title: Embryo-transfer of the F2 postnatal calorie restricted female rat offspring into a control intra-uterine environment normalizes the metabolic phenotype.
abstract: OBJECTIVE
  Postnatal calorie and growth restriction (PNGR) in the first generation (F1) rat female offspring causes a lean and glucose tolerant phenotype associated with hypoinsulinemia and reduced glucose-stimulated insulin secretion (GSIS). Despite the absence of gestational hyperglycemia in the F1 PNGR female, naturally born second generation (F2) PNGR female adult offspring reportedly exhibit obesity, hyperglycemia with insulin resistance. The objective of this study was to determine the role of the intrauterine environment on the heritability of the trans-generational phenotypic expression in the F2 PNGR female adult offspring.
  
  
  METHODS
  We performed embryo transfer (ET) of the F2 embryos from the procreating F1 pregnant PNGR or control (CON) females to gestate in control recipient rat mothers. Employing stable isotopes glucose metabolic kinetics was determined.
  
  
  RESULTS
  Birth weight, postnatal growth pattern and white adipose tissue in female F2 ET-PNGR were similar to ET-CON. Similarly, no differences in basal glucose and insulin concentrations, GSIS, glucose futile cycling and glucose clearance were seen. When compared to F2 ET-CON, F2 ET-PNGR showed no overall difference in glucose or hepatic glucose production (HGP) AUCs with minimal hyperglycemia (p<0.04) as a result of unsuppressed endogenous HGP (p<0.02) observed only during the first phase of IVGTT.
  
  
  CONCLUSIONS
  We conclude that the lean, glucose tolerant and hypoinsulinemic phenotype with reduced GSIS in the F1 generation is nearly normalized when the embryo-transferred F2 offspring gestates in a normal metabolic environment. This observation supports a role for the intra-uterine environment in modifying the heritability of the trans-generational PNGR phenotype.
authors.affiliation: Department of Pediatrics, Division of Neonatology and Developmental Biology and Neonatal Research Center, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1752, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Garg
authors.forename: Manikkavasagar
authors.initials: M
authors.lastname: Thamotharan
authors.forename: Yun
authors.initials: Y
authors.lastname: Dai
authors.forename: Paul W N
authors.initials: PW
authors.lastname: Lee
authors.forename: Sherin U
authors.initials: SU
authors.lastname: Devaskar
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000378:metabolism*; D019540:Area Under Curve; D001724:Birth Weight / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D004624:Embryo Transfer; D005260:Female; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin