INSULIN INDUCES RAPID CHANGES OF PLASMA LEPTIN IN LEAN BUT NOT IN GENETICALLY-OBESE (FA FA) RATS/

OBJECTIVES: To evaluate the plasma leptin concentration in Bean and ge netically obese fa/fa rats and to assess the response to 2 h hyperinsu linaemia. BACKGROUND: The recently discovered peptide leptin is a puta tive link between the size of the adipose mass and the hypothalamic ce ntres controlling feeding behaviour. Several genetic models of animal obesity have been characterized as carriers of mutations of either the ob gene or leptin receptor. EXPERIMENTAL DESIGN: Lean (+/?) and obese (fa/fa) Zucker rats were studied under pentobarbital anaesthesia and underwent a 2 h euglycaemic hyperinsulinaemic clamp. Plasma leptin was measured in basal condition and at the end of the clamp study. Glucos e rate of disappearance was evaluated by means of the isotope dilution technique using 3-H-3-glucose as tracer. RESULTS: fa/fa rats showed a 40 fold higher leptin concentration compared to lean littermates (0.4 7 +/- 0.10 vs 19.55 +/- 1.50 ng/ml), P < 0.0001). Euglycaemic hyperins ulinaemia increased plasma leptin in lean but not in genetically obese rats. CONCLUSIONS: Our results suggest that insulin may be a regulato r of in vivo leptin secretion by adipose tissue of lean rats whereas i t is ineffective in increasing plasma leptin in obese Zucker rats.