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Published on: November 24, 2020
Reduced sensitivity to cholecystokinin in male rats fed a high-fat diet is reversible
Timothy D Swartz1, David M Savastano, Mihai Covasa
1Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA 16802, USA.
Insights
Male rat pups fed a high-fat (HF) diet show reduced sensitivity to cholecystokinin (CCK), impacting food intake regulation. This reduced sensitivity develops quickly and is linked to increased oral fat preference.
Area of Science:
- Physiology
- Nutrition
- Endocrinology
Background:
- Adult rats on high-fat (HF) diets exhibit reduced cholecystokinin (CCK) sensitivity.
- CCK plays a crucial role in satiety and food intake regulation.
Purpose of the Study:
- To investigate if male rat pups fed a HF diet also display reduced CCK sensitivity.
- To examine the development and extinction of CCK sensitivity changes.
- To assess oral fat sensitivity in HF-fed rats.
Main Methods:
- Male rat pups were fed isoenergetic low-fat (LF) or HF diets.
- CCK was administered intraperitoneally to assess food intake suppression.
- Dietary interventions were switched to evaluate sensitivity changes.
- Brief access tests with corn oil were conducted using a gustometer.
Main Results:
- HF-fed pups showed significantly less food intake suppression after CCK administration compared to LF-fed pups.
- Rats switched from HF to LF diet regained CCK sensitivity within 4 weeks.
- Rats switched from LF to HF diet lost CCK sensitivity within 2 weeks.
- HF-fed rats exhibited increased oral sampling of corn oil at various concentrations.
Conclusions:
- Male rat pups fed a HF diet develop reduced CCK sensitivity.
- The development of reduced CCK sensitivity is faster than its extinction.
- HF diet consumption increases oral sensitivity to fats in rats.
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.

