The Role of Adipocyte XBP1 in Metabolic Regulation during Lactation

The adipocyte is central to organismal metabolism and exhibits significant functional and morphological plasticity during its formation and lifespan. Remarkable transformations of this cell occur during obesity and lactation, and thus it is essential to gain a better understanding of adipocyte function in these two metabolic processes. Considering the critical importance of the cellular organelle endoplasmic reticulum (ER) in adapting to fluctuations in synthetic processes, we explored the role of XBP1, a central regulator of ER adaptive responses, in adipocyte formation and function. Unexpectedly, deletion of adipocyte-XBP1 in vivo in mice (XBP1ΔAd) had no effect on adipocyte formation or on systemic homeostatic metabolism in mice fed a a regular or high-fat diet. However, during lactation, XBP1ΔAd dams displayed increased adiposity, decreased milk production, and decreased litter growth as compared with control dams. Moreover, we demonstrate that XBP1 is regulated during lactation and responds to prolactin to alter lipogenic gene expression. These results demonstrate a role for adipocyte-XBP1 in the regulation of lactational metabolism. [Display omitted] [Display omitted] •Adipocyte-specific deletion of XBP1 does not affect metabolic homeostasis in mice•Adipocytes regulate lactational metabolism through XBP1•XBP1ΔAd mice have increased fat mass and decreased pup weight, and produce less milk•Prolactin stimulates adipocyte XBP1 and negatively regulates lipogenic gene expression The adipocyte is poised to act at the intersection of energy supply and demand. Because of its extreme plasticity, it can expand in obesity or regress during starvation and lactation. How tissues crosstalk in the delicate balance of metabolism is an important question that remains unanswered. In this study, Hotamisligil and colleagues report that adipocytes can control the directional metabolism of lactation, introducing a new context in which to study the biology of these cells and how they regulate milk production.