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

Date Published: December 17, 2015

Publisher: Public Library of Science

Author(s): Yuriy Nozhenko, Madhu Asnani-Kishnani, Ana M. Rodríguez, Andreu Palou, Eric M Mintz.


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.

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The association between numerous chronic diseases, including obesity, with early nutrition (both during the prenatal and postnatal periods) has been established, and is related to the term metabolic “programming” [1–3], where the role of key components such as hormones during the early period of development may be key in pre-programing brain development and body functions, thus influencing the risk for diseases in the adulthood [4]. In this sense, many studies indicate that breastfeeding protects against the development of obesity and related disorders in later life [5], and the search of the possible milk components responsible of this protective effects is a focus of interest.

The first question formulated in this work was the possible existence of daily rhythms in the levels of leptin and other two important hormones present in mammalian milk (ghrelin and adiponectin) and the answer is that we have found rhythms in the three hormones in milk, but not daily, since they have a period of about half a day, and only at the earliest phase of lactation (day 5 in our study) (Figs 1–3). This period of about half a day (12h) suggests that these rhythms at day 5 fit with a circasemidian pattern, and the possibility that they may be controlled by circadian clocks arises, as reported by other authors for other molecules and tissues [41], an interesting point that would deserve more research. Moreover, the highest positive correlation between milk and dam´s plasma levels of leptin and adiponectin is shown at day 5 (Table 1), and even for ghrelin day 5 is the only day where there is a correlation (also positive). Although both leptin and adiponectin milk levels are still positively correlated with their plasma levels in dams at days 10 and 15 (Tables 2 and 3), this level of correlation is lower; moreover, at day five the shape of the curve for the three hormones in milk is someway similar to the shape of the curve representing the plasma levels (Figs 1A, 2A and 3A). Hence, the results suggest that at the earliest phase of lactation is when the milk levels of leptin, ghrelin and adiponectin can be more dependent on their circulating levels in the dams, but only in part, since we observe significant rhythmicity only in the milk levels which is nor present in the circulating levels. Moreover, this can be put into context for each hormone as following.

In summary, we describe here the existence of rhythms in the hormone concentration, with a period around half a day, of milk leptin, and also ghrelin and adiponectin, only at the early phase of lactation, a new knowledge that is important and that may have a significant influence in the development of the progeny. The possibility that these rhythms may be related with circasemidian rhythms in the pups may not be ruled out and it may deserve more research. We also describe the existence of a “milk leptin surge” around mid-lactation (day 10) which may be important for the known leptin surge described in the circulation of pups and also crucial in the development of pups and metabolic programming. The biological rhythms of leptin and other milk hormones such as ghrelin and adiponectin should be taken into account in future research and applications, since it may influence the development of formula milks adapted to the phase of lactation (e.g. in early lactation) that could take into account the possibility of biological rhythms in key milk hormones.