Chronic Obesity Models

Both the Zucker fa/fa rat and Diet induced obesity models provide a means to study effect of an NCE on multiple endpoints important for determining its potential as an anti-obesity therapy. A brief overview of endpoints that Transpharmation can measure and how these compare between the two models is presented below.

Endpoint	Zucker model	DIO model
Body mass	~50% > vs. lean controls	~30% > vs. controls
Body composition (QMR)	Fat mass ~35% vs. ~7% lean controls Lean mass ~56% vs. 80% lean controls	Fat mass ~20% vs. ~10% controls Lean mass ~59% vs. 75% controls
Food and water intake	Food and water intake elevated vs. lean controls.	Food and water intake actuall reduced vs. lean controls (based on high fat diet).
Lipid profile	TG's + Cholesterol elevated vs. lean controls	TG's + Cholesterol modestly elevated vs. lean controls
Blood insulin levels	Severe hyperinsulinaemia	Hyperinsulinaemia
Blood glucose levels	Hyperglycemia	Normal blood glucose levels
Glucose tolerance test	Elevated blood [glucose] following load - 2x AUC vs. lean controls.	Elevated blood [glucose] following load - 1.5x AUC vs. controls.
Behavioural profile	Hypoactive, allodynia to a tactile stimulus vs. lean conrols	Hypoactive vs. controls.