High-fat hyperphagia in neurotrophin-4 deficient mice reveals potential role of vagal intestinal sensory innervation in long-term controls of food intake.
Neurotrophin-4 (NT-4) deficient mice exhibit substantial loss of intestinal vagal afferent innervation and short-term deficits in feeding behavior, suggesting reduced satiation. However, they do not show long-term changes in feeding or body weight because of compensatory behaviors. The present study examined whether high-fat hyperphagia induction would overcome compensation and reveal long-term effects associated with the reduced vagal sensory innervation of NT-4 mutants. First, modifications of a feeding schedule previously developed in rats were examined in wild-type mice to identify the regimen most effective at producing hyperphagia. The most successful schedule, which was run for 26 days, included access to a 43%-fat diet and pelleted chow every other day and access to only powdered chow on the alternate days. On high-fat access days mice consumed 25% more calories than mice with continuous daily access to the same high-fat diet and pelleted chow. This feeding regimen also induced hyperphagia in NT-4 deficient mice and their wild-type controls: on high-fat exposure days mutants consumed 35% more calories relative to continuous-access mutants, and wild types ate 25% more than continuous-access wild types. Moreover, on high-fat access days the alternating NT-4 mutants significantly increased caloric intake by 9% compared to alternating wild types. Thus, high-fat hyperphagia appeared to override compensation, permitting short-term changes in meal consumption by mutants that accrued into long-term changes in total daily food intake. This raises the possibility that intestinal vagal sensory innervation contributes to long-term, as well as to short-term regulation of food intake.
Behavioral Neurogenetics Laboratory, Department of Psychological Sciences, 703 Third Street, Purdue University, West Lafayette, IN 47907, USA.
Mardi S
MS
Byerly
Edward A
EA
Fox
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001069:Appetite Regulation; D004041:Dietary Fats / Q000378:metabolism*; D004435:Eating; D005246:Feedback / Q000502:physiology; D006963:Hyperphagia / Q000503:physiopathology*; D007422:Intestines / Q000294:innervation* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000172:deficiency*; D014630:Vagus Nerve / Q000502:physiology*
D004041:Dietary Fats; D009414:Nerve Growth Factors; C073922:neurotrophin 4