Prenatal Stress or High-Fat Diet Increases Susceptibility to Diet-Induced Obesity in Rat Offspring

Prenatal Stress or High-Fat Diet Increases Susceptibility to Diet-Induced Obesity in Rat Offspring Kellie L.K. Tamashiro 1 , Chantelle E. Terrillion 1 , Jayson Hyun 1 , James I. Koenig 2 and Timothy H. Moran 1 1 Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland; 2 Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland. Corresponding author: Kellie L.K. Tamashiro, ktamashiro{at}jhmi.edu . Abstract OBJECTIVE Perturbations to the prenatal environment have been associated with the development of adult chronic disease, findings that gave rise to the “Barker Hypothesis” or the “developmental origins of adult disease” concept. In this study, we used an animal model to determine the metabolic consequences of maternal prenatal stress and high-fat feeding on the developing offspring. RESEARCH DESIGN AND METHODS Pregnant female Sprague-Dawley rats were maintained on standard chow or 60% high-fat diet throughout gestation and lactation. Half of each group were exposed to a novel variable stress paradigm during the 3rd week of gestation, whereas control dams were left undisturbed. Body weight, body composition, glucose tolerance, and endocrine parameters were measured in offspring through early adulthood. RESULTS Male and female pups from dams that experienced prenatal stress and/or were on a high-fat diet weighed more beginning on postnatal day 7 compared with standard chow–control pups. Access to high-fat diet at weaning increased the body weight effect through early adulthood and was attributable to greater adiposity. Pups weaned onto standard chow diet showed no significant difference in glucose clearance or insulin secretion. However, pups weaned onto high-fat diet had impaired glucose tolerance if their dams were on a high-fat diet, experienced prenatal stress, or both. CONCLUSIONS Our data demonstrate that prenatal stress and/or high-fat diet during the intrauterine or postnatal environment affects offspring in a manner that increases their susceptibility to diet-induced obesity and leads to secondary adverse metabolic consequences. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received August 19, 2008. Accepted January 20, 2009. Readers may use this article as l