Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition.
Environmental factors and diet are generally believed to be accelerators of obesity and hypertension, but they are not the underlying cause. Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming. Using fetal undernutrition throughout pregnancy, we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease. Virgin Wistar rats were time mated and randomly assigned to receive food either ad libitum (AD group) or at 30% of ad libitum intake, or undernutrition (UN group). Offspring from UN mothers were significantly smaller at birth than AD offspring. At weaning, offspring were assigned to one of two diets [a control diet or a hypercaloric (30% fat) diet]. Food intake in offspring from UN mothers was significantly elevated at an early postnatal age. It increased further with advancing age and was amplified by hypercaloric nutrition. UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations. This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology. We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia, obesity, and hypertension as a consequence of altered fetal development.
Vickers
M H
MH
Research Centre for Developmental Medicine and Biology, Faculty of Medicine and Health Science, University of Auckland, 92019 Auckland, New Zealand.
Breier
B H
BH
Cutfield
W S
WS
Hofman
P L
PL
Gluckman
P D
PD
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001724:Birth Weight; D001794:Blood Pressure; D004435:Eating; D002149:Energy Intake; D005215:Fasting / Q000097:blood; D005260:Female; D005333:Fetus / Q000502:physiology*; D006963:Hyperphagia / Q000209:etiology*; D006973:Hypertension / Q000209:etiology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D009748:Nutrition Disorders / Q000150:complications; D009765:Obesity / Q000209:etiology*; D011247:Pregnancy; D011248:Pregnancy Complications; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D020738:Leptin