The diet-induced obese mouse

A standard mouse model of diet-induced obesity for drug efficacy testing.

Standard model for profiling drug

therapeutic effects in obesity Key model traits

• Obesity and adiposity.

High-fat diet-induced obese (DIO) mouse is the most common
• Prediabetes characterized by insulin resistance and impaired
mouse model employed in preclinical obesity drug development.
glucose tolerance.
• Similar dysmetabolic phenotype in mice and rats.
• Treatment efficacy across a wide range of anti-obesity and
anti-diabetic drug classes.

HFD 60% fat (Ssniff #D12492) Diet-induced obesity mice are enrolled into studies after ≥18 weeks of high-fat diet
Diet
Chow (Altromin 1324) induction. Age-matched chow-fed animals serve as lean controls.

Strain C57BL/6JRj

Study outline

Chronic repeated dosing (SC/PO, QD/BID)

BW (QD)
FI (QD)
Randomization
+ Baseline
(HFD-maintenance) In vivo study period
HFD-induction Histology/Assay
(HFD-maintenance)

✚ FI
✚ BW
Week -16 (+) Week -1 Day 1 Week 3 Week 4
Randomization First Dose
✚ EchoMRI ✚ OGTT/IPGTT ✚ EchoMRI Terminal Biochemistry:
✚ Fasting BG
✚ BW ✚ Termination ✚ Fasting PI
✚ Fat tissue mass - Tissue weight ✚ Fasting P-TG/P-TC
✚ Liver TG/TC

Tissue/Blood samples:
✚ Terminal plasma for
sponsor
Frequency Measurements ✚ Terminal tissue (frozen)
QD: Once a day BW: Body weight for sponsor
BID: Twice daily FI: Food intake
BG: Blood glucose
Route PI: Plasma insulin
SC: Subcutaneous P-TG: Plasma triglycerides
PO: Oral gavage P-TC: Plasma total cholesterol

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Body weight,
food intake
and glucose
tolerance
4 weeks of liraglutide
(GLP-1 agonist)
treatment promotes
robust weight loss,
appetite suppression
and improves glucose
tolerance in DIO mice.

10
1000
Fasted blood glucose (mM)

8 ***
Plasma insulin (pg/ml)

800
***
6
600

4 ** **
400

2
200

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hyperinsulinemia and
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elevated plasma levels of

cholesterol and reduced
levels of triglycerides.
Liraglutide treatment for
1.0
8 4 weeks improves blood
Plasma triglycerides (mM)

Plasma total cholesterol (mM)

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