Masoprocol decreases serum triglyceride concentrations in rats with fructose-induced hypertriglyceridemia.
Historically, extracts of the creosote bush have been used by native healers of the Southwest region of North America to treat symptoms of type 2 diabetes. More recently, we have shown that masoprocol (nordihydroguaiaretic acid), a pure compound isolated from the creosote bush (Larrea tridentata), decreases serum glucose and triglyceride (TG) levels when administered orally in rodent models of type 2 diabetes. The present studies were undertaken to determine if masoprocol also decreases TG concentrations in rats with fructose-induced hypertriglyceridemia (HTG), a nondiabetic model of HTG associated with insulin resistance and hyperinsulinemia. Serum TG levels, which were significantly higher after rats ate a fructose-enriched (60% by weight) diet for 14 days as compared with chow-fed controls (411 v 155 mg/dL, P < .01), decreased in a stepwise fashion in fructose-fed rats treated orally with masoprocol for 4 to 8 days over a dose range of 10 to 80 mg/kg twice daily. Using the nonionic detergent Triton WR 1339 to compare TG secretion rates in masoprocol- and vehicle-treated rats, masoprocol at a dose of 40 or 80 mg/kg twice daily, significantly reduced hepatic TG secretion (P < .01) and liver TG content (P < .001), whereas lower doses of masoprocol decreased serum TG without an apparent reduction in hepatic TG secretion. Administration of Intralipid (a fat emulsion) showed that the half-time for removal of TG from serum was also shorter in masoprocol-treated rats versus vehicle-treated controls (31 v 64 minutes, P < .05). In addition adipose tissue lipoprotein lipase (LPL) activity was increased in masoprocol-treated rats and adipose tissue hormone-sensitive lipase (HSL) activity was decreased. We conclude that masoprocol administration to rats with fructose-induced HTG results in lower serum TG levels associated with reduced hepatic TG secretion and increased peripheral TG clearance.
Scribner
K A
KA
Shaman Pharmaceuticals, South San Francisco, CA 94080-4812, USA.
Gadbois
T M
TM
Gowri
M
M
Azhar
S
S
Reaven
G M
GM
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005632:Fructose; D015228:Hypertriglyceridemia / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy; D007328:Insulin / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D005632:Fructose; D009637:Masoprocol; D008071:Lipoprotein Lipase