title: Peripherally injected cholecystokinin-induced neuronal activation is modified by dietary composition in mice.
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.
authors.affiliation: AgroParisTech, CNRH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, F-75005 Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Zeeni
authors.forename: N
authors.initials: N
authors.lastname: Nadkarni
authors.forename: J D
authors.initials: JD
authors.lastname: Bell
authors.forename: P C
authors.initials: PC
authors.lastname: Even
authors.forename: G
authors.initials: G
authors.lastname: Fromentin
authors.forename: D
authors.initials: D
authors.lastname: Tome
authors.forename: N
authors.initials: N
authors.lastname: Darcel
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D001931:Brain Mapping; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000494:pharmacology*; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017895:Manganese Compounds; D051379:Mice; D008810:Mice, Inbred C57BL; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation
chemical_list: D002756:Cholagogues and Choleretics; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D017895:Manganese Compounds; D002766:Cholecystokinin