title: Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype.
abstract: We have previously shown that artificial rearing of newborn female rat pups on a high-carbohydrate (HC) milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype) and that the maternal HC phenotype was transmitted to their progeny (2-HC rats) because of fetal development in the HC female rat. The aims of this study were to investigate 1) the fetal adaptations that predisposed the progeny for the expression of the HC phenotype in adulthood and 2) whether the transfer of the HC phenotype to the progeny could be reversed by maternal food restriction. Fetal parameters such as plasma insulin and glucose levels, mRNA level of preproinsulin gene, pancreatic insulin content, and islet insulin secretory response in vitro were determined. On gestational day 21, 2-HC fetuses were hyperinsulinemic, had increased insulin content and mRNA level of the preproinsulin gene in their pancreata and demonstrated an altered glucose-stimulated insulin secretory response by isolated islets. Modification of the intrauterine environment in HC female rats was achieved by pair feeding them to the amount of diet consumed by age-matched control rats from the time of their weaning. This mild dietary restriction reversed their HC phenotype and also prevented the development of the HC phenotype in their progeny. These findings show that mal-programming of the progeny of the hyperinsulinemic-obese HC female for the expression of the HC phenotype is initiated in utero and that normalization of the maternal environment in HC female rats by mild food restriction resulted in the normal phenotype in their progeny.
authors.affiliation: Dept. of Biochemistry, School of Medicine and Biomedical Sciences, SUNY-Buffalo, Buffalo, NY 14214, USA.
authors.forename: Malathi
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Aalinkeel
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.forename: Paul
authors.initials: P
authors.lastname: Mitrani
authors.forename: Jignesh D
authors.initials: JD
authors.lastname: Pandya
authors.forename: Brenda
authors.initials: B
authors.lastname: Strutt
authors.forename: David J
authors.initials: DJ
authors.lastname: Hill
authors.forename: Mulchand S
authors.initials: MS
authors.lastname: Patel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000494:pharmacology; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006946:Hyperinsulinism / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007930:Leucine / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011384:Proinsulin / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000235:genetics
chemical_list: D001120:Arginine; D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D005947:Glucose; D051542:Hepatocyte Nuclear Factor 3-beta; D018398:Homeodomain Proteins; D007328:Insulin; D007930:Leucine; D008055:Lipids; D011384:Proinsulin; D011498:Protein Precursors; D012333:RNA, Messenger; D015534:Trans-Activators; C490555:Neurod1 protein, rat; C084010:pancreatic and duodenal homeobox 1 protein; C013737:preproinsulin