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

Daniel González-Hedström,María De La Fuente-Fernández,Antonio Tejera-Muñoz,Lucía Guerra-Menéndez,Sara Amor,Beatriz Martín-Carro,Ángel Luis García-Villalón,Miriam Granado,Riansares Arriazu

doi:10.3390/nu12020549

Abstract

Childhood obesity is associated with metabolic and cardiovascular comorbidities. The development of these alterations may have its origin in early life stages such as the lactation period through metabolic programming. Insulin resistance is a common complication in obese patients and may be responsible for the cardiovascular alterations associated with this condition. This study analyzed the development of cardiovascular insulin resistance in a rat model of childhood overweight induced by overfeeding during the lactation period. On birth day, litters were divided into twelve (L12) or three pups per mother (L3). Overfed rats showed a lower increase in myocardial contractility in response to insulin perfusion and a reduced insulin-induced vasodilation, suggesting a state of cardiovascular insulin resistance. Vascular insulin resistance was due to decreased activation of phosphoinositide 3-kinase (PI3K)/Akt pathway, whereas cardiac insulin resistance was associated with mitogen-activated protein kinase (MAPK) hyperactivity. Early overfeeding was also associated with a proinflammatory and pro-oxidant state; endothelial dysfunction; decreased release of nitrites and nitrates; and decreased gene expression of insulin receptor (IR), glucose transporter-4 (GLUT-4), and endothelial nitric oxide synthase (eNOS) in response to insulin. In conclusion, overweight induced by lactational overnutrition in rat pups is associated with cardiovascular insulin resistance that could be related to the cardiovascular alterations associated with this condition.

Highlights

Obesity is a main health concern worldwide due to its association with metabolic syndrome and cardiovascular diseases [1]
The aim of this work was to study if early overnutrition in rats results in a state of cardiovascular insulin resistance that may explain, at least in part, the cardiovascular alterations associated to this condition
In this study we show that early overnutrition in rats is associated with cardiovascular insulin resistance, both in the heart and in the aorta, and that this state may be responsible, at least in part, for the development of the cardiovascular alterations associated to this condition

Summary

Introduction

Obesity is a main health concern worldwide due to its association with metabolic syndrome and cardiovascular diseases [1]. In addition to metabolic disorders, obese children show cardiovascular alterations [5], such as arterial hypertension, whose incidence in obese children or adolescents is around 20%–25% [6]. Childhood obesity is correlated with left ventricular hypertrophy [7,8] and reduced systolic and diastolic function [9]. These cardiovascular alterations may be related, at least in part, with alterations in cardiovascular insulin sensitivity, as insulin exerts important effects on the cardiovascular system in physiological conditions [10]. It promotes vasodilation mainly through the release of nitric oxide [11], and in the heart it exerts a positive inotropic effect [12]

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