Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer.
Acta Physiol (Oxf)
; 240(8): e14167, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38779820
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cachexia
/
Adiponectin
/
Rosiglitazone
/
Lung Neoplasms
Limits:
Animals
Language:
En
Journal:
Acta Physiol (Oxf)
Journal subject:
FISIOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
United States