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PPAR Research
Volume 2010 (2010), Article ID 970164, 13 pages
Research Article

Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet

1Department of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA
2Department of Cardiovascular and Metabolic Disease, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA
3Department of In vivo and Translational Biology, Hoffman-LaRoche, Nutley, NJ 070110, USA
4Department of Respiratory, Inflammation, and Autoimmunity, MedImmune, Gaithersburg, MD 20878, USA
5Discovery Technologies Department, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA

Received 19 August 2009; Revised 20 November 2009; Accepted 9 February 2010

Academic Editor: Joshua K. Ko

Copyright © 2010 Laura W. Engstrom et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.