Published online before print December 17, 2007, doi: 10.1161/HYPERTENSIONAHA.107.101477
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(Hypertension. 2008;51:383.)
© 2008 American Heart Association, Inc.
Original Articles |
Diet-Induced Obesity in Female Mice Leads to Offspring Hyperphagia, Adiposity, Hypertension, and Insulin Resistance
A Novel Murine Model of Developmental Programming
From the Division of Reproduction & Endocrinology (A.-M.S., P.A.M., M.A., M.R.C., J.M.M., L.P., P.D.T.) and Applied Biomedical Research Group (A.R.), King’s College London, UK; the Laboratory for Health Protection Research (E.H.J.M.J., A.H.P.), National Institute for Public Health and the Environment, Bilthoven, Netherlands; the Department of Clinical Biochemistry (S.E.O., D.F.T.), University of Cambridge, UK; and the Institute of Life Sciences (C.R.), Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
Correspondence to Dr Paul Taylor, Division of Reproduction & Endocrinology, Kings College London, 10th Floor North Wing, St Thomas’ Hospital, London SE1 7EH, UK. E-mail paul.taylor{at}kcl.ac.uk
Maternal obesity is increasingly prevalent and may affect the long-term health of the child. We investigated the effects of maternal diet-induced obesity in mice on offspring metabolic and cardiovascular function. Female C57BL/6J mice were fed either a standard chow (3% fat, 7% sugar) or a palatable obesogenic diet (16% fat, 33% sugar) for 6 weeks before mating and throughout pregnancy and lactation. Offspring of control (OC) and obese dams (OO) were weaned onto standard chow and studied at 3 and 6 months of age. OO were hyperphagic from 4 to 6 weeks of age compared with OC and at 3 months locomotor activity was reduced and adiposity increased (abdominal fat pad mass; P<0.01). OO were heavier than OC at 6 months (body weight, P<0.05). OO abdominal obesity was associated with adipocyte hypertrophy and altered mRNA expression of β-adrenoceptor 2 and 3, 11βHSD-1, and PPAR-
2. OO showed resistance artery endothelial dysfunction at 3 months, and were hypertensive, as assessed by radiotelemetry (nighttime systolic blood pressure at 6 months [mm Hg] mean±SEM, male OO, 134±1 versus OC, 124±2, n=8, P<0.05; female OO, 137±2 versus OC, 122±4, n=8, P<0.01). OO skeletal muscle mass (tibialis anterior) was significantly reduced (P<0.01) OO fasting insulin was raised at 3 months and by 6 months fasting plasma glucose was elevated. Exposure to the influences of maternal obesity in the developing mouse led to adult offspring adiposity and cardiovascular and metabolic dysfunction. Developmentally programmed hyperphagia, physical inactivity, and altered adipocyte metabolism may play a mechanistic role.
Key Words: obesity • pregnancy • developmental programming • metabolic syndrome • appetite • blood pressure • mouse
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