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Diabetes and Endocrinology - Pediatrics and Child Health

Neonatal Overfeeding Induced by Small Litter Rearing Causes Altered Glucocorticoid Metabolism in Rats
Published: Friday, November 04, 2011
Author: Miao Hou et al.

by Miao Hou, Yanhua Liu, Lijun Zhu, Bin Sun, Mei Guo, Jonas Burén, Xiaonan Li

Elevated glucocorticoid (GC) activity may be involved in the development of the metabolic syndrome. Tissue GC exposure is determined by the tissue-specific GC-activating enzyme 11ß-hydroxysteriod dehydrogenase type 1 (11ß-HSD1) and the GC-inactivating enzyme 5a-reductase type 1 (5aR1), as well as 5ß-reductase (5ßR). Our aim was to study the effects of neonatal overfeeding induced by small litter rearing on the expression of GC-regulating enzymes in adipose tissue and/or liver and on obesity-related metabolic disturbances during development. Male Sprague-Dawley rat pup litters were adjusted to litter sizes of three (small litters, SL) or ten (normal litters, NL) on postnatal day 3 and then given standard chow from postnatal week 3 onward (W3). Small litter rearing induced obesity, hyperinsulinemia, and higher circulating corticosterone in adults. 11ß-HSD1 expression and enzyme activity in retroperitoneal, but not in epididymal, adipose tissue increased with postnatal time and peaked at W5/W6 in both groups before declining. From W8, 11ß-HSD1 expression and enzyme activity levels in retroperitoneal fat persisted at significantly higher levels in SL compared to NL rats. Hepatic 11ß-HSD1 enzyme activity in SL rats was elevated from W3 to W16 compared to NL rats. Hepatic 5aR1 and 5ßR expression was higher in SL compared to NL rats after weaning until W6, whereupon expression decreased in the SL rats and remained similar to that in NL rats. In conclusion, small litter rearing in rats induced peripheral tissue-specific alterations in 11ß-HSD1 expression and activity and 5aR1 and 5ßR expression during puberty, which could contribute to elevated tissue-specific GC exposure and aggravate the development of metabolic dysregulation in adults.