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

Engstrom, L.W., Bober, L., Chen, S., Fine, J.S., Ying, L., Stanton, M.C., Kinsley, D., Cui, L., Jackson, J.V., Rojas-Triana, A., Lundell, D., Laverty, M., Gustafson, E.L., Jenh, C., Kowalski, T.J., Manfra, D.J.
Journal   PPAR Research.
Species  
Analytes Measured   Adiponectin , GM-CSF , IL-10 , IL-12 p70 , IL-6 , Insulin , Leptin , Resistin
Matrix Tested   Serum, epididymal fat tissue lysates
Year   2010
Volume   2010
Page Numbers  
Application   Metabolic
Abstract
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 (5mg/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.

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