title: Maternal nutritional programming of fetal adipose tissue development: long-term consequences for later obesity.
abstract: As obesity reaches epidemic levels in the United States there is an urgent need to understand the developmental pathways leading to this condition. Obesity increases the risk of hypertension and diabetes, symptoms of which are being seen with increased incidence in children. Adipocyte development begins in the fetus and, in contrast to all other tissues whose growth ceases in late juvenile life, it has the capacity for "unlimited" growth. In normal healthy individuals, the increase in fat mass with age is accompanied by a parallel increase in cortisol sensitivity, i.e., increased glucocorticoid receptor abundance and increased activity of the enzyme 11beta hydroxysteroid dehydrogenase type 1. Enhanced adipocyte sensitivity to cortisol is promoted in offspring born to mothers that were nutrient-restricted in utero in conjunction with increased peroxisome proliferator activated receptor alpha. This adaptation only appears to be associated with greater fat mass in the offspring when maternal nutrient restriction is confined to late gestation, coincident with the period of maximal fetal growth. In these offspring, increased fat mass is accompanied by glucose intolerance and insulin resistance, in conjunction with an adipose tissue specific reduction in glucose transporter 4 abundance. In conclusion, changes in maternal and, therefore, fetal nutrient supply at specific stages of gestation have the potential to substantially increase the risk of those offspring becoming obese in later life. The extent to which changes in dietary habits, both during pregnancy and in later life, may act to contribute to the current explosion in childhood and adult obesity remains a scientific and public health challenge to us all.
authors.affiliation: Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Budge
authors.forename: Mo G
authors.initials: MG
authors.lastname: Gnanalingham
authors.forename: David S
authors.initials: DS
authors.lastname: Gardner
authors.forename: Alison
authors.initials: A
authors.lastname: Mostyn
authors.forename: Terence
authors.initials: T
authors.lastname: Stephenson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Symonds
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000196:embryology* / Q000473:pathology; D000818:Animals; D004032:Diet; D005260:Female; D047109:Fetal Development; D018149:Glucose Intolerance / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007333:Insulin Resistance; D008954:Models, Biological; D009035:Mothers; D009765:Obesity / Q000209:etiology*; D047493:PPAR alpha / Q000378:metabolism; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047493:PPAR alpha; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone