Sensitivity of ob/ob mice to leptin-induced adipose tissue apoptosis.

OBJECTIVE: ob/ob mice have increased sensitivity to many of leptin's effects. The primary objective of this experiment was to determine whether ob/ob mice demonstrated increased sensitivity to leptin-induced adipose tissue apoptosis.

RESEARCH METHODS AND PROCEDURES: Fifteen-week-old female ob/ob and Ob/? mice received 0 (saline), 2.5, or 10 microg/d leptin for 14 days through subcutaneous (sc) osmotic minipumps. Food intake (FI), body temperature, physical activity, and body weight were measured daily. Body composition and weights and adipose tissue apoptosis (percentage DNA fragmentation) of inguinal, parametrial, and retroperitoneal fat pads were determined at the end of the study.

RESULTS: FI decreases were more pronounced in ob/ob. Leptin (10 microg/d) decreased total FI 71% in ob/ob and 34% in Ob/? (p < 0.05). Body weight was decreased by both doses of leptin in ob/ob (p < 0.01) but was unchanged in Ob/?. Leptin increased body temperature in ob/ob but not in Ob/?. Physical activity was increased 400% by 10 microg/d leptin in ob/ob (p < 0.01) but decreased 13% in Ob/? (p < 0.01). Body fat content of ob/ob was reduced by both leptin doses, whereas only 10 microg/d leptin decreased body fat in Ob/?. Fat pad weights were decreased similarly by leptin in both genotypes. However, apoptosis was increased by leptin in all three fat pads in ob/ob, whereas Ob/? showed significant increases only in retroperitoneal.

DISCUSSION: ob/ob mice had greater overall sensitivity to leptin. Although ob/ob mice appeared to be more sensitive than Ob/? mice to leptin-induced adipose tissue apoptosis, there were differences among adipose depots in responsiveness to leptin-induced apoptosis.