Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer

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

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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:	Janowitz, Tobias
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:	28 May 2024 14:42
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41568

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