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How mammals fuel milk production may have implications for cancer

s three times its total body weight in milk, which consists of lipid, protein, and lactose. To accomplish this, two distinct developmental programs must be executed: first, cells must proliferate and differentiate to form the structures that will ultimately serve as the site of milk synthesis, the researchers said. Second, mammary epithelial cells must coordinately activate multiple biosynthetic pathways—as well as deactivate pathways that break lipids down—in order to have the metabolic capacity to synthesize large quantities of milk.

Earlier studies by the researchers found that the protein kinase Akt1 rises in concentration during pregnancy and lactation, suggesting a potential developmental role for the kinase in milk production. Another study showed that permanent activation of Akt1 in the mammary glands of mice leads to early lipid accumulation during pregnancy, raising the possibility that the gene might be important in the increased synthetic demand for lipid during lactation.

To further investigate, in the current study, the researchers examined mice lacking either Akt1 or the related gene Akt2, which are expressed in the same areas of the mammary gland at distinct developmental stages. While Akt1 protein increases during pregnancy and lactation, Akt2 levels decline.

Indeed, the researchers found that the mammary gland cells of Akt1-deficient mice failed to engage critical metabolic pathways during the transition from pregnancy to lactation, which in turn led to other deficiencies. Specifically, the mammary cells failed to increase their uptake of glucose, cells?primary energy source, and their synthesis of lipid. The cells also did not lower the level of enzymes that break down lipids.

As early as two days after birth, pups nursed by mice lacking Akt1 weighed significantly less than those nursed by normal mothers. That difference in weight only grew more exaggerated with time. In contrast, the researchers reported,
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Source:Cell Press


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