Fig. 5.

Effects of diet and leptin on body weight gain and hypothalamic PTP1B in leptin-deficient mice. Leptin-deficient ob/ob mice were placed on a LF or HF diet for 14 days (7–8 mice/group) and were also simultaneously implanted with sc osmotic minipumps delivering either saline or leptin (5 μg/day). On day 14, mice were killed, and levels of hypothalamic PTP1B mRNA were determined via real-time PCR. A: leptin infusion reduced body weight gain in both wild-type and ob/ob mice on a LF diet (*P < 0.01). However, the effect of leptin to reduce body weight gain was attenuated in mice on a HF diet. B: both leptin infusion and exposure to a HF diet increased hypothalamic PTP1B mRNA expression in LF-fed wild-type mice, consistent with the prior rat experiments. Additionally, these same effects were also replicated in ob/ob mice, indicating that HF diets are sufficient to increase PTP1B even in the absence of leptin (*P < 0.05 and †P < 0.10 compared with LF-saline).