Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition

Abstract

Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents.

Figure 1

SL pups gained more weight than NL pups, suggesting they experienced overnutrition, and had more fat as adults, despite no difference in their body weight. (A) Body weights of NL or SL mouse pups measured daily from P0 until weaning. SL mice began to diverge and weigh significantly more than NL mice beginning at P1 (open squares, NL; filled squares, SL). (B) Body weight during collection of meal pattern data shown at the start of the meal pattern analysis, body weight was not significantly different between NL and SL males, or between NL and SL females. (C) At 6–8 months of age, when fat pads were removed, body weights of both NL and SL males were higher than females. There was no difference within sex. (D) Total fat pad weights of SL males at 6–8 months of age, the age of the animals at nodose injection, were higher than NL males and females. Fat pad weights from SL females were not different from SL males, or either sex from NL. (E) Gonadal, and retroperitoneal fat pads from SL males weighed more than the respective fat pads from the other groups. * denotes p < 0.05.

Figure 2

At 3–4 months of age, SL mice displayed greater total daily intake than NL mice, and small trends in several meal parameters of SL mice appeared to account for this increase in daily food intake. (A) Total daily food intake by SL mice was slightly, but significantly higher than NL mice (open bars, NL; filled bars, SL). (B) SL mice showed a trend towards larger meal size than NL mice. (C) SL mice showed a trend towards longer meal durations than NL mice. (D) SL mice trended toward consuming more meals than NL mice. (E) SL mice showed a trend towards a decreased IMI as compared with NL mice. (F) Satiety ratio was significantly decreased in SL mice compared to NL mice. (G) Average food intake rate throughout the 18 hr of daily meal pattern collection was similar in mice raised in both SL and NL mice. (H) Average food intake rate during the first daily meal was higher in SL mice as compared with NL mice.

Figure 3

NL and SL mice showed similar average IGLE densities. IGLEs were labeled by anterograde WGA-HRP transport after injection into the left nodose ganglion followed by staining with TMB at 6–8 months of age.

Figure 4

Animals from both litter sizes qualitatively showed similar IGLE morphology. Examples are shown from an NL male (A), an SL male (B), an NL female (C), and an SL female (D). Arrows denote IGLEs. All IGLEs shown are from the 4–8 cm segment of the duodenum. All images are photomontages of equal magnification (total magnification, 100X). Scale bar is 200μm.