Diet-derived nutrients mediate the inhibition of hypothalamic NPY neurons in the arcuate nucleus of mice during refeeding.
Fasting activates orexigenic neuropeptide Y neurons in the hypothalamic arcuate nucleus (ARC) of mice, which is reversed by 2 h refeeding with standard chow. Here, we investigated the contribution of diet-derived macronutrients and anorectic hormones to the reversal of the fasting-induced ARC activation during 2 h refeeding. Refeeding of 12-h-fasted mice with a cellulose-based, noncaloric mash induced only a small reduction in c-Fos expression. Refeeding with diets, containing carbohydrates, protein, or fat alone reversed it similar to chow; however, this effect depended on the amount of intake. The fasting-induced ARC activation was unchanged by subcutaneously injected amylin, CCK (both 20 microg/kg), insulin (0.2 U/kg and 0.05 U/kg) or leptin (2.6 mg/kg). Insulin and leptin had no effect on c-Fos expression in neuropeptide Y or proopiomelanocortin-containing ARC neurons. Interestingly, CCK but not amylin reduced the ghrelin-induced c-Fos expression in the ARC in ad libitum-fed mice, suggesting that CCK may inhibit orexigenic ARC neurons when acting together with other feeding-related signals. We conclude that all three macronutrients and also non-nutritive, ingestion-dependent signals contribute to an inhibition of orexigenic ARC neurons after refeeding. Similar to the previously demonstrated inhibitory in vivo action of peptide YY, CCK may be a postprandial mediator of ARC inhibition.
Becskei
Csilla
C
Institute of Veterinary Physiology and Zurich Centre of Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Lutz
Thomas A
TA
Riediger
Thomas
T
D000682:Amyloid / Q000008:administration & dosage; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism*; D002766:Cholecystokinin / Q000008:administration & dosage; D004032:Diet; D004040:Dietary Carbohydrates / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D004044:Dietary Proteins / Q000378:metabolism; D004435:Eating; D002149:Energy Intake; D005215:Fasting / Q000378:metabolism*; D005247:Feeding Behavior; D054439:Ghrelin / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage; D058228:Islet Amyloid Polypeptide; D020738:Leptin / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D000682:Amyloid; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D054439:Ghrelin; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D020738:Leptin; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin; D002766:Cholecystokinin