Effects of early postnatal overnutrition on meal pattern and vagal sensory innervation of the small intestine

Jessica Erin Biddinger, Purdue University

Abstract

Postnatal overeating and other perinatal nutritional manipulations may lead to a predisposition to develop obesity and related disorders as adults. Alterations to central nervous system pathways, including hypothalamic regulators and the sympathetic nervous system have been shown to contribute to these disorders. Previous research has shown that rats raised in small litter sizes exhibited an association between increased meal size and predisposition to obesity. Because meal termination depends heavily on vagal feedback from the gastrointestinal (GI) tract to the brain, it was hypothesized that disruption of these afferents by early postnatal overnutrition could also contribute. To test this hypothesis, overnutrition was induced by culling C57BL/6 mice on the day of birth to create litter sizes that were overfed (SL) and litters that were fed normally (NL) and the effects on meal size and other meal parameters were examined in young adult mice (age 3-4 mo) before significant differences in body weight developed. Meal pattern data were collected 18 hr/day for 3 weeks using a balanced diet. After these studies (age 6-8 mo) vagal GI afferents of each mouse were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion. After 24 hours, mice were perfused, and subcutaneous, retroperitoneal, and gonadal fat pads were removed and weighed. The anterior 8 cm of small intestine was stained with TMB and the density of vagal intraganglionic laminar endings (IGLEs), mechanoreceptors involved in detection of muscle stretch and contraction and control of GI motility, was determined for mice of each litter size. Mice from SL exhibited a small, but significant increase in daily food intake (11%) compared to mice from NL that was due to a combination of small trends, including increased meal number, size, and duration, and decreased intermeal interval. Mice from SL also had a significantly lower satiety ratio (20%), suggesting a given amount of food produced less satiety as compared to NL mice. Also at this age the structure of intestinal IGLEs appeared qualitatively similar in mice from both litter sizes, and IGLE density was similar (NL: 1306 ± 108/cm2; SL: 1388 ± 165/cm2). An unexpected finding for which we have found no precedent was that females of both litter sizes showed a substantial (54%) increase in intestinal IGLEs compared to males (males: 1123 ± 90/cm2; females: 1691 ± 142/cm2. Although some meal parameter trends associated with overnutrition were consistent with altered vagal afferents, changes in the CNS or peripheral organs could also account for them. The present results suggest that small but significant changes in food intake and satiety ratio can be detected as early as 3-4 months of age and differences in body weight and fat pad weight emerge by 6-8 months.

Degree

M.S.

Advisors

Fox, Purdue University.

Subject Area

Neurosciences|Psychobiology|Physiological psychology

Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server
.

Share

COinS