Leptin resistance does not induce hyperphagia in the rat

Abstract

Leptin has been thought to work as a mediator for body weight control by inhibiting food intake. Leptin, however, cannot prevent obesity induced by a high-fat diet (HFD) probably because of leptin resistance. We investigated daily feeding and weight gain when ordinary chow (OC) was changed to a HFD in male rats. Food intake, by weight, significantly increased the next day, but gradually decreased until at 20 days the HFD intake contained the same calories as consumed by the OC-fed control rats. The reduction in food intake occurred only during the night without change of preference for the HFD, even after leptin resistance had developed. Nonetheless, the HFD-fed rats gained more weight than the controls. From the present experiment, it is concluded that leptin resistance does not induce hyperphagia, and suggested that body weight is not regulated to be constant.

Fig. 1

Daily food intake (expressed by weight (a) or energy (b)) and body weight (c) of the male rats fed on ordinary chow (OC) or a high-fat diet (HFD). The food for half of the rats (n = 8) was changed from OC to the HFD on day −1; other rats (n = 8) were continued to be fed OC. Food intake increased temporally after the food change from OC to HFD, but gradually decreased to the amount which contained the same amount of calories and remained stable even after their body weight was significantly heavier than that of OC rats. Values are group mean ± SEM. *P < 0.05, **P < 001 between OC and HFD rats

Fig. 2

Mean food intake of OC rats (n = 8) and HFD rats (n = 8) during light and dark period between 100 and 110 days after the initiation of HFD feeding. Values are group mean ± SEM. **P < 001 between OC and HFD rats

Fig. 3

Response to leptin and to the change of food from OC to the HFD in the rats fed OC or HFD. After 104 days fed on the HFD, the anorexigenic effect of leptin was tested by injecting 20 μg of leptin or 5 μl of saline into a lateral cerebral ventricle of in the OC (n = 8, respectively) and the HFD (n = 8, respectively) rats (a food intake, b body weight change). The HFD rats were tested again after their food was returned to the OC for 10 days (HFD + OC group). Only OC rats showed leptin sensitivity and HFD rats and HDF + OC rats were insensitive to leptin. Values are mean ± SEM. *P < 0.05, between leptin and saline injection. Changes in food intake after food was switched from ordinary chow (OC) to the high-fat diet (HFD) in leptin-resistant and leptin-responsive rats (c). Rats were made leptin-resistant by HFD feeding for 104 days; these rats were then fed OC for 10 days, then HFD was returned on day −1 (n = 8). The leptin-resistant and leptin-sensitive rats showed similar patterns of food intake responses to the HFD. Values are mean ± SEM. *P < 0.05, between −1 and 1 day values in both leptin-resistant and leptin-sensitive rats

Fig. 4

A change of preference for the HFD. A food preference test was performed using 7 male rats. They were presented with both CO and the HFD. HDF preference was expressed as percentage of the HFD of total daily food intake. The rats constantly preferred the HFD to OC throughout the experimental period