Exaggerated response to mild stress in rats fed high-fat diet.

It has been suggested that high-fat (HF) diet exaggerates the stress-induced release of glucocorticoids due to activation of the hypothalamic-pituitary-adrenal (HPA) axis. In an initial experiment, in which rats were fed HF diet for 4 days, we found that HF-fed controls stopped gaining weight, indicating that they were hyperresponsive to the mild stress of tail bleeding but responded the same as low-fat (LF)-fed rats to the more severe stress of restraint. A second experiment confirmed these results when rats fed a HF diet for 4 days showed an exaggerated corticosterone release in response to an intraperitoneal injection of saline and movement to a novel cage, compared with LF-fed rats. Experiment 3 tested the same parameters as experiment 2 but interchanged the diets. This allowed us to differentiate between the effects of the dietary fat and the novelty of the diet. Additionally, this experiment determined whether hyperresponsiveness to mild stress in HF-fed rats was sustained during a prolonged exposure to diet. The results confirmed that a HF diet, not novelty, exaggerated the endocrine stress response after 9 days on the diet but that the effect was no longer present after 23 days on the diet. The hyperresponsiveness of the HPA axis in HF-fed rats is similar to that observed in animals that have been exposed to a significant chronic or acute stress, suggesting that the HF diet may initially be perceived as a stressor.