biostudies-literatureUnknownMintz RLNIAID NIH HHSNCI NIH HHSNIH HHSThe omentum, a specialized adipose tissue within the peritoneum, is a primary niche for ovarian cancer (OC) dissemination during peritoneal carcinomatosis. Traditionally, omental adipocytes are thought to promote OC growth by supplying lipids, supported by evidence that global FABP4 deficiency reduces tumor progression. Here, we generated mice lacking mature adipocytes in the peritoneum, including the omentum. ID8p53^-/-Brca2^-/-, BPPNM, and KPCA OC cells retained a propensity to seed regions typically associated with adipocytes, even without mature adipocytes. However, the lack of mature adipocytes did not suppress peritoneal OC expansion, whereas removing the adipocyte-free omentum did. Murine and human single-cell RNA sequencing revealed that endothelial FABP4 was high in the omentum. Indeed, endothelial cell-selective deficiency of FABP4 reduced OC growth in the peritoneum. These findings prompt a reevaluation of adipocyte contributions to OC progression and suggest a key role of the omental vasculature in supporting OC metabolic growth.bioRxiv : the preprint server for biology2025.10.28.685098https://www.ebi.ac.uk/biostudies/studies/S-EPMC12636596biostudies-literatureAdipocytes are dispensable in shaping the ovarian cancer tumor microenvironment in the omentum.PMC12636596P30 CA091842S10 OD027042R01 CA258325R37 AI049653K00 CA264434Yiew NKHZinselmeyer BHMorris SAButka EGKim ARandolph GJWohltmann MZhang NNing SGallerand AMintz RLHan JZou WfalseAdipocytes are dispensable in shaping the ovarian cancer tumor microenvironment in the omentum.The omentum, a specialized adipose tissue within the peritoneum, is a primary niche for ovarian cancer (OC) dissemination during peritoneal carcinomatosis. Traditionally, omental adipocytes are thought to promote OC growth by supplying lipids, supported by evidence that global FABP4 deficiency reduces tumor progression. Here, we generated mice lacking mature adipocytes in the peritoneum, including the omentum. ID8p53^-/-Brca2^-/-, BPPNM, and KPCA OC cells retained a propensity to seed regions typically associated with adipocytes, even without mature adipocytes. However, the lack of mature adipocytes did not suppress peritoneal OC expansion, whereas removing the adipocyte-free omentum did. Murine and human single-cell RNA sequencing revealed that endothelial FABP4 was high in the omentum. Indeed, endothelial cell-selective deficiency of FABP4 reduced OC growth in the peritoneum. These findings prompt a reevaluation of adipocyte contributions to OC progression and suggest a key role of the omental vasculature in supporting OC metabolic growth.2025-01-01T00:00:00Z2025 Oct2026-06-11T03:09:46.962Z2026-06-11T03:07:45.868ZS-EPMC126365964127987110.1101/2025.10.28.685098