The Role of Adipocyte XBP1 in Metabolic Regulation during Lactation

• 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

SummaryThe 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.Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MOV filesOptionsDownload video (30697 K)

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