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

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.

Supplementation with a Carob (Ceratonia siliqua L.) Fruit Extract Attenuates the Cardiometabolic Alterations Associated with Metabolic Syndrome in Mice

“…Thoracic segments were used for the vasodilation studies and abdominal segments for the vasoconstriction studies. The assembly of the segments was performed as previously described [39,40]. Changes in isometric force were recorded using a PowerLab data acquisition system (ADInstruments, Colorado Springs, CO, USA).…”

“…After euthanasia, hearts were immediately removed and mounted in the Langendorff perfusion system as previously described [40]. Briefly, after a 30 min equilibration period with constant flow perfusion, global ischemia was induced by stopping the flow perfusion for 30 min.…”

Programming of Cardiovascular Dysfunction by Postnatal Overfeeding in Rodents

“…Such an increase is believed to reflect insulin resistance [ 12 ], an hypothesis corroborated by a higher fasting glucose level in overfed animals [ 6 , 22 ] but also impaired glucose tolerance [ 7 , 9 , 22 , 26 , 54 ] and increased insulin secretion in response to glucose [ 7 , 39 ]. Plasma leptin levels were also shown to be higher in PNOF animals [ 7 , 21 , 22 , 37 , 46 , 55 ], an observation that could easily be explained by increased adiposity, since leptin production is released from adipocytes and the gene expression of leptin is increased in the white and brown adipose tissue of PNOF rats [ 56 ]. When adiposity is increased, circulating lipid levels are also disturbed in PNOF rodents.…”

“…When adiposity is increased, circulating lipid levels are also disturbed in PNOF rodents. Significant increases in free fatty acids, triglycerides and cholesterol content associated with decreased HDL-cholesterol levels were described in most studies [ 21 , 23 , 25 , 29 , 46 , 49 ], while some others did not detect any lipid level variations [ 6 ]. These discrepancies may be related to distinct strains, ages and pathophysiological conditions when lipid profiles were analysed.…”

“…Analyses of cardiovascular metabolism also demonstrated an alteration of insulin signalling in the myocardium of overfed rats [ 21 ] and mice, confirmed by decreased insulin receptor (IR)-β and IR substrate-1 (IRS) phosphorylation [ 36 ]. These impairments appear very early, since they are present at weaning in PNOF mice hearts with decreased expression of IRβ, pTyr-IRS1, phosphatidyl inositol-3 kinase (PI3K), type-4 glucose transporters (GLUT4) and pAkt/Akt, and increased expression of GLUT1 and pAMPKα/AMPKα content [ 38 ].…”