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