Short-term treatment with oleoyl-oestrone in liposomes (Merlin-2) strongly reduces the expression of the ob gene in young rats.
Young female rats of 160-180 g were implanted with osmotic minipumps releasing 3.0 micromol/day per kg of oleoyl-oestrone in liposomes (Merlin-2) into the bloodstream for up to 14 days. Merlin-2 induced a loss of appetite in the first days, later recovered, and a decrease in body weight of 7%, which contrasts with the 15% increase in controls during the 2-week period. Neither plasma glucose nor urea was affected by treatment, but liver glycogen increased by 50% in 14 days. Insulin decreased slightly with Merlin-2 treatment. Plasma corticotropin (ACTH) and corticosterone showed a transient increase by day 6 of treatment. The expression of the ob gene in adipose tissue fell during the period studied to practically nil on day 14; circulating leptin levels decreased more than 70% from day 1 to day 14. Oestrone levels increased from 0.3 nM (controls) to a maintained 40-60 nM level for the rest of the experiment. Oleoyl-oestrone levels first increased 4-fold, to decrease again to the initial levels on day 10, increasing later to 100-fold on day 14. The three phases observed in food intake, weight loss and oleoyl-oestrone levels match fairly well, which supports the direct involvement of oleoyl-oestrone in body-weight control. However, the control of oleoyl-oestrone levels seems to be mediated in part by corticosterone. The practical disappearance of leptin synthesis coincides with the massive accumulation of oleoyl-oestrone in plasma. The results presented suggest the involvement of oleoyl-oestrone in the main mechanisms of control of body weight and its regulation by glucocorticoids and leptin.
Sanchis
D
D
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Spain.
Adán
C
C
Ardévol
A
A
Del Mar Grasa
M
M
Cabot
C
C
Balada
F
F
Vilà
R
R
Estruch
J
J
Puerta
M
M
Fernández-López
J A
JA
Remesar
X
X
Alemany
M
M
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004334:Drug Administration Schedule; D004337:Drug Carriers; D004952:Esters; D004970:Estrone / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000097:blood; D015918:Infusion Pumps, Implantable; D007328:Insulin / Q000097:blood; D020738:Leptin; D008081:Liposomes / Q000008:administration & dosage*; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics*; D019301:Oleic Acid / Q000008:administration & dosage* / Q000097:blood; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D015431:Weight Loss / Q000187:drug effects
D004337:Drug Carriers; D004952:Esters; D005938:Glucocorticoids; D007328:Insulin; D020738:Leptin; D008081:Liposomes; D011506:Proteins; D004970:Estrone; D019301:Oleic Acid