title: 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.
authors.affiliation: Department of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: Laura W
authors.initials: LW
authors.lastname: Engstrom
authors.forename: Loretta
authors.initials: L
authors.lastname: Bober
authors.forename: Shu-Cheng
authors.initials: SC
authors.lastname: Chen
authors.forename: Jay S
authors.initials: JS
authors.lastname: Fine
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Michaela C
authors.initials: MC
authors.lastname: Stanton
authors.forename: David
authors.initials: D
authors.lastname: Kinsley
authors.forename: Long
authors.initials: L
authors.lastname: Cui
authors.forename: James V
authors.initials: JV
authors.lastname: Jackson
authors.forename: Alberto
authors.initials: A
authors.lastname: Rojas-Triana
authors.forename: Daniel
authors.initials: D
authors.lastname: Lundell
authors.forename: Maureen
authors.initials: M
authors.lastname: Laverty
authors.forename: Eric L
authors.initials: EL
authors.lastname: Gustafson
authors.forename: Chung-Her
authors.initials: CH
authors.lastname: Jenh
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kowalski
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Manfra
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