Out-licensing

Elucidation of Liver-Secreted Factor of 4 Kda (Lsf4): Implicated in Cholesterol and Obesity Related Diseases

Using microarray gene expression analysis and validation by real-time quantitative PCR, the expression of a mRNA encoding a putative 76 amino acid, secreted protein was found to negatively correlate with fasting triglyceride and cholesterol levels. It was also confirmed that the mRNA encodes a secreted protein. Based on the primary site of expression being the liver, the gene encoding the protein was named "Liver-Secreted Factor of 4 kDa" (Lsf4). A recombinant adenovirus was used to increase the expression Lsfa4 mRNA in two mouse models of obesity, KK-A (y) and Lepob/Lepob mice. Over-expression of LSF4 by adenovirus injection significantly, and reproducibly, reduced fasting triglyceride and cholesterol levels in both models. Additionally, the expression of a key gene involved in lipogenesis (fatty acid synthase) and FAS protein levels were reduced by LSF4 adenoviral treatment in Lepob/Lepob mice.

Conclusion

Full-length LSF4 peptide derivatives, homologues, analogues, or mimetics thereof, delivered by oral intake, injection, subcutaneous patch, or intranasal routes, could be used as therapeutic or diagnostic agents for hypercholesterolemia, hypertriglyceridaemia, insulin resistance, obesity, diabetes, and/or energy imbalance.

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Preclinical