Switching off the furnace: brown adipose tissue and lactation.

Abstract

In rodents, brown adipose tissue (BAT) is dynamically regulated by reproductive state, with greater thermogenic activity and capacity outside reproduction and subsequent downregulation of the tissue machinery and function during lactation. We argue that the main reason for BAT to be shut down is the competition between lactogenic (associated with milk synthesis) and thermogenic (associated with BAT activity) heat production within a limited scope for heat dissipation, rather than to spare glucose and lipids for milk production. To add dimension to this competition, we calculate the contribution of lactogenic and thermogenic heat production to daily energy expenditure in mice and estimate the mass-specific heat production in both BAT and mammary glands as 383 and 49\u202fW per kg of tissue, respectively. We have also extracted the original data on BAT characteristics during lactation from 59 papers published over the last four decades and evaluate the direction and magnitude of the changes in various parameters used to describe BAT activity and function across different studies. On average, BAT function during lactation is downregulated by ∼50% when compared with females outside reproduction, both in vivo and in vitro. The level of this downregulation depends on milk production, suggesting the functional link between BAT and mammary glands. Although BAT during lactation responds to various experimental manipulations, these responses are typically reduced to ∼50% of the absolute values achieved outside reproduction, with insulin and noradrenaline resistance being the hallmarks of BAT reduced responsiveness. Unlocking the mechanisms underlying the natural cycles of BAT function and depression during lactation may identify molecular pathways that are important to target when attempts are made to activate BAT in humans.