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Abstract
The aim of this study was to investigate the effect of long-term nutrient intake on
the central response to the anorexigenic gut hormone CCK. C57BL/6 mice were fed one
of three diets for 6 weeks: standard high carbohydrate (HC), high fat (HF), or high
protein (HP). Assessment of brain response to cholecystokinin (CCK) by manganese-enhanced
MRI (MEMRI) showed a reduction in neuronal activity both in an appetite-related area
(ventromedial nucleus of the hypothalamus) and areas associated with reward (nucleus
accumbens and striatum) regardless of diet. When comparing diet effects, while the
HF diet did not induce any change in activity, reductions in MEMRI-associated signal
were found in the paraventricular nucleus (PVN) and lateral hypothalamic area (LHA)
when comparing the HP to the HC diet. In addition, a significant interaction was found
between CCK administration and the HF diet, shown by an increased activation in the
PVN, which suggests a decrease the inhibiting action of CCK. Our results put forward
that the long-term intake of an HP diet leads to a reduction in basal hypothalamic
activation while a high-fat diet leads to desensitization to CCK-induced effects in
the hypothalamus.