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. 1997 Sep 1;326(Pt 2):357–360. doi: 10.1042/bj3260357

Short-term treatment with oleoyl-oestrone in liposomes (Merlin-2) strongly reduces the expression of the ob gene in young rats.

D Sanchis 1, C Adán 1, A Ardévol 1, M Del Mar Grasa 1, C Cabot 1, F Balada 1, R Vilà 1, J Estruch 1, M Puerta 1, J A Fernández-López 1, X Remesar 1, M Alemany 1
PMCID: PMC1218678  PMID: 9291105

Abstract

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.

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