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In order to assess the long-term impact of a complete depletion of glucocorticoids on plasma leptin levels, we bilaterally adrenalectomized 20 lean rats, and analysed glucocorticoids and leptin levels for 20 consecutive days. Results demonstrate that the adrenalectomy (ADX) significantly lowered the leptin levels, as compared to sham-operated controls. On the other hand, a significant increase in leptin levels was noticeable from day 1 to day 20 of the experiment in the sham-operated controls, even though corticosterone levels remained stable during that same period. Plasma leptin concentration was proportional to body fat content. These results would indicate a non-causal relationship between glucocorticoids and leptin levels in the context of a lipostat in the lean rat., (Copyright 2000 Academic Press.)

The genes encoding the mature forms of mouse (mOB) and human OB (hOB) protein (also called leptin) were fused to the secretion signal coding sequence of the Escherichia coli outer membrane protein A (sOMP A). The hybrid genes were preceded by a ribosome binding site (RBS) and were expressed under transcriptional control of both the lipoprotein promoter (Plpp) and the lac promoter-operator (POlac). The recombinant fusion proteins were efficiently expressed and exported into the periplasmic compartment of E. coli cells from where they were recovered by osmotic shock as soluble mature polypeptides with the sOMP A precisely removed. Recombinant mOB and hOB proteins were also produced in Sf9 insect cells using the baculovirus expression system. Milligram quantities of both proteins were purified to homogeneity using ion-exchange, hydrophobic interaction chromatography and gel filtration and were found to be biologically active and to have antiobesity effects upon testing in genetically obese ob/ob mice.

The six major research advances in metabolic and hormonal controls of food intake that have altered the direction or have broadened the scope of the field in the last 25 years are discussed. The advances selected are: (1) GI processes and meal termination-the CCK pathway; (2) Brain insulin hypothesis; (3) Glucose-dependent processes in periphery, plasma, and brain including the transient declines in blood glucose signaling meal initiation; (4) Fatty acid oxidation in the liver; (5) Behavioral and metabolic patterns; and (6) New pathways from molecular genetics and molecular biology-the OB protein pathway., (Copyright 1997 Academic Press Limited.)