Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet
The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO) model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma a...
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2010-01-01
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doaj-cae9bc5d7d7f4e2ba1dbbdd988dcff992020-11-24T22:07:17ZengHindawi LimitedPPAR Research1687-47571687-47652010-01-01201010.1155/2010/970164970164Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol DietLaura W. Engstrom0Loretta Bober1Shu-Cheng Chen2Jay S. Fine3Ying Li4Michaela C. Stanton5David Kinsley6Long Cui7James V. Jackson8Alberto Rojas-Triana9Daniel Lundell10Maureen Laverty11Eric L. Gustafson12Chung-Her Jenh13Timothy J. Kowalski14Denise J. Manfra15Department of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Cardiovascular and Metabolic Disease, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of In vivo and Translational Biology, Hoffman-LaRoche, Nutley, NJ 070110, USADepartment of Respiratory, Inflammation, and Autoimmunity, MedImmune, Gaithersburg, MD 20878, USADepartment of Cardiovascular and Metabolic Disease, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Cardiovascular and Metabolic Disease, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Cardiovascular and Metabolic Disease, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADiscovery Technologies Department, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADiscovery Technologies Department, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Cardiovascular and Metabolic Disease, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Cardiovascular and Metabolic Disease, Schering-Plough Research Institute, Kenilworth, NJ 07033, USADepartment of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, USAThe kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO) model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/0.12% cholesterol (HF/CH) or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM). Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF), stromal vascular fraction (SVF), and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg) for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6.http://dx.doi.org/10.1155/2010/970164 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laura W. Engstrom Loretta Bober Shu-Cheng Chen Jay S. Fine Ying Li Michaela C. Stanton David Kinsley Long Cui James V. Jackson Alberto Rojas-Triana Daniel Lundell Maureen Laverty Eric L. Gustafson Chung-Her Jenh Timothy J. Kowalski Denise J. Manfra |
spellingShingle |
Laura W. Engstrom Loretta Bober Shu-Cheng Chen Jay S. Fine Ying Li Michaela C. Stanton David Kinsley Long Cui James V. Jackson Alberto Rojas-Triana Daniel Lundell Maureen Laverty Eric L. Gustafson Chung-Her Jenh Timothy J. Kowalski Denise J. Manfra Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet PPAR Research |
author_facet |
Laura W. Engstrom Loretta Bober Shu-Cheng Chen Jay S. Fine Ying Li Michaela C. Stanton David Kinsley Long Cui James V. Jackson Alberto Rojas-Triana Daniel Lundell Maureen Laverty Eric L. Gustafson Chung-Her Jenh Timothy J. Kowalski Denise J. Manfra |
author_sort |
Laura W. Engstrom |
title |
Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet |
title_short |
Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet |
title_full |
Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet |
title_fullStr |
Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet |
title_full_unstemmed |
Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet |
title_sort |
kinetic assessment and therapeutic modulation of metabolic and inflammatory profiles in mice on a high-fat and cholesterol diet |
publisher |
Hindawi Limited |
series |
PPAR Research |
issn |
1687-4757 1687-4765 |
publishDate |
2010-01-01 |
description |
The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO) model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/0.12% cholesterol (HF/CH) or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM). Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF), stromal vascular fraction (SVF), and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg) for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6. |
url |
http://dx.doi.org/10.1155/2010/970164 |
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