Maternal protein restriction during early lactation induces GLUT4 translocation and mTOR/Akt activation in adipocytes of adult rats.
Epidemiological and experimental studies have demonstrated that early postnatal nutrition has been associated with long-term effects on glucose homeostasis in adulthood. Recently, our group demonstrated that undernutrition during early lactation affects the expression and activation of key proteins of the insulin signaling cascade in rat skeletal muscle during postnatal development. To elucidate the molecular mechanisms by which undernutrition during early life leads to changes in insulin sensitivity in peripheral tissues, we investigated the insulin signaling in adipose tissue. Adipocytes were isolated from epididymal fat pads of adult male rats that were the offspring of dams fed either a normal or a protein-free diet during the first 10 days of lactation. The cells were incubated with 100 nM insulin before the assays for immunoblotting analysis, 2-deoxyglucose uptake, immunocytochemistry for GLUT4, and/or actin filaments. Following insulin stimulation, adipocytes isolated from undernourished rats presented reduced tyrosine phosphorylation of IR and IRS-1 and increased basal phosphorylation of IRS-2, Akt, and mTOR compared with controls. Basal glucose uptake was increased in adipocytes from the undernourished group, and the treatment with LY294002 induced only a partial inhibition both in basal and in insulin-stimulated glucose uptake, suggesting an involvement of phosphoinositide 3-kinase activity. These alterations were accompanied by higher GLUT4 content in the plasma membrane and alterations in the actin cytoskeleton dynamics. These data suggest that early postnatal undernutrition impairs insulin sensitivity in adulthood by promoting changes in critical steps of insulin signaling in adipose tissue, which may contribute to permanent changes in glucose homeostasis.
Garcia-Souza
Erica Patrícia
EP
Departament of Pharmacology, Institute of Biology, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, 20551-030, Brasil.
da Silva
Simone Vargas
SV
Félix
Gisele Barreto
GB
Rodrigues
Ananda Lages
AL
de Freitas
Marta Sampaio
MS
Moura
Aníbal Sanchez
AS
Barja-Fidalgo
Christina
C
D017667:Adipocytes / Q000378:metabolism* / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002469:Cell Separation; D002867:Chromones / Q000494:pharmacology; D018753:Diet, Protein-Restricted; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007774:Lactation / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D053778:Thiazolidines / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002867:Chromones; D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009025:Morpholines; C495694:Slc2a4 protein, rat; D053778:Thiazolidines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D014443:Tyrosine; D011494:Protein Kinases; C546845:mTOR protein, rat; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases; D005947:Glucose; C037068:latrunculin B; D020123:Sirolimus