Studies on the antiobesity activity of tetrahydrolipstatin, a potent and selective inhibitor of pancreatic lipase.
In summary, THL is a potent inhibitor of pancreatic lipase, which is both selective and irreversible in its action in vitro. It is also likely that THL inhibits pancreatic lipase in vivo, since its acute administration to mice and squirrel monkeys suppresses absorption of dietary triglycerides, without an apparent alteration in the absorption of fatty acids. The marked loss in body weight and carcass fat of DIO rats with subchronic administration of THL strongly suggests that inhibition of pancreatic lipase is a feasible strategy for the treatment of obesity. Whether obese humans will overeat in response to a reduction in body energy stores is not known. However, it is probable that compliance to a therapy which maintains the present level of food intake while inducing excretion of dietary fat, will be greater than a reducing diet alone or conjunction with the currently available antiobesity drugs.
Hoffmann-La Roche Inc., Nutley, NJ 07110.
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Hogan
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Fleury
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Hadvary
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Lengsfeld
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Meier
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Triscari
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Sullivan
D000818:Animals; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D007408:Intestinal Absorption / Q000187:drug effects; D007783:Lactones / Q000494:pharmacology*; D008049:Lipase / Q000037:antagonists & inhibitors*; D008253:Macaca mulatta; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D000077403:Orlistat; D010179:Pancreas / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D004041:Dietary Fats; D007783:Lactones; D000077403:Orlistat; D008049:Lipase