@article{4b72eac3839d440a95ff63c7f1ed3d47,
title = "Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) patients display distinct phenotypes of cachexia development, with either adipose tissue loss preceding skeletal muscle wasting or loss of only adipose tissue. Activin A levels were measured in serum and analyzed in tumor specimens of both a cohort of Stage IV PDAC patients and the genetically engineered KPC mouse model. Our data revealed that serum activin A levels were significantly elevated in Stage IV PDAC patients in comparison to age-matched non-cancer patients. Little is known about the role of activin A in adipose tissue wasting in the setting of PDAC cancer cachexia. We established a correlation between elevated activin A and remodeling of visceral adipose tissue. Atrophy and fibrosis of visceral adipose tissue was examined in omental adipose tissue of Stage IV PDAC patients and gonadal adipose tissue of an orthotopic mouse model of PDAC. Remarkably, white visceral adipose tissue from both PDAC patients and mice exhibited decreased adipocyte diameter and increased fibrotic deposition. Strikingly, expression of thermogenic marker UCP1 in visceral adipose tissues of PDAC patients and mice remained unchanged. Thus, we propose that activin A signaling could be relevant to the acceleration of visceral adipose tissue wasting in PDAC-associated cachexia.",
author = "Xu, {Pauline C.} and Mikyoung You and Yu, {Seok Yeong} and Yi Luan and Maya Eldani and Caffrey, {Thomas C.} and Grandgenett, {Paul M.} and O{\textquoteright}Connell, {Kelly A.} and Shukla, {Surendra K.} and Chandramohan Kattamuri and Hollingsworth, {Michael A.} and Singh, {Pankaj K.} and Thompson, {Thomas B.} and Soonkyu Chung and Kim, {So Youn}",
note = "Funding Information: This work was supported by startup funds from UNMC (S.Y.K.); University of Nebraska Collaboration Initiative NRI2132270010 (S.Y.K. and S.C.); R01CA210439 (P.K.S.); and P50CA127297, U01CA210240, P30CA36727, and 5R50CA211462 for the UNMC Tissue Bank RAP Program. The results in Fig. 1A are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. The authors would like to thank Dr. Michel M. Ouellette for granting use of hTERT-HPNE cells, Dr. Dandan Zheng for providing images of CT scans, and Fang Qiu for providing biostatistician expertise. The authors would also like to give special thanks to Dr. Jean Grem, RAP Medical Oncologist; Dr. Dominick DiMaio, RAP Pathologist; Dr. Audrey Lazenby, RAP Pathologist; Dr. Yimin Sun from the Tissue Procurement and Storage Facility; and Salma Elhag and Dr. Benjamin Swanson from the Research Tissue Bank. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41598-022-05660-7",
language = "English (US)",
volume = "12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}