Effects of litter size on sympathetic activity in young adult rats

Abstract

Young, James B. Effects of litter size on sympathetic activity in young adult rats. Am J Physiol Regulatory Integrative Comp Physiol 282: R1113-R1121, 2002 10.1152/ ajpregu.00139.2001.-Rearing animals in small litters induces a permanent increase in body weight and body fat. To determine whether changes in sympathoadrenal activity contribute to this effect, litter size was adjusted the day after birth and maintained until weaning at 21 days. Sympathetic nervous system (SNS) activity was measured in adult animals using 3 H]norepinephrine; nervous system activity; sympathoadrenal function POSTNATAL EXPERIENCE AFFECTS the development of numerous components of the mammalian nervous system. Visual and auditory pathways (11,15,26) as well as somatosensory and olfactory systems (2, 29) are dependent on sensory input for normal maturation. The sympathoadrenal system is also susceptible to environmental influences during development. For example, early exposure to a hot environment affects the development of sudomotor function (7), whereas neonatal exposure to cool temperatures induces hyperplasia in sympathetic efferent pathways to brown adipose tissue (16). Moreover, neonatal handling (brief, daily separation of mothers and pups between birth and weaning) leads to diminished sympathetic nervous system (SNS) activity in spleen and heart and to exaggerated adrenal medullary responsiveness to fasting in adult male rats (30).The size of the litter in which an animal is reared represents another neonatal manipulation with potential implications for SNS development. Rats reared in large litters accumulate less [3 H]norepinephrine ([ 3 H]NE) in the heart after subcutaneous injection of tracer than animals reared in smaller litters (12). Similarly, cardiac NE concentrations are inversely related to litter size at 15 days of age, although not at weaning (10). Finally, cardiac and renal NE levels are lower at 40 days of age in rats reared in large litters than in those reared in smaller litters (24). However, the consequences of litter size for sympathoadrenal function (in contrast to tissue NE levels) in adult animals has not been examined.Rearing animals in small litters has long been known to increase body size, an effect that has been attributed to neonatal "overnutrition" (14,20,28). Because rearing in small litters has been employed in several experimental models of obesity or hypertension (1, 3,9,13,19), the possibility arose that developmentally acquired alterations in sympathoadrenal function might contribute to the increased susceptibility to obesity or hypertension in these animals. Because neonatal overnutrition is commonly followed by overfeeding after weaning, the relative contributions of litter size and the postweaning diet are not always clear. Consequently, these studies were undertaken to examine specifically the impact of litter size alone on the regulation of SNS activity.

Developmental origins of obesity: a sympathoadrenal perspective

“…Although both male and female animals reared in large litters displayed the stimulatory effect of sucrose on cardiac SNS activity which has been reported repeatedly over the years, 49,55-59 rats reared in small litters did not. 35 The absence of cardiac sympathetic stimulation by dietary sucrose seen in rats reared in small litters is similar to a previous observation from this laboratory in adult mice following treatment with gold thioglucose, 60 a neurotoxin which destroys neurons within the ventromedial hypothalamus. Gold thioglucose-treated mice do not exhibit dietary changes in SNS activity in heart and IBAT seen in untreated animals.…”

“…53,54 The impact of litter size on SNS function in young adult animals was reported several years ago from this laboratory. 35 Although the animals reared in small litters were bigger than those reared in large litters, the impact on tissue NE levels (adjusted for differences in wet weight of tissue) was noted in some, but not all tissues. Of particular note in these studies, however, was the observation that the SNS response to dietary sucrose differed markedly in the two rearing groups.…”

“…33 Finally, changes in fetal or neonatal nutrition owing to the presence of maternal diabetes or variations in litter size, respectively, also exert effects on SNS development. 34,35 The effects associated with exposure to these environmental factors are not uniform. As the SNS is composed of numerous function-specific subdivisions, 36 however, development of each subunit is likely influenced by its own set of environmental factors.…”

Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat

“…Slight differences were found at 4 months of age. In addition, there was no difference in litter size between the two strains (7 6 2 for A/J and 7 6 1 for B6), which excludes the possible influence of litter size on sympathetic nervous system development of the pups (28).…”

Neonatal Programming of Neuroimmunomodulation – Role of Adipocytokines and Neuropeptides

“…It was recently shown that young adult humans that were born with low birth weight showed increased sympathetic activity that could contribute to hypertension [128] . One model often employed to manipulate neonatal nutrition is variation in litter size [129] . Animals reared in small litters are considered to be 'overnourished', whereas those reared in large litters are 'undernourished'.…”