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

Abstract

AbstractAimTo 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.MethodsUsing 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.ResultsRosiglitazone 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.ConclusionOur data suggest that PPAR‐γ agonists may be a useful adjuvant therapy to preserve tissue mass in lung cancer.