PUBLICATION
Leptin induces muscle wasting in kras-driven hepatocellular carcinoma (HCC) model in zebrafish
- Authors
- Yang, Q., Yan, C., Wang, X., Gong, Z.
- ID
- ZDB-PUB-190206-5
- Date
- 2019
- Source
- Disease models & mechanisms 12(2): (Journal)
- Registered Authors
- Gong, Zhiyuan, Wang, Xu
- Keywords
- Cancer cachexia, Leptin, Leptin receptor (Lepr), Liver cancer, Muscle wasting, Zebrafish
- MeSH Terms
-
- Animals
- Carcinogenesis/pathology
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/pathology*
- Disease Models, Animal
- Fatty Liver/pathology
- Feeding Behavior
- Gene Knockout Techniques
- Humans
- Leptin/metabolism*
- Liver Neoplasms/genetics
- Liver Neoplasms/pathology*
- Male
- Muscular Atrophy/pathology*
- Mutation/genetics
- Proto-Oncogene Proteins p21(ras)/metabolism*
- Receptors, Leptin/metabolism
- Signal Transduction
- Up-Regulation
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- PubMed
- 30718259 Full text @ Dis. Model. Mech.
Citation
Yang, Q., Yan, C., Wang, X., Gong, Z. (2019) Leptin induces muscle wasting in kras-driven hepatocellular carcinoma (HCC) model in zebrafish. Disease models & mechanisms. 12(2):.
Abstract
Cancer cachexia affects up to 80% of the patients with advanced solid cancer and leads to excessive muscle wasting. Here, using an inducible zebrafish HCC model driven by oncogenic krasG12V , we observed a progressive muscle wasting phenotype in adult zebrafish, characterized by significant loss of body weight and muscle fibers. By differential feeding, we observed that overfeeding caused fatty liver, accelerated carcinogenesis and muscle wasting. Interestingly, leptin, an obesity hormone, was upregulated in oncogenic hepatocytes and overfeeding groups. We also found a progressively increased leptin expression during human liver disease progression. By using leptin receptor (lepr) knockout fish, we found that tumor fish in the lepr mutant background had a higher survival rate and significantly lower muscle wasting level after tumor induction than the tumor fish in the wildtype background. Chemical inhibitors targeting leptin signaling also alleviated muscle wasting phenotype, indicating that the leptin signaling may be a new therapeutic target for cancer patients with muscle wasting.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping