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

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 (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.

High fat diet induces alterations to intraepithelial lymphocyte and cytokine mRNA in the small intestine of C57BL/6 mice

“…42 Similarly, West et al did not nd any difference on glucose blood levels in several mice strains feed with HFD. 43 Discordance on these results could be due to different fatty acid prole on diet formulation, 42,44,45 time of feeding mice, 46,47 and mouse strain used. 43,48 Thus, the effect of HFD induced obesity on iIELs was associated rstly with HFD induced obesity and not by other biochemical changes such as high levels of glucose (linked to type 2 diabetes mellitus) or cholesterol (linked to cardiovascular disease).…”