Overfeeding During Lactation in Rats is Associated with Cardiovascular Insulin Resistance in the Short-Term

Area of Science:

• Metabolic and cardiovascular research
• Developmental programming
• Pediatric obesity

Background:

• Childhood obesity is linked to metabolic and cardiovascular issues.
• Metabolic programming during early life stages, like lactation, may cause these alterations.
• Insulin resistance is a common complication in obese individuals, potentially causing cardiovascular changes.

Purpose of the Study:

• To investigate cardiovascular insulin resistance in a rat model of childhood overweight.
• To analyze the effects of overfeeding during lactation on cardiovascular function and insulin signaling pathways.

Main Methods:

• Lactational overfeeding induced overweight in rat pups (L12 vs. L3 litters).
• Assessed myocardial contractility and insulin-induced vasodilation.
• Analyzed phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways.
• Evaluated inflammatory markers, oxidative stress, endothelial function, and gene expression (IR, GLUT-4, eNOS).

Main Results:

• Overfed rats exhibited reduced myocardial contractility and vasodilation in response to insulin.
• Vascular insulin resistance was linked to decreased PI3K/Akt pathway activation.
• Cardiac insulin resistance correlated with MAPK hyperactivity.
• Early overnutrition led to a proinflammatory, pro-oxidant state, endothelial dysfunction, and altered gene expression of IR, GLUT-4, and eNOS.

Conclusions:

• Lactational overnutrition in rats induces cardiovascular insulin resistance.
• This condition is associated with impaired insulin signaling, endothelial dysfunction, and inflammation.
• Early-life overfeeding may contribute to cardiovascular alterations seen in childhood obesity.