Circulating HDL levels control hypothalamic astrogliosis via apoA-I
Meta-inflammation of hypothalamic areas governing energy homeostasis has recently emerged as a process of potential pathophysiological relevance for the development of obesity and its metabolic sequelae. The current model suggests that diet-induced neuronal injury triggers microgliosis and astrocyto...
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doaj-e48b521b49e04043b963b66df01ecbce2021-05-03T10:24:32ZengElsevierJournal of Lipid Research0022-22752018-09-0159916491659Circulating HDL levels control hypothalamic astrogliosis via apoA-IAnna Götz0Maarit Lehti1Elizabeth Donelan2Cynthia Striese3Sebastian Cucuruz4Stephan Sachs5Chun-Xia Yi6Stephen C. Woods7Samuel D. Wright8Timo D. Müller9Matthias H. Tschöp10Yuanqing Gao11Susanna M. Hofmann12Institutes for Diabetes and Obesity Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; Department of Internal Medicine I, University Hospital RWTH Aachen, Aachen, GermanyLIKES Research Centre for Physical Activity and Health, Jyväskylä, FinlandMetabolic Disease Institute, Department of Internal Medicine, University of Cincinnati, Cincinnati, OHDiabetes and Regeneration Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, GermanyDiabetes and Regeneration Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, GermanyDiabetes and Regeneration Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, GermanyDepartment of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsMetabolic Disease Institute, Department of Internal Medicine, University of Cincinnati, Cincinnati, OHCSL Behring, King of Prussia, PAInstitutes for Diabetes and Obesity Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, GermanyInstitutes for Diabetes and Obesity Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, GermanyTo whom correspondence should be addressed.; Nanjing Medical University, College of Pharmacy, Nanjing, ChinaTo whom correspondence should be addressed.; German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig Maximilian Universität, Munich, GermanyMeta-inflammation of hypothalamic areas governing energy homeostasis has recently emerged as a process of potential pathophysiological relevance for the development of obesity and its metabolic sequelae. The current model suggests that diet-induced neuronal injury triggers microgliosis and astrocytosis, conditions which ultimately may induce functional impairment of hypothalamic circuits governing feeding behavior, systemic metabolism, and body weight. Epidemiological data indicate that low circulating HDL levels, besides conveying cardiovascular risk, also correlate strongly with obesity. We simulated that condition by using a genetic loss of function mouse model (apoA-I−/−) with markedly reduced HDL levels to investigate whether HDL may directly modulate hypothalamic inflammation. Astrogliosis was significantly enhanced in the hypothalami of apoA-I−/− compared with apoA-I+/+ mice and was associated with compromised mitochondrial function. apoA-I−/− mice exhibited key components of metabolic disease, like increased fat mass, fasting glucose levels, hepatic triglyceride content, and hepatic glucose output compared with apoA-I+/+ controls. Administration of reconstituted HDL (CSL-111) normalized hypothalamic inflammation and mitochondrial function markers in apoA-I−/− mice. Treatment of primary astrocytes with apoA-I resulted in enhanced mitochondrial activity, implying that circulating HDL levels are likely important for astrocyte function. HDL-based therapies may consequently avert reactive gliosis in hypothalamic astrocytes by improving mitochondrial bioenergetics and thereby offering potential treatment and prevention for obesity and metabolic disease.http://www.sciencedirect.com/science/article/pii/S0022227520335343mitochondriainflammationhigh density lipoproteinapolipoprotein A-Imetabolismdyslipidemia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Götz Maarit Lehti Elizabeth Donelan Cynthia Striese Sebastian Cucuruz Stephan Sachs Chun-Xia Yi Stephen C. Woods Samuel D. Wright Timo D. Müller Matthias H. Tschöp Yuanqing Gao Susanna M. Hofmann |
spellingShingle |
Anna Götz Maarit Lehti Elizabeth Donelan Cynthia Striese Sebastian Cucuruz Stephan Sachs Chun-Xia Yi Stephen C. Woods Samuel D. Wright Timo D. Müller Matthias H. Tschöp Yuanqing Gao Susanna M. Hofmann Circulating HDL levels control hypothalamic astrogliosis via apoA-I Journal of Lipid Research mitochondria inflammation high density lipoprotein apolipoprotein A-I metabolism dyslipidemia |
author_facet |
Anna Götz Maarit Lehti Elizabeth Donelan Cynthia Striese Sebastian Cucuruz Stephan Sachs Chun-Xia Yi Stephen C. Woods Samuel D. Wright Timo D. Müller Matthias H. Tschöp Yuanqing Gao Susanna M. Hofmann |
author_sort |
Anna Götz |
title |
Circulating HDL levels control hypothalamic astrogliosis via apoA-I |
title_short |
Circulating HDL levels control hypothalamic astrogliosis via apoA-I |
title_full |
Circulating HDL levels control hypothalamic astrogliosis via apoA-I |
title_fullStr |
Circulating HDL levels control hypothalamic astrogliosis via apoA-I |
title_full_unstemmed |
Circulating HDL levels control hypothalamic astrogliosis via apoA-I |
title_sort |
circulating hdl levels control hypothalamic astrogliosis via apoa-i |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2018-09-01 |
description |
Meta-inflammation of hypothalamic areas governing energy homeostasis has recently emerged as a process of potential pathophysiological relevance for the development of obesity and its metabolic sequelae. The current model suggests that diet-induced neuronal injury triggers microgliosis and astrocytosis, conditions which ultimately may induce functional impairment of hypothalamic circuits governing feeding behavior, systemic metabolism, and body weight. Epidemiological data indicate that low circulating HDL levels, besides conveying cardiovascular risk, also correlate strongly with obesity. We simulated that condition by using a genetic loss of function mouse model (apoA-I−/−) with markedly reduced HDL levels to investigate whether HDL may directly modulate hypothalamic inflammation. Astrogliosis was significantly enhanced in the hypothalami of apoA-I−/− compared with apoA-I+/+ mice and was associated with compromised mitochondrial function. apoA-I−/− mice exhibited key components of metabolic disease, like increased fat mass, fasting glucose levels, hepatic triglyceride content, and hepatic glucose output compared with apoA-I+/+ controls. Administration of reconstituted HDL (CSL-111) normalized hypothalamic inflammation and mitochondrial function markers in apoA-I−/− mice. Treatment of primary astrocytes with apoA-I resulted in enhanced mitochondrial activity, implying that circulating HDL levels are likely important for astrocyte function. HDL-based therapies may consequently avert reactive gliosis in hypothalamic astrocytes by improving mitochondrial bioenergetics and thereby offering potential treatment and prevention for obesity and metabolic disease. |
topic |
mitochondria inflammation high density lipoprotein apolipoprotein A-I metabolism dyslipidemia |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520335343 |
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