Novel secreted regulators of glucose and lipid metabolism in the development of metabolic diseases – published online 24/08/2024

Lianna W. Wat and Katrin J. Svensson

The tight regulation of energy metabolism is crucial to health and survival. Secreted factors are one key class of regulators that control this process. Approximately 9% of the human genome, or 1891 genes, encode secreted products yet only a small percentage of these have been characterised and linked to metabolism. Recent advances in open-source expression data and proteomic techniques have led to rapid identification of new metabolic secreted factors. In this issue, Wat and Svensson (https://doi.org/10.1007/s00125-024-06253-x) summarise the last decade of discoveries of novel secreted factors or functions of previously known secreted factors that control glucose and lipid metabolism. Specifically, they discuss three secreted factors that promote the development of metabolic disease (scEMC10, vimentin and CILP2) and four secreted factors that are proposed to be protective (ISM1, LCN2, NRG1 and NRG4). This review highlights the most recent insights into understanding how the secretome contributes to metabolic regulation and discusses the current challenges of functional characterisation and therapeutic development. The figures from this review are available as a downloadable slideset.