Leptin responses to glucose infusions in obesity-prone rats

The secretion of leptin is dually regulated. In fasting animals, plasma lep tin concentrations reflect body fat stores, whereas the incremental leptin response to fasting or refeeding most likely reflects insulin-mediated ener gy flux and metabolism within adipocytes. Impaired secretion of leptin in e ither pathway could result in obesity. We therefore measured plasma leptin concentrations in fasted animals and plasma leptin concentrations after an intravenous glucose infusion in a rat model of obesity. Young Sprague-Dawle y (S-D) and Fischer 344 (F344) rats had similar percent body fat and fastin g glucose and fasting leptin concentrations. However, F344 animals had high er insulin concentrations and leptin responses to intravenous glucose than did the S-D animals. The animals were then fed a control or high-fat diet f or 6 wk. High-fat fed animals gained more weight and body fat than did the control fed animals. Control and high-fat fed F344 animals gained similar t o 40% (P < 0.0001) more weight and > 100% (P < 0.01) more body fat than did the S-D animals. Fasting leptin concentrations and leptin concentrations a fter intravenous glucose infusions and feeding were more than double (P < 0 .05) in F344 animals compared with S-D animals. Whether an animal is fed a control or high-fat diet had little effect on the leptin response to intrav enous glucose. In conclusion, young, lean F344 animals, before the onset of obesity, demonstrated a greater acute leptin response to intravenous gluco se than similarly lean S-D animals. After a 6-wk diet, F344 animals had a g reater percent increase in body weight and insulin resistance and exhibited higher fasting leptin concentrations and a greater absolute leptin respons e to intravenous glucose compared with the S-D animals. The chronic diet (c ontrol or high fat) had little impact on the acute leptin response to intra venous glucose. F344 animals exhibit leptin resistance in young, lean anima ls and after aging and fat accumulation.