuel dependency glutamine TNF-α NF-κB autophagosomes |
| url | http://www.sciencedirect.com/science/article/pii/S221112471731269X |
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