The pharmacological effect of
FR177391, isolated from Serratia liquefaciens No. 1821, was studied in normal animals and various types of animal models of
hypertriglyceridemia. Treatment of normal mice with
FR177391 resulted in an increase in
heparin-releasable
lipoprotein lipase (LPL) activity in the blood and epididymal fat tissue.
FR177391 treatment decreased
triglyceride (TG) and increased
high-density lipoprotein cholesterol in the blood in normal rats following 7 days treatment, suggesting potent LPL activating properties of
FR177391. Both Triton WR1339-induced severe and
fructose-induced mild
hypertriglyceridemia in rats were attenuated by
FR177391 treatment. Severely elevated levels of TG in db/db mice, an
insulin resistant diabetic animal model, also significantly decreased from 14 days of treatment with
FR177391.
FR177391 treatment for 9 days caused a decrease in the elevated levels of TG in mice induced by intraperitoneal inoculation of murine
lymphoma EL-4. Overall, this study demonstrated that
FR177391 can be possibly a LPL activating agent and that
FR177391 treatment improved
hypertriglyceridemia in various rat and mouse animal models. These results suggest that
FR177391 is a promising candidate compound for the management of
hypertriglyceridemia.