Milk Leptin Surge and Biological Rhythms of Leptin and Other Regulatory Proteins in Breastmilk

Abstract

A significant number of chronic diseases are linked to perinatal nutrition, and prevention may be associated to naturally occurring components of breast milk. One key hormone in breast milk is leptin, related with the protection from obesity in the adulthood, thus knowing its changes through the day or lactation is crucial. We aimed to investigate the daily rhythms in the milk levels of leptin, together with other two related hormones, ghrelin and adiponectin, during lactation (days 5, 10 and 15) in rat dams, and the relation with morphometric parameters (dams and pups). Summarizing the main results, the existence of biological rhythms, but not daily and maybe circasemidian, was confirmed for the three hormones at the earliest period of lactation. The correlations performed generally showed a possible dependence of milk hormone levels on plasma levels at the early phase of lactation, while with the progression of lactation this dependence may fade and the hormone levels are suggested to be more dependent on mammary gland production/maturation. There was also a correlation between milk leptin and adiponectin levels, especially in the first half of lactation, suggesting a possible parallel regulation. Interestingly, we describe a milk leptin surge around the mid of lactation (at day 10) which may be related with pup´s growth (males and females) and with the well-known (in the literature) plasma leptin surge in pups. All this knowledge may be crucial for future applications in the development of formula milk and in relation with the role of leptin surge during lactation.

Relationship of Maternal Weight Status Before, During, and After Pregnancy with Breast Milk Hormone Concentrations

“…Our results confirmed this association in exclusively breastfeeding women and extended it by documenting that milk leptin concentration is responsive to dynamic aspects of weight change in pregnancy and lactation. Maternal serum leptin increases during late gestation and declines after parturition (the so‐called “leptin surge”), which is a phenomenon thought to be critical for maturation of appetite‐regulating centers in the fetal brain and which we saw reflected in a significant decline in milk leptin from 1 to 3 months. Milk leptin is thought to derive in large part from maternal serum, the level of which tracks changes in adiposity; this may explain why we found it to associate with maternal GWG and PPWL as well as BMI.…”

“…Milk leptin is thought to derive in large part from maternal serum, the level of which tracks changes in adiposity; this may explain why we found it to associate with maternal GWG and PPWL as well as BMI. It is not clear why the same results were not found for insulin or adiponectin, but it may relate to differences across hormones in the degree to which their appearance in milk occurs via active expression and/or transport by the mammary epithelial cells rather than passive paracellular diffusion (21,32). Serial measurement of maternal serum would help to address this point in future.…”

Sexually Dimorphic Associations between Maternal Factors and Human Milk Hormonal Concentrations

“…Other adipokines, such as adiponectin, are involved in the regulation of inflammatory processes and insulin sensitivity [26]. In experimental animal models, the presence of adipokines in HM has been linked to postnatal programming and may impact later metabolic health outcomes in the infant [5,27], including the development of obesity and metabolic syndrome later in life [28]. Nonetheless, with the exception of leptin, the concentration of these hormones in HM and the interplay between infant-maternal characteristics and HM composition remains poorly defined.…”

Long-lived weight-reduced αMUPA mice show higher and longer maternal-dependent postnatal leptin surge

“…And finally, leptin was not detectable in leptin-deficient (ob/ob) offspring of ob/+ dams [ 23 ]. Other studies, on the other hand, found that rat’s milk-borne leptin peaks at about the same day as the pups’ leptin surge [ 20 ]. Moreover, when recombinant leptin was supplied orally to suckling rats, it was absorbed through the stomach and contributed to their total circulating levels [ 17 – 19 ].…”

“…This surge is related, to a varying degree, to leptin’s mRNA expression levels in white and brown fat and in gastric epithelial cells, as well as to total fat mass [ 7 , 13 – 17 ]. Leptin surge was also suggested to be related to dam’s diet and milk-borne leptin levels [ 5 , 17 – 20 ], while others suggested that pups leptin level is rather related to the pup’s nutritional status [ 14 , 21 – 24 ]. Irrespective of leptin’s origin, previous studies have established that neonatal leptin acts as a developmental factor involved in rewiring hypothalamic circuits and peripheral organs involved in energy homeostasis [ 25 – 29 ].…”