Obesity, Diabetes and Metabolic Syndrome

Obesity is a condition that poses significant health risks and complications. Several complications of obesity include: diabetes (type 2), heart and vascular diseases, and hypertension known collectively as the Metabolic syndrome. In a manner similar to humans, rats and mice fed highly caloric or other diets may become obese, diabetic and/or develop the Metabolic syndrome. These conditions can be triggered or exacerbated in genetically prone strains. Both the response to disease induction and to drug treatment can be compared in outbred, inbred and genetically modified strains differing in susceptibility to obesity and diabetes.

Category(s)

Preclinical Drug Efficacy Studies

Species

Murine (Mice and Rats) – Various strains are available and may include those with a genetic propensity to develop obesity, diabetes (type 2) and/or the Metabolic syndrome. Below is a list of strains commonly employed in studies:

  • Mice C57BL/6J or 6N, ob/ob, db/db
  • Rats Sprague-Dawley, Zucker fatty diabetic rat (ZDF), Zucker fatty rat

Basic Methodology

After an initial acclimation period, mice or rats are individually housed and placed on either a maintenance diet or a diet containing a nutritional formulation modified to induce or exacerbate obesity, type 2 diabetes or other metabolic-related condition. Animals may be maintained on these diets for up to 3-months. Animals are weighed weekly, blood is collected, and GTT and/or insulin suppression tests may be conducted at time points specified by the experimental protocol. The administration of therapeutic compounds is performed according to the schedule set-forth in the study protocol.

Measurements

Clinical observations, body weight, glucose tolerance testing (GTT) and insulin suppression testing, serum lipid panels and other blood chemistries, organ and adipose depot morphology and histopathology, cytokine/endocrine profiling using ELISA and Luminex multiplex assays

Reference Substance(s):

Rosiglitazone, Metaformin

Literature References:

Reifsnyder PC and Leiter EH. (2002) Deconstructing and Reconstructing Obesity-Induced Diabetes (Diabesity) in Mice. Diabetes; 51: 825-832.

Srinivasan K and Ramarao P. (2007) Animal models in type 2 diabetes research: An overview. Indian Journal of Medical Research; 125: 451-472.