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Diabetes, Cardiovascular Risks, and Lipoproteins / Adipokines, Inflammation, and Metabolic Diseases · Journal article
Diabetes Obesity and Metabolism · August 9, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a preclinical protocol comparison study optimizing high-fat diet and streptozotocin-induced prediabetic mouse models by sex, designed to guide future metabolic research rather than test a therapeutic hypothesis. The work documents sex-dimorphic glucose metabolism (males dysregulate by week 12, females by week 16) and an unexpected STZ-induced reversal of lipid phenotype in females, but lacks human applicability and mechanistic insight needed to change practice.
Preclinical protocol comparison study, stratified by sex. Five-week-old C57BL/6J mice, stratified by sex.. Intervention: High-fat diet alone (12, 16, or 20 weeks) or HFD combined with streptozotocin (low or high cumulative dose).. Compared with: Multiple HFD-only and HFD-STZ protocols compared to characterize protocol differences; no untreated control described..
HFD induced obesity of equal magnitude in both sexes (non-significant Sex × Diet interactions for body weight and fat mass) In males, glucose and hepatic-lipid metabolism deteriorated by Week 12; females required 16 weeks to reach Pre-DM threshold at higher STZ dose HFD-STZ-L matched HFD-12w phenotype in both sexes within shorter cycle (overall success 73.3%)
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This study is intended for preclinical researchers designing metabolic disease models, not for clinical decision-making. The sex-stratified protocol recommendations may improve reproducibility and cost-efficiency of future animal studies but do not inform therapeutic efficacy or human disease management.
Protocol optimization study in animal models comparing five inbred mouse regimens; provides useful characterization for researchers but lacks clinical outcomes, human translation, or definitive evidence for therapeutic testing.
As stated by the source record.
Quoted from the source exactly as published.
This study is intended for preclinical researchers designing metabolic disease models, not for clinical decision-making. The sex-stratified protocol recommendations may improve reproducibility and cost-efficiency of future animal studies but do not inform therapeutic efficacy or human disease management.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
AIMS: Animal models of prediabetes (Pre-DM) are essential for studying metabolic disease and testing therapies, yet high-fat diet (HFD) and HFD-plus-streptozotocin (STZ) protocols vary in feeding duration, STZ dose, and diagnostic criteria and rarely account for sex. We compared five protocols in male and female C57BL/6J mice to find the best balance of duration, cost, and phenotypic stability and to characterize how HFD and HFD-STZ differ in their effects on glucose and lipid metabolism. MATERIALS AND METHODS: Five-week-old mice were stratified by sex and assigned to three HFD-only groups (HFD-12w, -16w, -20w) and two STZ groups of differing cumulative dose (HFD-STZ-L, -H). Body weight, food and energy intake, body fat percentage, fasting blood glucose (FBG), OGTT, ITT, fasting insulin, serum lipids, hepatic Oil Red O, histopathology, liver and kidney safety, and per-animal cost were assessed. RESULTS: HFD induced obesity of equal magnitude in both sexes (non-significant Sex × Diet interactions for body weight and fat mass). Glucose and hepatic-lipid metabolism showed clear sex dimorphism: in males these deteriorated by Week 12, whereas females required 16 weeks to reach the Pre-DM threshold, at a higher preset STZ dose. HFD-STZ-L matched HFD-12w in both sexes within a shorter cycle (overall success 73.3%). Notably, STZ reversed the HFD lipid phenotype, synchronously reducing body fat, serum lipids, and hepatic fat in females. CONCLUSIONS: HFD-STZ-L is preferred for glucose and β-cell studies in both sexes; HFD-12w preserves the intact female obesity phenotype; HFD-20w is preferred for MASLD studies. Biological sex must be incorporated into model design and phenotype interpretation.
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