Self -paced infusions of lipids and carbohydrates in the NT-4 deficient mouse: Role of vagal afferents in providing feedback from gastrointestinal tract
Abstract
Previous studies have shown that mice with a deletion of the neurotrophin-4 (NT-4) gene exhibit a loss of vagal sensory neurons (∼50%) and afferent innervation to the gastrointestinal (GI) tract. Because of the importance of the vagus nerve in providing nutrient feedback from the GI tract to the brain, we hypothesized that the reduced intestinal innervation of the NT-4 knock out (NT-4KO) mouse would lead to a corresponding reduction in the pre-absorptive feedback from infused macronutrients. To explore the hypothesis, we first developed, using the C57BL/6 control strain, a new paradigm; this protocol involved delivering small (37 μl), discrete intragastric infusions of macronutrients yoked to self-paced ingestion of 20-mg pellets of a maintenance diet (Experiment 1). With the protocol standardized, we then compared the responses of S129 controls and NT-4KO mice to Intralipid (10%, 20%; Experiment 2) and glucose (12.5%, 25%; Experiment 3) with meal pattern analysis over 20-hr daily trials for each infusion condition. NT-4KO mice were relatively, though not completely, insensitive to the infusions of lipids, whereas they were as sensitive as controls to glucose infusions. More specifically, the regulatory deficits of the NT-4KOs included attenuated satiation from the lipid infusions, as measured by intra-meal reductions of both meal size and meal duration, defects in satiety associated with the fat infusions, as measured by reductions in inter-meal effects of lipids on both satiety ratios and intermeal intervals, and losses in daily compensatory responses for lipid calories, as measured by failures to reduce pellet consumption over 20-hr trials with IG infusions. These results (a) confirm the hypothesis that NT-4KO mice have deficits in macronutrient feedback from the GI tract, (b) indicate that the early feedback about dietary lipids is important in the regulation of satiation, satiety, and longer-term compensation for daily caloric overshoot, and (c) indicate that the defects are specific insofar as they do not include impairments in the feedback of glucose infusions on feeding.
Degree
Ph.D.
Advisors
Powley, Purdue University.
Subject Area
Neurology|Physiological psychology
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