Langer, Henning Tim, Ramsamooj, Shakti, Dantas, Ezequiel, Murthy, Anirudh, Ahmed, Mujmmail, Ahmed, Tanvir, Hwang, Seo-Kyoung, Grover, Rahul, Pozovskiy, Rita, Liang, Roger J, Queiroz, Andre Lima, Brown, Justin C, White, Eileen P, Janowitz, Tobias, Goncalves, Marcus D (May 2024) Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer. Acta Physiologica. e14167. ISSN 1748-1708
Preview |
PDF
10.1111.apha.14167.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview |
Abstract
AIM: To investigate systemic regulators of the cancer-associated cachexia syndrome (CACS) in a pre-clinical model for lung cancer with the goal to identify therapeutic targets for tissue wasting. METHODS: Using the Kras/Lkb1 (KL) mouse model, we found that CACS is associated with white adipose tissue (WAT) dysfunction that directly affects skeletal muscle homeostasis. WAT transcriptomes showed evidence of reduced adipogenesis, and, in agreement, we found low levels of circulating adiponectin. To preserve adipogenesis and restore adiponectin levels, we treated mice with the PPAR-γ agonist, rosiglitazone. RESULTS: Rosiglitazone treatment increased serum adiponectin levels, delayed weight loss, and preserved skeletal muscle and adipose tissue mass, as compared to vehicle-treated mice. The preservation of muscle mass with rosiglitazone was associated with increases in AMPK and AKT activity. Similarly, activation of the adiponectin receptors in muscle cells increased AMPK activity, anabolic signaling, and protein synthesis. CONCLUSION: Our data suggest that PPAR-γ agonists may be a useful adjuvant therapy to preserve tissue mass in lung cancer.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > nutritional and metabolic diseases organism description > animal diseases & disorders > nutritional and metabolic diseases > cachexia diseases & disorders > cancer > cancer types > lung cancer organism description > animal > mammal organism description > animal > mammal > rodent > mouse organism description > animal > mammal > rodent diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL labs > Janowitz lab CSHL Cancer Center Program |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 23 May 2024 |
| Date Deposited: | 28 May 2024 14:42 |
| Last Modified: | 20 Nov 2024 16:11 |
| PMCID: | PMC11250533 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41568 |
Actions (login required)
 |
Administrator's edit/view item |