Reduced Sensitivity to Cholecystokinin in Male Rats Fed a High-Fat Diet Is Reversible

Abstract

Adult rats chronically fed a high-fat (HF) diet maintain reduced sensitivity to cholecystokinin (CCK). We hypothesized that, similar to adult rats, pups fed a HF diet would also exhibit reduced sensitivity to CCK. To test this, male pups fed low-fat (LF) and HF isoenergetic (16.2 kJ/g) diets were administered CCK intraperitoneally (0.125-1 microg/kg) 1 wk following dietary adaptation. After receiving 0.5 microg/kg CCK, pups fed the HF diet suppressed food intake less (8.9 +/- 5.0%) than pups fed the LF diet (28.9 +/- 4.7%; P < 0.05) relative to intakes after saline administration. We then assessed the development and extinction of changes in CCK sensitivity by switching the diets between the groups. The HF-fed group, when switched to the LF diet, regained sensitivity by wk 4 and suppressed food intake following administration of 0.25 microg/kg CCK (33.1 +/- 5.7%; P < 0.05). The LF-fed group, when switched to the HF diet, lost sensitivity by wk 2 and did not suppress food intake after administrations of CCK compared with saline. Finally, we examined if HF-fed rats have an increased sensitivity to corn oil during brief access tests using a multibottle gustometer. At oil concentrations of 25, 75, and 100%, rats fed the HF diet sampled more oil than LF-fed rats (P < 0.05). These findings demonstrate that male rat pups fed a HF diet exhibit reduced sensitivity to CCK, the development of this reduced sensitivity is quicker than its extinction, and rats consuming a HF diet have increased oral sensitivity to oils.

The modulatory role of high fat feeding on gastrointestinal signals in obesity

“…Indeed, there is an inverse correlation between detection of oleic acid and BMI, and hyposensitivity to oleic acid is associated with increased energy intake and BMI [69]. Furthermore, we and others have shown that rats maintained on HF diet exhibit increased avidity for concentrated oil solutions compared to LF fed controls during brief access lick tests [70][71][72]. Therefore, it is plausible that long-term exposure to HF diet leads to oral taste desensitization, possibly through decreases in lipid-activated Release of neurotransmitters via LCFA activation by taste receptor cells is mediated by CD36 and possibly GPR40 and GPR120 through yet unknown mechanisms.…”

“…These changes in responses to CCK are reversible. For example, in-vitro desensitization of CCK that occurs very rapidly is reversed within minutes [149], while loss or restoration of CCK-8 sensitivity in in-vivo take two and three weeks, respectively [72].…”

Obesity: considerations about etiology, metabolism, and the use of experimental models

“…It has been well described that adult rats chronically fed a high-fat diet maintain reduced sensitivity to CCK. Swartz et al50 demonstrated that male rat pups fed a high-fat diet exhibit reduced sensitivity to CCK; the development of this reduced sensitivity is quicker than its extinction when the high-fat diet was switched to a low-fat diet.…”

Loss of Vagal Sensitivity to Cholecystokinin in Rats Born with Intrauterine Growth Retardation and Consequence on Food Intake

“…We effectively found that CCK-1R immunoreactivity was significantly lower in nodose ganglia of LP rats compared to control rats probably contributing to the resistance to CCK. A reduced sensitivity to a satietogenic dose of CCK, leading to hyperphagia, has already been shown in obesity-prone rats receiving standard chow (39) as well as in high-fat diet fed rats (40). In diet-induced obese rats, neurochemical analysis of VAN supports a vagal resistance to CCK and leptin in this model in which hyperphagia occurred concomitantly with this resistance (29).…”