Please use this identifier to cite or link to this item: https://doi.org/10.1242/dmm.038240
Title: Leptin induces muscle wasting in a zebrafish kras-driven hepatocellular carcinoma (HCC) model
Authors: Yang, Q. 
Yan, C. 
Wang, X.
Gong, Z. 
Keywords: Kras protein, zebrafish
leptin
leptin receptor
protein p21
zebrafish protein
animal
carcinogenesis
disease model
fatty liver
feeding behavior
gene knockout
genetics
human
liver cell carcinoma
liver tumor
male
metabolism
muscle atrophy
mutation
pathology
signal transduction
upregulation
zebra fish
Animals
Carcinogenesis
Carcinoma, Hepatocellular
Disease Models, Animal
Fatty Liver
Feeding Behavior
Gene Knockout Techniques
Humans
Leptin
Liver Neoplasms
Male
Muscular Atrophy
Mutation
Proto-Oncogene Proteins p21(ras)
Receptors, Leptin
Signal Transduction
Up-Regulation
Zebrafish
Zebrafish Proteins
Issue Date: 2019
Publisher: NLM (Medline)
Citation: Yang, Q., Yan, C., Wang, X., Gong, Z. (2019). Leptin induces muscle wasting in a zebrafish kras-driven hepatocellular carcinoma (HCC) model. Disease models & mechanisms 12 (2). ScholarBank@NUS Repository. https://doi.org/10.1242/dmm.038240
Abstract: Cancer cachexia affects up to 80% of patients with advanced solid cancer and leads to excessive muscle wasting. Here, using an inducible zebrafish hepatocellular carcinoma (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 that leptin expression progressively increased 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 wild-type background. Chemical inhibitors targeting leptin signaling also alleviated the muscle-wasting phenotype, indicating that leptin signaling may be a new therapeutic target for cancer patients with muscle wasting. © 2019. Published by The Company of Biologists Ltd.
Source Title: Disease models & mechanisms
URI: https://scholarbank.nus.edu.sg/handle/10635/174509
ISSN: 17548411
DOI: 10.1242/dmm.038240
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