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Publication : NT-4-deficient mice lack sensitivity to meal-associated preabsorptive feedback from lipids.

First Author  Chi MM Year  2007
Journal  Am J Physiol Regul Integr Comp Physiol Volume  292
Issue  6 Pages  R2124-35
PubMed ID  17303678 Mgi Jnum  J:143021
Mgi Id  MGI:3822647 Doi  10.1152/ajpregu.00825.2006
Citation  Chi MM, et al. (2007) NT-4-deficient mice lack sensitivity to meal-associated preabsorptive feedback from lipids. Am J Physiol Regul Integr Comp Physiol 292(6):R2124-35
abstractText  Since mice with a deletion of the neurotrophin-4 (NT-4) gene exhibit a loss of both nodose ganglion neurons and vagal afferent terminals in the small intestines, we hypothesized that the reduced intestinal innervation of the NT-4 knockout (NT-4KO) mouse would lead to a corresponding reduction in the preabsorptive feedback from macronutrients. To explore this prediction, we measured meal patterns in NT-4KOs and controls, while, on different days, intragastric infusions of either lipids (Intralipid; 10%, 20%) or glucose (12.5%, 25%) were yoked to each animal's spontaneous feeding of a pelleted diet (approximately 1 kcal infused/1 kcal ingested). NT-4KO mice were relatively, though not completely, insensitive to the lipid infusions, whereas they were as sensitive as controls to glucose infusions. More specifically, the regulatory deficits of NT-4KOs included 1) attenuated satiation from the lipid infusions, as measured by smaller intrameal reductions of both meal size and meal duration, 2) defects in satiety associated with the fat infusions, as measured by smaller intermeal increases of both satiety ratio and intermeal interval, and (3) losses in daily compensatory responses for lipid calories. These results support the hypothesis that NT-4KO mice have deficits in macronutrient feedback from the gastrointestinal tract, indicate that the defects are specific insofar as they do not include impairments in the feedback of glucose infusions on feeding, and suggest that early feedback about dietary lipids is important in the regulation of satiation, satiety, and longer-term compensation of daily caloric intake.
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