1. Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer.
- Author
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Langer HT, Ramsamooj S, Dantas E, Murthy A, Ahmed M, Ahmed T, Hwang SK, Grover R, Pozovskiy R, Liang RJ, Queiroz AL, Brown JC, White EP, Janowitz T, and Goncalves MD
- Subjects
- Animals, Mice, Muscle, Skeletal metabolism, Muscle, Skeletal drug effects, PPAR gamma metabolism, PPAR gamma agonists, Male, Adipose Tissue, White metabolism, Adipose Tissue, White drug effects, Mice, Inbred C57BL, Thiazolidinediones pharmacology, Thiazolidinediones therapeutic use, Rosiglitazone pharmacology, Rosiglitazone therapeutic use, Lung Neoplasms metabolism, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Cachexia metabolism, Cachexia drug therapy, Adiponectin metabolism
- 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., (© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)
- Published
- 2024
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