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Unformatted text preview: REVIEW Gestational programming of offspring obesity/hypertension DONALD A. NOVAK 1 , MINA DESAI 2 , & MICHAEL G. ROSS 2 1 Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA, and 2 Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Geffen School of Medicine at UCLA, CA, USA (Received 16 January 2006; accepted 20 March 2006) Abstract The intrauterine milieu impacts fetal growth directly during gestation. It is now clear, however, that postnatal phenotype is also influenced by prenatal conditions. A variety of disorders in the adult have been linked to fetal size at birth; these include glucose intolerance, cardiovascular disease, and the subjects of this review, obesity and hypertension. We will review recent data regarding these associations and the pathophysiologic mechanisms underlying them in humans as well as in animal models. Keywords: Obesity, hypertension, IUGR, development, fetal origins Introduction Over the past fifteen years, correlations between size at birth and a variety of adult onset conditions in- cluding insulin resistance [1,2], hypertension [3,4], cardiovascular disease  including stroke , and perhaps breast cancer  and atopy , have been demonstrated. While a variety of factors may be associated with infants born small, suboptimal pre- and perinatal nutrition, either as a primary insult or secondary to genetic or underlying or coincident maternal disease, has been demonstrated to play an important role both in animal models and in humans. The current review will highlight recent evidence as it pertains to perinatal determinants of eventual adult obesity and hypertension in infants born small. Obesity and the thrifty hypothesis Obesity is a complex disorder, influenced strongly by both genetics (i.e., melanocortin 4 receptor mutations) and environment [9,10]. The influence of birth weight on subsequent adult obesity repre- sents a J or U shaped curve, with an increased incidence at both extremes. In the human, obese mothers are more likely to deliver relatively large infants who have a significant risk of subsequent obesity [11,12]. Paradoxically, infants born small also have an enhanced risk of subsequent obesity. Indeed, a variety of work has demonstrated that human infants born small who during childhood gain weight rapidly (catch-up growth) are at greater risk of developing central obesity and metabolic syn- drome as they age . The thrifty hypothesis posits that suboptimal early nutrition results in fetal/neonatal metabolic adaptations designed to allow the organism to develop efficiently in a nutrient-poor environment. Subsequent exposure to a nutrient-rich environment postnatally then results in untoward consequences, including the development of type 2 diabetes and the metabolic syndrome [16,17]. Indeed, women exposed in utero to famine early in gestation had a higher incidence of obesity at age 50 than did those not exposed to nutrient deprivation . The in-not exposed to nutrient deprivation ....
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This note was uploaded on 11/26/2010 for the course IB 35AC taught by Professor Hlusko during the Spring '08 term at University of California, Berkeley.
- Spring '08
- The Land