Key result
High-fat high-fructose diet plus STZ drives ~2.2-fold higher NT-proBNP and myocardial fibrosis in rats.
Why the study?
Establishing a reliable early-stage diabetic cardiomyopathy model is essential for mechanistic studies and therapeutic evaluation. This study aimed to characterize an early-stage diabetic cardiomyopathy model in male Sprague–Dawley rats using a High-Fat High-Fructose diet combined with low-dose Streptozotocin.
Does a 12-week high-fat high-fructose diet combined with low-dose streptozotocin (25 mg/kg or 40 mg/kg) induce early-stage diabetic cardiomyopathy with myocardial remodeling and elevated NT-proBNP in male Sprague-Dawley rats?
Does a 12-week high-fat high-fructose diet combined with low-dose streptozotocin (25 mg/kg or 40 mg/kg) induce early-stage diabetic cardiomyopathy with myocardial remodeling and elevated NT-proBNP in male Sprague-Dawley rats?
A 12-week high-fat high-fructose diet followed by low-dose streptozotocin (25 or 40 mg/kg) in rats successfully models subclinical, early-stage diabetic cardiomyopathy characterized by elevated NT-proBNP and histological myocardial fibrosis prior to overt echocardiographic dysfunction.
Establishes a rat model of early diabetic cardiomyopathy with preserved EF; leaves open translation to human disease.
Background: Diabetic Cardiomyopathy (DCM) is defined as structural and functional abnormalities of the myocardium occurring in individuals with Diabetes Mellitus (DM) in the absence of other conventional cardiovascular risk factors. Establishing a reliable early-stage DCM model is essential for mechanistic studies and therapeutic evaluation. This study aimed to characterize an early-stage DCM model in male Sprague–Dawley rats using a High-Fat High-Fructose (HFHF) diet combined with low-dose Streptozotocin (STZ). Methods: Twelve male Sprague–Dawley rats (7–8 weeks, 200–250 g) were randomly assigned to three groups (n=4/group): control, HFHF + STZ 25 mg/kg, and HFHF + STZ 40 mg/kg. Rats received an HFHF diet for 12 weeks, followed by intraperitoneal STZ induction. Fasting blood glucose, lipid profile, cardiac echocardiography, serum N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP), and myocardial histopathology were assessed. Data were analyzed using ANOVA or Kruskal–Wallis as appropriate. Results: Both STZ doses induced persistent hyperglycemia without significant body-weight changes, consistent with a DCM metabolic phenotype. NT-proBNP levels were significantly elevated in both STZ groups compared with controls (p<0.05), indicating early myocardial stress despite preserved systolic and diastolic function on echocardiography. Histopathological evaluation showed increased inflammatory cell infiltration and progressive fibrosis in the HFHF+STZ groups, with a graded pattern across STZ doses. Conclusions: The combination of an HFHF diet and low-dose STZ reproduced an early-stage DCM model characterized by persistent hyperglycemia, elevated NT-proBNP, and early myocardial remodeling while cardiac function remains preserved. This model reflects early DCM and is suitable for mechanistic studies and for testing therapies aimed at preventing progression to advanced myocardial dysfunction.
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Atmojo et al. (2026) studied Early-Stage Diabetic Cardiomyopathy (Preclinical Rat Model) (n=12). High-Fat High-Fructose (HFHF) diet combined with low-dose Streptozotocin (STZ) vs. Standard chow without STZ induction was evaluated on Serum N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP) levels (pg/mL) at week 15 (p=0.001). High-fat high-fructose diet plus low-dose STZ significantly elevated NT-proBNP (1121.7 and 1367.6 vs 624.3 pg/mL, p=0.001) and myocardial fibrosis in rats despite preserved ejection fraction.
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