MaRGA Meeting, 2004: Abstracts

3: Nutrition

The Marmoset as a Model of Diet Induced Obesity

Mark Paulik¹, Diane Ignar¹, Mary Lancaster¹, Tula Miliken¹, Wesley Young¹, Christy Britt¹, Lisa Clifton¹, Rick Bertram², Carmen McLamb² and Tom Tlusty²

Affiliation: ¹Metabolic Diseases and Virology Center of Excellence in Drug Discovery; and ²Laboratory Animal Science, Glaxo Smith Kline, Research Triangle Park, NC

Obesity has become a major public health concern in the United States. A predictive preclinical model of diet-induce obesity (DIO) could accelerate the development of pharmaceuticals to treat this rising epidemic. A non-human primate could provide such a predictive model. Thus, the common marmoset (Callithrix jacchus) was evaluated for its propensity to becoming obese when challenged with high fat diets. Marmosets were placed on either a standard diet (Mazuri 5MI5) (SD), or a SD supplemented with 12% or 24% lard. The marmosets fed the 12% lard diet (HF) for 8 weeks gained the most weight when compared with the 24% lard or the SD groups. Marmosets placed on the HF diet for 3 months had a 27% increase in body weight, a 51% increase in fat mass, and a 25% increase in lean mass. In addition, the marmosets on the HF diet had significant increases in total serum cholesterol, LDL-cholesterol, triglycerides, Hb lAc, glucose, insulin and creatine kinase when compared to marmosets on SD. To determine how marmosets would respond to pharmaceutical intervention, male marmosets were dosed with a CB-1 antagonist (15 and 45 mg/kg) or with Sibutramine (5 and 15 mg/kg) for four weeks. Compared to vehicle treated animals, the Sibutramine groups lost 2.3% and 7.9% weight, respectively. Whereas, the CB-1 antagonist treated marmosets lost 9.5% and 17.4% of their starting weights, respectively. Furthermore, CB-1 antagonist (45 mg/kg) treated marmosets demonstrated significant lowering of serum triglycerides vs. vehicle control animals. After initial evaluation, the common marmoset shows promise as a DIO model.