Diet-induced modifications to milk composition have long-term effects on offspring growth in rabbits.

It has been clearly demonstrated that the maternal nutritional status during pregnancy and lactation has long-term effects on offspring health. In mammals, milk represents the first maternal support provided to the newborns so that its composition may play a major role in long-term programming. We therefore assessed the effects of maternal high-fat/high-sugar obesogenic (OD) or control (CD) diets on offspring growth and adiposity in the rabbit. Between 7 and 20 wk of age, the BW gain of OD milk-fed rabbits was higher than that of CD milk-fed rabbits ( < 0.05). Body fat mass measurements at 21 wk of age revealed a significant increase in body adiposity as a function of milk ingested during the neonatal period, in both female and male offspring ( < 0.05). A marked weight gain difference was observed according to the milk in both female and male offspring. Moreover, we investigated the composition in major proteins and leptin levels in milk from OD or CD diet-fed dams. Liquid chromatography-mass spectrometry analysis of individual CD skimmed milk samples enabled identification and quantification of the rabbit main milk proteins and of their main phosphorylated isoforms at 2 different stages of lactation (3 and 10 d). Here we show that the OD diet induced a reduction in the whey acidic protein content concomitantly with both an increase in serum albumin and lactoferrin contents and in the phosphorylated isoforms of the main milk proteins. Furthermore, a sharp rise in leptin levels was observed in the milk of OD diet-fed dams on Day 10 of lactation when compared with CD diet animals ( < 0.05). Taken together, these findings provide evidence that lactation is a critical window of development during which exposure to a deleterious diet is highly detrimental to long-term outcomes. Moreover, these insights suggest that it may be possible to prevent at least some of the adverse effects of inadequate maternal nutrition on the long-term metabolic outcomes of the offspring through nutritional interventions applied during the lactation period.

Milk from dams fed an obesogenic diet combined with a high-fat/high-sugar diet induces long-term abnormal mammary gland development in the rabbit.

Alterations to the metabolic endocrine environment during early life are crucial to mammary gland development. Among these environmental parameters, the initial nutritional event after birth is the consumption of milk, which represents the first maternal support provided to mammalian newborns. Milk is a complex fluid that exerts effects far beyond its immediate nutritional value. The present study, therefore, aimed to determine the effect of the nutritional changes during the neonatal and prepubertal periods on the adult mammary phenotype. Newborn rabbits were suckled by dams fed a high-fat/high-sugar obesogenic (OD) or a control (CON) diet and then subsequently fed either the OD or CON diets from the onset of puberty and throughout early pregnancy. Mammary glands were collected during early pregnancy (Day 8 of pregnancy). Rabbits fed with OD milk and then subjected to an OD diet displayed an abnormal development of the mammary gland: the mammary ducts were markedly enlarged (P < 0.05) and filled with abundant secretory products. Moreover, the alveolar secretory structures were disorganized, with an abnormal aspect characterized by large lumina. Mammary epithelial cells contained numerous large lipid droplets and exhibited fingering of the apical membrane and abnormally enlarged intercellular spaces filled with casein micelles. Leptin has been shown to be involved in modulating several developmental processes. We therefore analyzed its expression in the mammary gland. Mammary leptin mRNA was strongly expressed in rabbits fed with OD milk and subjected to an OD diet by comparison with the CON rabbits. Leptin transcripts and protein were localized in the epithelial cells, indicating that the increase in leptin synthesis occurs in this compartment. Taken together, these findings suggest that early-life nutritional history, in particular through the milking period, can determine subsequent mammary gland development. Moreover, they highlight the potentially important regulatory role that leptin may play during critical early-life nutritional windows with respect to long-term growth and mammary function.