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Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling

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...

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Autores principales: Xu, Pauline C., You, Mikyoung, Yu, Seok-Yeong, Luan, Yi, Eldani, Maya, Caffrey, Thomas C., Grandgenett, Paul M., O’Connell, Kelly A., Shukla, Surendra K., Kattamuri, Chandramohan, Hollingsworth, Michael A., Singh, Pankaj K., Thompson, Thomas B., Chung, Soonkyu, Kim, So-Youn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803848/
https://www.ncbi.nlm.nih.gov/pubmed/35102236
http://dx.doi.org/10.1038/s41598-022-05660-7
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author Xu, Pauline C.
You, Mikyoung
Yu, Seok-Yeong
Luan, Yi
Eldani, Maya
Caffrey, Thomas C.
Grandgenett, Paul M.
O’Connell, Kelly A.
Shukla, Surendra K.
Kattamuri, Chandramohan
Hollingsworth, Michael A.
Singh, Pankaj K.
Thompson, Thomas B.
Chung, Soonkyu
Kim, So-Youn
author_facet Xu, Pauline C.
You, Mikyoung
Yu, Seok-Yeong
Luan, Yi
Eldani, Maya
Caffrey, Thomas C.
Grandgenett, Paul M.
O’Connell, Kelly A.
Shukla, Surendra K.
Kattamuri, Chandramohan
Hollingsworth, Michael A.
Singh, Pankaj K.
Thompson, Thomas B.
Chung, Soonkyu
Kim, So-Youn
author_sort Xu, Pauline C.
collection PubMed
description 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.
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spelling pubmed-88038482022-02-01 Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling Xu, Pauline C. You, Mikyoung Yu, Seok-Yeong Luan, Yi Eldani, Maya Caffrey, Thomas C. Grandgenett, Paul M. O’Connell, Kelly A. Shukla, Surendra K. Kattamuri, Chandramohan Hollingsworth, Michael A. Singh, Pankaj K. Thompson, Thomas B. Chung, Soonkyu Kim, So-Youn Sci Rep Article 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. Nature Publishing Group UK 2022-01-31 /pmc/articles/PMC8803848/ /pubmed/35102236 http://dx.doi.org/10.1038/s41598-022-05660-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xu, Pauline C.
You, Mikyoung
Yu, Seok-Yeong
Luan, Yi
Eldani, Maya
Caffrey, Thomas C.
Grandgenett, Paul M.
O’Connell, Kelly A.
Shukla, Surendra K.
Kattamuri, Chandramohan
Hollingsworth, Michael A.
Singh, Pankaj K.
Thompson, Thomas B.
Chung, Soonkyu
Kim, So-Youn
Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling
title Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling
title_full Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling
title_fullStr Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling
title_full_unstemmed Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling
title_short Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling
title_sort visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin a signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803848/
https://www.ncbi.nlm.nih.gov/pubmed/35102236
http://dx.doi.org/10.1038/s41598-022-05660-7
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