A. Toward an animal model of childhood-onset obesity: follow-up of OLETF rats during pregnancy and lactation. Am J Physiol Regul Integr Comp Physiol 296: R224 -R232, 2009. First published November 26, 2008 doi:10.1152/ajpregu.90697.2008.-The Otsuka LongEvans Tokushima Fatty (OLETF) rat model of obesity (a spontaneous CCK1 receptor knockout) has been extensively studied as model of hyperphagia-induced obesity. In previous studies, young OLETF rats presented abnormal eating patterns [compared with Long-Evans Tokushima Otsuka (LETO) controls] in a variety of independent ingestion and nursing tests during the suckling period. The aim of the present study was to characterize the early emergence of abnormal adiposity in the pups. Moreover, because both the dams and the pups present the genetic mutation, a close follow-up of the dams' body weight and intake during pregnancy and lactation was performed to examine the circumstances that contribute to build up the pups' early adiposity. Compared with controls, OLETF pups presented higher fat levels, larger adipocytes, and increased waist circumference as early as postnatal day 7 and this profile persisted to the age of weaning. While LETO dams gained weight throughout pregnancy and lactation, OLETF dams were obese and hyperphagic during pregnancy but lost weight during lactation, probably as a result of rearing hyperphagic pups. Current and previous results suggest a possible influence of the dams' obesity during gestation and a high investment in nursing time during lactation on the pups' obesity levels during childhood. This, combined with the innate hyperphagia repeatedly observed in the pups at these early ages, makes the OLETF strain a useful tool in the research of childhood-onset obesity.overeating; animal models; gestation; feeding OBESITY IS A GROWING PUBLIC health concern that has reached epidemic proportions in Western societies in the last few decades (27). Although much research has already been conducted on obesity by using animal models, investigations have usually focused on adult males, leaving a gap regarding childhood and female obesity. In many cases, early symptoms can be detected during "preobese" stages, where interventions could be more successful in reaching perdurable outcomes. Given the permanent upward resetting of body weight set point that takes place when genetically predisposed individuals become obese, the identification of the early factors that can help understand and prevent obesity might be the key to control the spread of the obesity epidemic (1,5,6,33,36).Maternal obesity during pregnancy and lactation have been found to influence the offspring in the long term, predisposing them to develop larger fat pads and higher leptin and glucose levels later in life, especially in the presence of a genetic tendency (23, 30). Maternal obesity can also predispose offspring to obesity for generations to come (15,47). In a study on mice, females fed a palatable obesogenic diet throughout pregnancy and lactation produced obese offspring presenting...