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

Langer, Henning Tim, Ramsamooj, Shakti, Dantas, Ezequiel, Murthy, Anirudh, Ahmed, Mujmmail, Hwang, Seo-Kyoung, Grover, Rahul, Pozovskiy, Rita, Liang, Roger J, Queiroz, Andre Lima, Brown, Justin C, White, Eileen P, Janowitz, Tobias, Goncalves, And Marcus D (August 2023) Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer. bioRxiv. (Submitted)

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Abstract

The cancer associated cachexia syndrome (CACS) is a systemic metabolic disorder resulting in loss of body weight due to skeletal muscle and adipose tissues atrophy. CACS is particularly prominent in lung cancer patients, where it contributes to poor quality of life and excess mortality. 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. 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. 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 diseases & disorders > nutritional and metabolic diseases > cachexia
CSHL Authors:	Janowitz, Tobias
Communities:	CSHL labs > Janowitz lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2 August 2023
Date Deposited:	02 Nov 2023 12:44
Last Modified:	02 Nov 2023 12:44
PMCID:	PMC10418114
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41299

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