Does rosiglitazone affect adiposity and cardiac function in genetic diabetic mice?

Area of Science:

• Pharmacology
• Cardiology
• Diabetology

Background:

• Preclinical rodent models inadequately predict rosiglitazone (RGZ)-induced adverse drug effects in diabetic patients.
• The Akita mouse, with a genetic predisposition to diabetes, offers a potential model for studying these mechanisms.

Purpose of the Study:

• To evaluate the effects of RGZ on adipose tissue and cardiac function in diabetic Akita mice.
• To assess the utility of the Akita mouse model for anti-diabetic drug safety testing.

Main Methods:

• Diabetic Akita mice and wild-type (WT) littermates were fed a high-fat, high-cholesterol diet (HF-HCD) for 4 months.
• Mice were treated with RGZ (10mg/kg/day or 30mg/kg/day) and assessed for weight, fat volume, adipocyte size, and cardiac function (intraventricular septum thickness, cardiac output, fractional shortening, ejection fraction).

Main Results:

• Untreated Akita mice exhibited less weight gain and reduced fat volume compared to WT mice, with smaller adipocytes.
• RGZ treatment (10mg/kg/day) increased weight gain and fat volume in Akita mice, without altering adipocyte size or macrophage infiltration.
• RGZ treatment (30mg/kg/day) in Akita mice led to increased intraventricular septum thickness and cardiac output, but did not affect fractional shortening or ejection fraction.

Conclusions:

• Rosiglitazone promotes adiposity and early signs of hypertrophic cardiomyopathy in the diabetic Akita mouse model.
• The genetically modified Akita mouse is a suitable model for evaluating the safety of anti-diabetic drugs.