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 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 ( approximately 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.
Rodrigues
Ananda L
AL
Department of Pharmacology, Institute of Biology, State University of Rio de Janeiro, Av. 28 de setembro 87 fds, Vila Isabel, Rio de Janeiro 20551-030, RJ, Brazil.
De Souza
Erica P G
EP
Da Silva
Simone V
SV
Rodrigues
Dayane S B
DS
Nascimento
Aline B
AB
Barja-Fidalgo
Christina
C
De Freitas
Marta S
MS
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000473:pathology; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight; D004435:Eating; D004822:Epididymis / Q000473:pathology; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006963:Hyperphagia / Q000209:etiology / Q000473:pathology; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D008098:Litter Size; D008297:Male; D044343:Overnutrition / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D015430:Weight Gain
D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; C495694:Slc2a4 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose