Adaptation to a high-fat diet leads to hyperphagia and diminished sensitivity to cholecystokinin in rats.

Rats fed high-fat (HF) diets exhibit reduced sensitivity to some peptide satiety signals. We hypothesized that reduced sensitivity to satiety signals might contribute to overconsumption of a high-energy food after adaptation to HF diets. To test this, we measured daily, 3-h intake of a high-energy, high-fat (HHF, 22.3 kJ/g) test food in rats fed either low-fat (LF) or HF, isoenergetic (16.2 kJ/g) diets. During testing, half of each group received the HHF test food (LF/HHF; HF/HHF), whereas the other half received their respective maintenance diet (LF/LF; HF/HF). Rats fed a HF diet ate more of the HHF food during the 3-h testing period than LF-fed rats (HF/HHF = 7.7 +/- 0.3 g vs. LF/HHF = 5.5 +/- 0.2 g; P = 0.003). Rats tested on their own maintenance diets had similar intakes (HF/HF = 3.2 +/- 0.2 g vs. LF/LF = 3.7 +/- 0.3 g), which were lower (P < or = 0.008) than intakes of rats tested on HHF. HHF-tested rats did not differ in body weight by the end of wk 2 of testing. In a subsequent short-term choice preference test, rats exhibited an equal relative preference for HHF irrespective of their maintenance diets (HF = 63.1%, LF = 68.1%, P = 0.29). Finally, we examined the effect of intraperitoneal NaCl or cholecystokinin (CCK)-8 (100 and 250 ng/kg) injection on 1-h food intake. Both doses of CCK significantly suppressed food intake in LF-fed rats but not HF-fed rats. These results demonstrate that chronic ingestion of a HF diet leads to short-term overconsumption of a high-energy, high-fat food compared with LF-fed cohorts, which is associated with a decreased sensitivity to CCK.