Model Organisms in Drug Discovery

these proteins may be targets for novel obesity therapies. In addition, DEXA
was used to show that the small-molecule insulin mimetic cpd2 blocks the
accumulation of body fat in mice fed a high fat diet, an observation that was
confirmed by direct analysis of fat pad weights (Air et al., 2002). A DEXA
instrument (Lunar Piximus) is used to record bone mineral density, bone
mineral content, percent body fat and total tissue mass (Nagy and Clair, 2000;
Punyanitya et al., 2000). Although primarily aimed at metabolic and
osteoporotic conditions, DEXA is a sensitive measure of all-round wellbeing
and often contributes to diagnosis in other therapeutic areas.
Level 2 obesity tests
In Level 2, obesity targets are analyzed to determine whether they regulate
metabolism, feeding, appetite or food absorption. Level 2 obesity tests include:
. Metabolic cages to measure food intake, water intake and fat malabsorption
. Mini-Mitter telemetry for physical activity, core body temperature,
drinking frequency and feeding frequency and duration
. Oxymax measurement of metabolic rate and physical activity
. Home cage diet studies, including high-fat-diet challenge, food intake
measurement and pair-feeding studies
. Fat mass by DEXA or nuclear magnetic resonance (Bruker Minispec)
. Body composition analysis (analysis of carcass fat mass by Sohxlet; fat pad
and organ weights)
. Crosses to ob/ob mice
. Pharmacological challenge with leptin, melanocortin II and neuropeptide
Y
. Blood pressure
Level 1 osteoporosis tests
Bone microcomputed tomography
HIGH-THROUGHPUT BIOLOGY 261
Osteoporosis is characterized by a decreased bone mineral density due to a
deficiency in bone production or increased bone absorption resulting in brittle
bones. Specialized microcomputed tomography (micro-CT) machines have