Background

Intermittent (INT) access to high-fat diet (HFD) can induce excessive intake phenotypes in rodents. During INT HFD, rats consume more kcal than chow-maintained controls, largely due to increased meal size. We hypothesized that impaired satiation contributes to this effect.

Methods

Female rats with intragastric (IG) catheters (n=6-9/group) received either chow, INT (20 h every 7th day at dark onset) or continuous (CONT) access to 45% HFD in addition to chow. First, we examined satiation responses by giving rats IG infusions (3.3 ml; 1 ml/min) of saline or Ensure Plus (5 kcal) 15 min before dark, and food intake was measured continuously. In a second study, we tested the satiating effect of amylin treatment (5 or 10 ug/kg) using a similar design (n=13-18/group; INT HFD 20 h every 4th day). We then tested amylin responses after rats (n=7/group) were returned to chow-only for five weeks.

Results

IG Ensure reduced intake relative to saline in chow rats from 30 m (61%) to 10 h (13-21%)(P’s<0.05). In CONT rats, Ensure reduced 30 m intake by 54% (P<0.05). INT rats were tested on chow and INT HFD days. On each, the effect of Ensure emerged at 1 h and was of smaller magnitude (chow day: 14%; HFD day: 25%). Meal pattern analysis showed that the major effect of Ensure was on meal size, but this was not present in INT rats, suggesting a reduction in nutrient-induced satiation. Amylin treatment in chow rats lowered intake relative to vehicle from 30 m (47%) to 4 h (15%), and 10 ug/kg amylin reduced first meal size (32%)(P’s<0.05). CONT rats showed a less robust response, only significantly lowering intake after 10 ug/kg amylin (13-18%). On chow days, INT rats also failed to respond to 5 ug/kg amylin and during INT HFD access, amylin had no effect. Five weeks without HFD did not fully restore amylin responses in INT and CONT rats.

Conclusions

We conclude that impaired satiation responses, mediated in part by reduced sensitivity to amylin, may explain the elevated intake observed upon INT HFD access.