Abstract
Maternal prenatal undernutrition predisposes offspring to higher adiposity in adulthood. Mechanisms involved in these programming effects, apart from those described in central nervous system development, have not been established. Here we aimed to evaluate whether moderate caloric restriction during early pregnancy in rats affects white adipose tissue (WAT) sympathetic innervation in the offspring, and its relationship with adiposity development. For this purpose, inguinal and retroperitoneal WAT (iWAT and rpWAT, respectively) were analyzed in male and female offspring of control and 20% caloric-restricted (from 1–12 d of pregnancy) (CR) dams. Body weight (BW), the weight, DNA-content, morphological features and the immunoreactive tyrosine hydroxylase and Neuropeptide Y area (TH+ and NPY+ respectively, performed by immunohistochemistry) of both fat depots, were studied at 25 d and 6 m of age, the latter after 2 m exposure to high fat diet. At 6 m of life, CR males but not females, exhibited greater BW, and greater weight and total DNA-content in iWAT, without changes in adipocytes size, suggesting the development of hyperplasia in this depot. However, in rpWAT, CR males but not females, showed larger adipocyte diameter, with no changes in DNA-content, suggesting the development of hypertrophy. These parameters were not different between control and CR animals at the age of 25 d. In iWAT, both at 25 d and 6 m, CR males but not females, showed lower TH+ and NPY+, suggesting lower sympathetic innervation in CR males compared to control males. In rpWAT, at 6 m but not at 25 d, CR males but not females, showed lower TH+ and NPY+. Thus, the effects of caloric restriction during gestation on later adiposity and on the differences in the adult phenotype between internal and subcutaneous fat depots in the male offspring may be associated in part with specific alterations in sympathetic innervation, which may impact on WAT architecture.
Highlights
A crescent body of evidence has demonstrated that hormonal, metabolic and nutritional disturbances at a critical, sensitive period of early life may determine the propensity to the development of obesity and its related metabolic pathologies [1,2,3]
We show for the first time that moderate caloric restriction during the first part of pregnancy leads to a reduced noradrenergic innervation of the subcutaneous white adipose tissue (WAT) in the offspring, suggesting that nutrition during gestation can modulate peripheral nervous system development
We show that the effects produced by this caloric restriction on adipose tissue innervation are gender
Summary
A crescent body of evidence has demonstrated that hormonal, metabolic and nutritional disturbances at a critical, sensitive period of early life may determine the propensity to the development of obesity and its related metabolic pathologies [1,2,3]. Long lasting effects of maternal undernutrition have been observed on enteric sympathetic nervous system (SNS) in the offspring; 50% maternal caloric restriction during the last two weeks of pregnancy reduced enteric sympathetic innervation [9], and norepinephrine (NE) levels in the coeliac-superior mesenteric ganglion complex and the diameter of its neurons [10]. These findings suggest that the development of sympathetic innervation could be affected by nutritional disturbances during critical periods of development and be responsible for some of the lasting effects of these conditions
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