Loss of body fat in lean parabiotic partners of ob/ob mice

The objective of this experiment was to confirm whether changes in serum leptin and leptin expression were consistent with it being the "lipostatic" factor implicated by earlier parabiosis studies. Lean (+/?) and obese (ob/ob) female C57B1/6J-ob mice were parabiosed (lean-ob/ob) at 7 wk of age. Controls were ob/ob-ob/ob and lean-lean pairs, and single lean and ob/ob mice. Pairs were maintained for 50 days. In ob/ob members of lean-ob/ob pairs serum insulin was normalized, food intake was suppressed, and body fat was reduced by 14%. Lean partners of ob/ob mice had a reduced rectal temperature and experienced a 37% reduction in body fat. Despite loss of fat, serum leptin and adipose leptin mRNA expression were unchanged in lean partners of ob/ob mice. These results suggest that, in lean-ob/ob parabiotic pairs, the ob/ob mouse responds to leptin originating in the lean parabiont, whereas the lean partner responds to a circulating signal, originating in the ob/ob mouse, that maintains leptin expression at inappropriate levels for the degree of adiposity of the lean animal.