Related Experiment Video
Updated: Jun 17, 2026
Development and Validation of a Methodology for Establishing Obese Rat Models with Typical Fatty Pancreas
Published on: November 11, 2025
Elevated insulin sensitivity in low-protein offspring rats is prevented by a high-fat diet and is associated with
Alison K Gosby1, Christopher A Maloney, Ian D Caterson
1Human Nutrition Unit, The University of Sydney, Sydney, New South Wales, Australia. alison.gosby@usyd.edu.au
Insights
Maternal low protein diet improves offspring insulin sensitivity. However, a high-fat postnatal diet reverses these benefits, increasing fat mass and preventing improved insulin sensitivity in offspring.
Area of Science:
- Metabolic Physiology
- Nutritional Science
- Endocrinology
Background:
- Maternal undernutrition during gestation and lactation can program offspring metabolism.
- Low-protein (LP) diets in dams are known to improve offspring insulin sensitivity (IS).
- The impact of postnatal high-fat diets on this programmed IS is not fully understood.
Purpose of the Study:
- To test if a high-fat postnatal diet negates the improved IS observed in offspring from mothers on a low-protein diet.
- To investigate the effects of a cafeteria diet on fat mass, energy balance, and hormonal profiles in offspring exposed to maternal low protein.
Main Methods:
- Wistar rat dams were fed either a control (20% protein) or low-protein (8% protein) diet during gestation and lactation.
- Offspring were weaned and fed either a control or cafeteria (high-fat) diet until 3 months of age.
- Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp; fat mass, energy intake/expenditure, and hormonal levels (leptin, adiponectin) were measured.
Main Results:
- Offspring from low-protein (LP) dams exhibited significantly increased insulin sensitivity compared to control (CON) offspring.
- Cafeteria feeding abolished the enhanced insulin sensitivity in LP offspring, bringing it to control levels.
- High-fat diet increased visceral fat mass and adiponectin levels in LP offspring, but prevented hyperinsulinemia and hyperleptinemia seen in CON offspring on the cafeteria diet.
Conclusions:
- Postnatal high-fat diet exposure prevents the beneficial effects of maternal low-protein diet on offspring insulin sensitivity.
- Increased visceral fat accumulation in LP offspring under high-fat conditions may contribute to the normalization of insulin sensitivity.
- Maternal nutrition and postnatal diet interact to influence offspring metabolic health, highlighting the importance of diet composition across developmental stages.
Abstract:
This study tests the hypothesis that a high-fat postnatal diet increases fat mass and reduces improved insulin sensitivity (IS) found in the low-protein model of maternal undernutrition. Offspring from Wistar dams fed either a 20% (control (CON)) or 8% (low protein (LP)) protein diet during gestation and lactation were randomly assigned to a control (con) or cafeteria (caf) diet at weaning (21 days) until 3 months of age at which point IS was measured (hyperinsulinemic-euglycemic clamp). Fat mass, growth, energy intake (EI) and expenditure (EE), fuel utilization, insulin secretion, and leptin and adiponectin levels were measured to identify a possible role in any changes in IS. IS was increased in LP-con in comparison to CON-con animals. Cafeteria feeding prevented this increase in LP animals but had no effect in CON animals (insulin-stimulated glucose infusion rates (GIRs; mg/min/kg); CON-con: 13.9 +/- 1.0, CON caf: 12.1 +/- 2.1, LP-con: 25.4 +/- 2.0, LP-caf: 13.7 +/- 3.7, P < 0.05). CON-caf animals had similar percent epididymal white adipose tissue (%EWAT; CON-con: 1.71 +/- 0.09 vs. CON-caf: 1.66 +/- 0.08) and adiponectin (microg/ml: CON-con: 4.61 +/- 0.34 vs. CON-caf: 3.67 +/- 0.18) except hyperinsulinemia and relative hyperleptinemia in comparison to CON-con. Differently, LP-caf animals had increased %EWAT (LP-con: 1.11 +/- 0.06 vs. LP-caf: 1.44 +/- 0.08, P < 0.05) and adiponectin (microg/ml: LP-con: 5.38 +/- 0.39 vs. LP-caf: 3.75 +/- 0.35, P < 0.05) but did not show cafeteria-induced hyperinsulinemia or relative hyperleptinemia. An increased propensity to store visceral fat in LP animals may prevent the elevated IS in LP offspring.
Related Concept Videos
01:24Type II Diabetes II: Pathophysiology
01:26Type II Diabetes I: Introduction