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Differential lipid ...
Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice
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- Prieur, Xavier (författare)
- Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Institut du Thorax, Institut National de la Santé et de la Recherche Médicale U915, Nantes, France
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- Mok, Crystal Y. L. (författare)
- Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
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- Velagapudi, Vidya R (författare)
- Technical Research Centre of Finland (VTT), Espoo, Finland
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- Núñez, Vanessa (författare)
- Department of Regenerative Cardiology, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
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- Fuentes, Lucía (författare)
- Department of Regenerative Cardiology, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
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- Montaner, David (författare)
- Department of Bioinformatics and Genomics, Functional Genomics Node (INB) at CIPF, Centro de Investigación Príncipe Felipe (CIFP), Valencia, Spain
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- Ishikawa, Ko (författare)
- Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
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- Camacho, Alberto (författare)
- Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
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- Barbarroja, Nuria (författare)
- Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
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- O'Rahilly, Stephen (författare)
- Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
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- Sethi, Jaswinder K (författare)
- Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
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- Dopazo, Joaquin (författare)
- Department of Regenerative Cardiology, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
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- Oresic, Matej, 1967- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Technical Research Centre of Finland (VTT), Espoo, Finland
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- Ricote, Mercedes (författare)
- Department of Regenerative Cardiology, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
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- Vidal-Puig, Antonio (författare)
- Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
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(creator_code:org_t)
- 2011-02-21
- 2011
- Engelska.
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 60:3, s. 797-809
- Relaterad länk:
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https://doi.org/10.2...
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http://diabetes.diab...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- OBJECTIVE: Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the current study we investigated the concept of lipid-induced toxicity as the pathogenic link that could explain the trigger of this response.RESEARCH DESIGN AND METHODS: We addressed this question using isolated ATMs and adipocytes from genetic and diet-induced murine models of obesity. Through transcriptomic and lipidomic analysis, we created a model integrating transcript and lipid species networks simultaneously occurring in adipocytes and ATMs and their reversibility by thiazolidinedione treatment.RESULTS: We show that polarization of ATMs is associated with lipid accumulation and the consequent formation of foam cell-like cells in adipose tissue. Our study reveals that early stages of adipose tissue expansion are characterized by M2-polarized ATMs and that progressive lipid accumulation within ATMs heralds the M1 polarization, a macrophage phenotype associated with severe obesity and insulin resistance. Furthermore, rosiglitazone treatment, which promotes redistribution of lipids toward adipocytes and extends the M2 ATM polarization state, prevents the lipid alterations associated with M1 ATM polarization.CONCLUSIONS: Our data indicate that the M1 ATM polarization in obesity might be a macrophage-specific manifestation of a more general lipotoxic pathogenic mechanism. This indicates that strategies to optimize fat deposition and repartitioning toward adipocytes might improve insulin sensitivity by preventing ATM lipotoxicity and M1 polarization.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Diabetes
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Prieur, Xavier
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Mok, Crystal Y. ...
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Velagapudi, Vidy ...
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Núñez, Vanessa
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Fuentes, Lucía
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Montaner, David
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Ishikawa, Ko
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Camacho, Alberto
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Barbarroja, Nuri ...
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O'Rahilly, Steph ...
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Sethi, Jaswinder ...
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Dopazo, Joaquin
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Oresic, Matej, 1 ...
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Ricote, Mercedes
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Vidal-Puig, Anto ...
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- MEDICIN OCH HÄLSOVETENSKAP
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- Artiklar i publikationen
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Diabetes
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Örebro universitet