Early overnutrition impairs insulin signaling in the heart of adult Swiss mice

Abstract

Human overnutrition has caused a rise in the prevalence of obesity in recent years. In addition to the deleterious effects of obesity during childhood, long-term effects in adulthood have been described as well. For instance, cardiovascular diseases and type 2 diabetes are among the diseases associated with a history of obesity. Altered insulin secretion and action have been described as important links between these diseases and obesity. Insulin acts as a unique anabolic hormone providing regulation of wholebody glucose homeostasis and peripheral tissue glucose uptake in tissues such as the heart. In this study, we examined insulin signaling in the heart of obese animals using an experimental model of inducing overweight adult animals by overnutrition in early life. In these animals, overfeeding during lactation was able to induce a significant increase in body weight starting at the 10th day of life, and this increased weight persisted until adulthood. Impairment in glucose tolerance, hyperinsulinemia, and an increased insulin/glucose ratio were also observed in these animals. Moreover, an increased heart weight/tibia length ratio was also observed, indicating an enlarged heart size. The overfed animals also had decreased insulin sensitivity in the heart, as confirmed by decreased insulin receptor (IR)-b and IR substrate-1 (Irs1) phosphorylation, increased phosphatase, non-receptor type 1 (Ptpn1)-IR-b association, decreased -Irs1-associated activity, and reduction in anti-phospho Akt1 phosphorylation. In conclusion, our findings showed that overnutrition during early life induced obesity and insulin resistance in the adult offspring, and further increased heart size and impaired cardiac insulin signaling, putatively due to an increase in Ptpn1 activity.

Oxidative stress programming in a rat model of postnatal early overnutrition — role of insulin resistance

“…Previously, Rodrigues et al [14] have demonstrated, in the 90-day-old SL rats, lower IRS1, PI-3K and GLUT-4 expressions and lower Akt activity in adipocytes. Also, Martins et al [37] have found that 150 days-old SL Swiss mice had decreased insulin sensitivity in the heart. However, in 1-year-old SL rats, no changes in liver and heart insulin pathway signaling were observed [38].…”

Early Postnatal Nutrition Determines Adult Physical Activity and Energy Expenditure in Female Mice

“…The early postnatal exposure induces elevated body weight and adiposity that persists to adulthood (10–12), with concomitant increases in plasma insulin (11,13) and leptin concentrations (13) and impaired glucose tolerance (11,13,14). It remains unresolved, however, whether the sustained increase in adiposity of adult SL rodents results from increased energy intake or decreased energy expenditure (13,15). Moreover, the fundamental mechanisms by which the metabolic effects of SL exposure persist to adulthood are unknown.…”

At the heart of programming: the role of micro-RNAs

“…These exposures change the programming of cardiac metabolism, inducing excessive lipid accumulation in myocardial cells 54,34 and defects in cardiac insulin signaling. 53 In the early origin of cardiac dysfunctions, the existence of sensitive developmental windows of exposure had been only addressed in a few studies which highlighted the impact levels according to the time of exposure. In the case of high-fat diet, adult cardiac alterations including increased heart rate were described when the exposure occurred after weaning.…”