Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition

Experimental and clinical studies have demonstrated that early postnatal overnutrition represents a risk factor for later obesity and associated metabolic and cardiovascular disturbance. In the present study, we assessed the levels of glucose transporter 4 (GLUT-4), GLUT-1, insulin receptor (IR), IR...

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Bibliographic Details
Published in:	Journal of endocrinology Vol. 195; no. 3; pp. 485 - 494
Main Authors:	Rodrigues, Ananda L, De Souza, Érica P G, Da Silva, Simone V, Rodrigues, Dayane S B, Nascimento, Aline B, Barja-Fidalgo, Christina, De Freitas, Marta S
Format:	Journal Article
Language:	English
Published:	England BioScientifica 01-12-2007
Subjects:	Adipocytes - metabolism Adipose Tissue - pathology Aging - metabolism Animals Animals, Newborn Biological Transport - drug effects Body Weight Eating Epididymis - pathology Glucose - metabolism Glucose - pharmacokinetics Glucose Tolerance Test Glucose Transporter Type 4 - metabolism Hyperphagia - etiology Hyperphagia - pathology Insulin - metabolism Insulin - pharmacology Insulin Receptor Substrate Proteins Litter Size Male Overnutrition - complications Overnutrition - metabolism Overnutrition - pathology Phosphatidylinositol 3-Kinases - metabolism Phosphoproteins - metabolism Proto-Oncogene Proteins c-akt - metabolism Rats Rats, Wistar Regular papers Signal Transduction - physiology Weight Gain
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Summary:	Experimental and clinical studies have demonstrated that early postnatal overnutrition represents a risk factor for later obesity and associated metabolic and cardiovascular disturbance. In the present study, we assessed the levels of glucose transporter 4 (GLUT-4), GLUT-1, insulin receptor (IR), IR substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt expression, as well as insulin-stimulated glucose transport and Akt activity in adipocytes from adult rats previously raised in small litters (SL). The normal litter (NL) served as control group. We also investigated glycemia, insulinemia, plasma lipid levels, and glucose tolerance. Our data demonstrated that early postnatal overfeeding induced a persistent hyperphagia accompanied by a significant increase in body weight until 90 days of age. The SL group also presented a significant increase (∼42%) in epidydimal fat weight. Blood glucose, plasma insulin, and lipid levels were similar among the animals from the SL and NL groups. While insulin-stimulated glucose uptake was approximately twofold higher in adipocytes from the NL group, no stimulatory effect was observed in the SL group. The impaired insulin-stimulated glucose transport in adipose cells from the SL rats was associated with a significant decrease in GLUT-4, IRS-1 and PI3K expression, and Akt activity. In contrast, IR and Akt expression in adipocytes was not different between the SL and NL groups. Despite these alterations, our results showed no differences in glucose tolerance test in rats raised under different feeding conditions. Our findings reinforce a potent and long-term effect of neonatal overfeeding, which can program major changes in the metabolic regulatory mechanisms.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-0795 1479-6805
DOI:	10.1677/JOE-07-0046