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Development and Validation of a Methodology for Establishing Obese Rat Models with Typical Fatty Pancreas
Published on: November 11, 2025
Developmental changes in gut microbiota and enzyme activity predict obesity risk in rats arising from reduced nests
Z Šefčíková1, D Bujňáková, Ľ Raček
1Institute of Animal Physiology, Slovak Academy of Sciences, Košice, Slovak Republic.
Insights
Early overnutrition in rat pups programs increased fat deposition and altered gut microbiota, even after normalizing nutrition post-weaning. This early nutritional imprint significantly impacts long-term obesity development.
Area of Science:
- Developmental biology
- Nutritional science
- Microbiology
Background:
- Early life nutrition significantly influences long-term health outcomes.
- The gut microbiota plays a crucial role in host metabolism and development.
- Understanding early nutritional programming is key to preventing obesity.
Purpose of the Study:
- To investigate the impact of preweaning overnutrition on the developing intestinal microbiota and alkaline phosphatase (AP) activity.
- To determine if early nutritional programming influences growth and obesity parameters in Sprague-Dawley rats.
- To assess the persistence of these effects under normalized postweaning nutrition.
Main Methods:
- Male Sprague-Dawley rats were assigned to small litters (SL, 4 pups) or normal litters (NL, 10 pups) to manipulate preweaning nutrition.
- Jejunal and colonic Lactobacillus/Enterococcus (LAB) and Bacteroides/Prevotella (BAC) were quantified using Fluorescence In Situ Hybridization (FISH).
- Jejunal alkaline phosphatase (AP) activity was measured histochemically; growth and adiposity were assessed at 15, 20, and 40 days.
Main Results:
- SL pups exhibited higher body weight and adiposity compared to NL pups at 15 and 20 days.
- Preweaning overnutrition led to significantly higher jejunal and colonic LAB and lower BAC in SL pups.
- SL pups showed higher jejunal AP activity, and these differences persisted to day 40 despite normalized postweaning nutrition.
Conclusions:
- Early life overnutrition establishes a lasting imprint on intestinal microbiota composition and alkaline phosphatase activity.
- The observed changes in gut parameters during suckling persist postweaning and contribute to enhanced fat deposition.
- Early nutritional interventions are critical for preventing obesity, highlighting the gut's role in nutritional programming.
Abstract:
The aim of the study was to assess the impact of preweaning overnutrition upon the ontogeny of intestinal microbiota, alkaline phosphatase activity (AP) and parameters of growth and obesity in male Sprague-Dawley rats. We tested whether intestinal characteristics acquired in suckling pups could programme the development of enhanced fat deposition during normalized nutrition beyond weaning. Postnatal nutrition was manipulated by adjusting the number of pups in the nest to 4 (small litters--SL) and 10 (normal litters--NL). In the postweaning period both groups were fed with a standard diet. The jejunal and colonic Lactobacillus/Enterococcus (LAB) and the Bacteroides/Prevotella (BAC) were determined using the FISH technique, and the jejunal AP activity was assayed histochemically. At 15 and 20 days of age the SL pups became heavier, displayed increased adiposity accompanied by significantly higher LAB and lower numbers of BAC and with higher AP activity in comparison with rats nursed in NL nests. These differences persisted to day 40 and withdrawal of the previous causal dietary influence did not prevent the post-weaning fat accretion. These results reveal the significance of early nutritional imprint upon the gut microbial/functional development and allow better understanding of their involvement in the control of obesity.
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