Therapeutic potential of AAV-FL-Klotho in obesity: Impact on weight loss and lipid metabolism in mice.
Biochim Biophys Acta Mol Basis Dis
; 1870(3): 167055, 2024 03.
Article
in En
| MEDLINE
| ID: mdl-38325589
ABSTRACT
Klotho, an anti-aging protein, has gained attention for its protective effects against various diseases, including metabolic disorders, through recombinant Klotho administration. However, the potential of Klotho as a target for gene therapy requires further exploration, as it remains relatively understudied in the context of metabolic disorders. In this study, we demonstrate that AAV-full length(FL)-Klotho administration induces weight loss in mice and provides protection against high-fat diet (HFD)-induced obesity and hepatic steatosis, concurrently reducing the weights of white adipose tissue and liver. AAV-FL-Klotho administration also enhanced thermogenic gene expression in brown adipose tissue (BAT) and improved the morphology of interscapular BAT. The weight loss effect of AAV-FL-Klotho was found to be, at least in part, mediated by UCP1-dependent thermogenesis in brown adipocytes, potentially influenced by hepatokines secreted from AAV-FL-Klotho-transduced hepatocytes. These findings suggest that AAV-FL-Klotho is an attractive candidate for gene therapy to combat obesity. Nevertheless, unbiased experiments have also revealed disturbances in lipid metabolism due to AAV-FL-Klotho, as evidenced by the emergence of lipomas and increased expression of hepatic lipogenic proteins.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lipid Metabolism
/
Metabolic Diseases
Limits:
Animals
Language:
En
Journal:
Biochim Biophys Acta Mol Basis Dis
Year:
2024
Document type:
Article
Country of publication:
Netherlands