POSTNATAL-DEVELOPMENT OF THE OB GENE SYSTEM - ELEVATED LEPTIN LEVELS IN SUCKLING FA FA RATS/

The postnatal development of the ob gene system has been examined in Z ucker fa/fa and +/fa plus +/+ (referred to as +/?) rats. White adipose tissue was takes from animals aged 1 to 28 days. Before weaning, whit e fat was predominantly subcutaneous, the amount increasing rapidly af ter birth. ob mRNA was detected by Northern blotting in samples of ing uinal fat at 1 day of age and thereafter. Circulating leptin, measured by enzyme-linked immunosorbent assay, was also detectable from I day of age, the level rising to a peak by 10 days of age and then declinin g. The fa/fa genotype was determined from the size of the product afte r Msp I digestion of the Ob-receptor gene obtained by polymerase chain reaction amplification of genomic DNA. No statistically significant d ifference in ob mRNA level between fa/fa and +/? animals was obtained before 25 days of age. However, leptin levels were significantly highe r in the fa/fa mutant by 10 days of age, despite the absence of any si gnificant elevation in the weight of the major fat depots or in ob mRN A level. It is concluded that the ob gene is expressed and leptin prod uced early in postnatal life in rats; the elevation of circulating lep tin in suckling fa/fa animals indicates that dysregulation of the lept in system occurs before the overt development of the obese phenotype.