**1. Introduction**

Adverse environmental conditions during the intrauterine period increase the risk to develop cardiometabolic diseases (CMD), a process known as fetal programming [1,2]. Exposure to the fetus to insufficient nutrients is one of the key programming factors, widely demonstrated in human populations by the association between low birth weight (LBW) and higher rates of hypertension, coronary heart disease, or type 2 diabetes mellitus [3–5]. Fetal programming has also been validated in animal models [6–8]. The postnatal period seems to be a second critical window for programming, particularly after exposure to a fetal stressor. During this period, LBW individuals frequently experience a rapid weight gain, and compelling evidence indicates that this growth pattern is also deleterious. Adolescents born prematurely with a quick postnatal growth have a lower flow-mediatedendothelial dilatation compared to those with slower weight gain and a higher risk of hypertension [8]; quick growth and elevated central adiposity in infancy also contribute to the future development of metabolic disorders [9,10]. A systematic review highlights that rapid postnatal catch-up growth is a more important factor than LBW alone for the development of cardiovascular disease and its risk factors [11].

Nutrition in LBW individuals represents a challenge to ensure a postnatal growth pattern adequate to achieve brain and bone development while preventing CMD [12]. In this context, the lactation period has been proposed as a critical window to counteract alterations initiated during fetal life [13], since human breast milk is recognized as the gold standard for infant nutrition tailored to provide the nutrients and bioactive factors for healthy growth [14]. Breastfeeding provides protection against CMD, is associated with lower blood pressure levels and a lower risk of overweight in children [15,16], and a systematic review evidences slower rates of weight gain in preterm and LBW infants fed with breastmilk compared to the formula [17].

Animal models provide the tools to analyze the influence of both intrauterine and lactation periods in a controlled environment. In a rat model of fetal programming induced by maternal undernutrition during gestation (MUN), we have demonstrated that LBW offspring accelerate growth during lactation, reaching the same body weight as control counterparts by wearing. This catch-up trajectory in MUN rats leads to excessive growth of cardiovascular organs in males [18,19] and white adipose tissue (WAT) deposits in both sexes [20].

In this study, we aim to demonstrate in an animal model of LBW if a slower growth during the lactation period can rescue the cardiometabolic alterations induced by undernutrition. To test this hypothesis, in MUN rats we have modified the lactation environment using a cross-fostering protocol and analyzed the impact on (1) body weight and length growth pattern during the first three weeks of postnatal life, (2) milk macronutrient composition, and (3) heart, aorta and perivascular adipose tissue growth and cardiac function at weaning, assessing the influence of sex in the abovementioned parameters.
