Feeding and temperature responses to intravenous leptin infusion are differential predictors of obesity in rats

Obesity is frequently associated with leptin resistance. The present study investigated whether leptin resistance in rats is present before obesity develops, and thus could underlie obesity induced by 16 wk exposure to a liquid, palatable, high-energy diet (HED). Before HED exposure, male Wistar rats ( weighing between 330 and 360 g) received intravenous infusions of 20 mug leptin 2 h before dark (similar to57 mug/kg rat). Relative to saline infusion, this caused a highly variable effect on food intake ( ranging between -94 and + 129%), with food intake suppression that appeared negatively correlated with HED-induced increases in body weight gain, caloric intake, adiposity, and plasma leptin levels. In contrast, leptin's thermogenic response was positively correlated to body weight gain linked to weights of viscera, but not to adiposity. Before HED exposure, leptin unexpectedly increased food intake in some rats (fi +, n = 8), whereas others displayed the normal reduction in food intake ( fi +, n = 7). HED-exposed fi + rats had higher plasma leptin levels, retroperitoneal fat pad weight, HED intake, and body weight gain than fi - and chow-fed rats. These parameters were also higher in HED-exposed fi - rats relative to chow rats, except for plasma leptin concentrations. It is concluded that leptin's reduced efficacy to suppress food intake could predict obesity on an HED. An unexpected orexigenic effect of leptin might potentially contribute to this as well.