A gastrointestinal lipase inhibitor reduces progression of atherosclerosis in mice fed a western-type diet.
To investigate whether gastrointestinal lipase inhibition reduces the progression of a western-type diet induced atherosclerosis, male apolipoprotein-E knockout (apoE KO) mice were administered orlistat ((S)-1-[[(S, 2S, 3S)-3-hexyl-4-oxo-2-oxetanyl] methyl]dodecyl-(S)-2-formamido-4-methylvalerate) mixed with a western-type diet for 8 weeks. Orlistat significantly reduced plasma triglyceride levels, but not total cholesterol levels, at 4 and 8 weeks of treatment. Increase in plasma triglyceride levels after oral olive oil loading in the mice fed a western-type diet was significantly suppressed in the orlistat treated group at 4 weeks of treatment. After 8 weeks treatment, atherosclerotic lesion area in the aorta of the orlistat treated group was significantly smaller than that of the control group. These results suggest that gastrointestinal lipase inhibition reduces the progression of atherosclerosis through a triglyceride-lowering effect, via inhibition of fat absorption.
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Kashima 2-1-6, Yodogawa-ku, Osaka 532-8514, Japan. koji_ueshima@po.fujisawa.co.jp
Koji
K
Ueshima
Hitomi
H
Akihisa-Umeno
Akira
A
Nagayoshi
Shoji
S
Takakura
Masahiko
M
Matsuo
Seitaro
S
Mutoh
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D002791:Cholesterol, Dietary / Q000009:adverse effects* / Q000494:pharmacology; D004036:Diet, Atherogenic; D041981:Gastrointestinal Tract / Q000201:enzymology*; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000077403:Orlistat; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D007783:Lactones; D014280:Triglycerides; D000077403:Orlistat; D008049:Lipase