Hamsters fed a highly palatable fat- and
sugar-rich diet (HPFS) for 12 weeks showed significant
body weight gain, body fat accumulation and
impaired glucose tolerance.
Cholesterol supplementation to the diet evoked additional
hypercholesterolemia. Chronic treatment with the
GLP-1 analogue,
liraglutide (0.2 mg/kg, SC, BID, 27 days), normalized
body weight and
glucose tolerance, and lowered blood
lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4) inhibitor,
linagliptin (3.0 mg/kg, PO, QD) also improved
glucose tolerance. Treatment with
peptide YY3-36 (PYY3-36, 1.0 mg/kg/day) or
neuromedin U (NMU, 1.5 mg/kg/day), continuously infused via a subcutaneous osmotic minipump for 14 days, reduced
body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with
liraglutide and PYY3-36 evoked a pronounced synergistic decrease in
body weight and food intake with no lower plateau established. Treatment with the
cholesterol uptake inhibitor
ezetimibe (10 mg/kg, PO, QD) for 14 days lowered plasma total
cholesterol with a more marked reduction of
LDL levels, as compared to HDL, indicating additional sensitivity to
cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined
obesity,
impaired glucose tolerance and
hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-
obesity, anti-diabetic and
lipid modulating agents.