Effect of the slimming agent oleoyl-estrone in liposomes on the body weight of Zucker obese rats.
OBJECTIVE
To determine whether the mechanisms by which estrone acyl-esters carried by lipoproteins induce the loss of body fat can affect Zucker fa/fa rats, since they are hyperphagic and could not eliminate excess energy through thermogenesis, two aspects essential for the slimming effect of oleoyl-estrone in normal rats.


METHODS
The rats were infused for 28 d (osmotic minipumps) with oleoyl-estrone in liposomes (Merlin-2) at a dose of 3.5 mmol/day.kg.


METHODS
Lean (L) and obese (O) Zucker rats.


METHODS
Body weight changes. Oxygen consumption, body composition (water, lipid, protein), nitrogen balance, plasma chemistry.


RESULTS
Treatment resulted in loss of body weight: 12.0% (28 g) L, 9.4% (34 g) O, mainly due to fat: 37.5% (10.8 g) L, 11.7% (15.5 g) O and water, preventing further increases in body weight and fat storage. Untreated rats increased their body weight: 10.5% (24 g) L, 32.2% (101 g) O and lipid stores: 20.3% (5.9 g) L, 39.8% (49.0 g) O, making the differences more marked. On day 28, glucose levels were maintained in all groups; in L, triacylglycerols increased and total cholesterol decreased; O showed no changes in plasma composition. In all rats, food intake decreased with treatment, and heat production (oxygen consumption) was unchanged (L) or slightly decreased (O). Energy expenditure per unit of fat-free mass remained unchanged. Protein balance was maintained in all groups; slimming was achieved without loss of body protein.


CONCLUSIONS
Treatment of genetically obese rats with oleoyl-estrone in liposomes (Merlin-2) results in sustained loss of body weight-mainly lipid, sparing protein-for up to 28 d, essentially preventing further increase in body weight and accumulation of lipid and protein. This is achieved through lower food intake and relatively small changes (if any) in energy expenditure.
Balada
F
F
Centre d'Investigació, Laboratoris SALVAT, SA, Esplugues de Liobregat, Spain.
Sanchis
D
D
Grasa
M M
MM
Virgili
J
J
Estruch
J
J
Fernández-López
J A
JA
Remesar
X
X
Alemany
M
M
D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D004195:Disease Models, Animal; D004337:Drug Carriers; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D004952:Esters; D004970:Estrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015918:Infusion Pumps, Implantable; D008081:Liposomes; D009584:Nitrogen / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D009829:Oleic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D014508:Urea / Q000097:blood / Q000378:metabolism
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D004337:Drug Carriers; D004952:Esters; D008081:Liposomes; D009829:Oleic Acids; D014280:Triglycerides; D004970:Estrone; C108709:oleoyl-estrone; D014508:Urea; D002784:Cholesterol; D009584:Nitrogen