title: Low birth weight male guinea pig offspring display increased visceral adiposity in early adulthood.
abstract: Uteroplacental insufficiency (UPI)-induced intrauterine growth restriction (IUGR) predisposes individuals to adult visceral obesity. We postulated that low birth weight (LBW) offspring, from UPI-induced IUGR pregnancies, would display a visceral adipose lipogenic molecular signature involving altered gene expression, phosphorylation status of proteins of the lipid synthesis pathway and microRNA (miR) expression profile, occurring in association with increased visceral adiposity. Normal birth weight (NBW) and LBW (obtained by uterine artery ablation) male guinea pig pups were fed a control diet from weaning to 145 days and sacrificed. Despite being lighter at birth, LBW pups displayed body weights similar to NBW offspring at 145 days. At this age, which represents young adulthood, the relative weights of LBW epididymal white adipose tissue (EWAT) and lipid content were increased; which was consistent with adipocyte hypertrophy in the LBW offspring. Additionally, the mRNA expression of lipid synthesis-related genes including acetyl-CoA carboxylase 1 (ACC1), diglyceride acyltransferase 2 (DGAT2) and peroxisome proliferator-activated receptor gamma 1 (PPARγ1), was increased in LBW EWAT. Further, LBW EWAT displayed decreased phospho-ACC (Ser79) and phospho-PPARγ (Ser273) proteins. Moreover, the mRNA expression of hormone-sensitive lipase (HSL) and fatty acid binding protein 4 (FABP4), both involved in promoting adipose lipid storage, was increased in LBW EWAT. Finally, miR-24 and miR-103-2, miRs related to adipocyte development, were both increased in LBW EWAT. These findings indicate that, following an adverse in utero environment, lipid synthesis-related genes and miR expression, along with phosphorylation status of key regulators of lipid synthesis, appear to be chronically altered and occur in association with increased visceral adiposity in young adult IUGR male offspring.
authors.affiliation: Department of Obstetrics and Gynecology, Children's Health Research Institute, Lawson Health Research Institute, Western University, London, Ontario, Canada.
authors.forename: Ousseynou
authors.initials: O
authors.lastname: Sarr
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Thompson
authors.affiliation: Department of Obstetrics and Gynecology, Children's Health Research Institute, Lawson Health Research Institute, Western University, London, Ontario, Canada.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Departments of Medical Imaging, Medical Biophysics, and Oncology, Western University, London, Ontario, Canada; Lawson Imaging, Lawson Health Research Institute, London, Ontario, Canada; Robarts Research Institute, London, Ontario, Canada.
authors.forename: Ting-Yim
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Children's Health Research Institute, Lawson Health Research Institute, Western University, London, Ontario, Canada; Department of Physiology and Pharmacology, Western University, London, Ontario, Canada.
authors.forename: Timothy R H
authors.initials: TR
authors.lastname: Regnault
mesh_terms: D000818:Animals; D001724:Birth Weight; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D056128:Obesity, Abdominal / Q000235:genetics / Q000378:metabolism*; D010927:Placental Insufficiency / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D035683:MicroRNAs