1. Possible associations between maternal nutrition in pregnancy and non-communicable diseases of adulthood were assessed using a rat model. Rats were habituated to diets containing a range of protein levels (18, 12, 9 and 6% by weight), over a 14 day period, before mating. The low protein diets were maintained throughout pregnancy. Lactating mothers and their offspring were transferred to a standard chow diet (20% protein). 2. Pregnant rats demonstrated a graded response to the diets, with those fed 9 and 6% protein tending to consume less energy and gain less weight than 18% protein fed controls. Litter size and newborn death rates were not significantly altered by the low protein diets. 3. Offspring of 12 and 9% protein fed dams were grossly normal, gaining weight at a similar rate to those born to 18% protein fed control rats. Offspring of the 6% protein fed dams were smaller than pups from all other groups, over a 21 week period. 4. At 9 weeks of age, systolic blood pressure was determined in the offspring. All offspring from the three low protein groups were found to have significantly elevated blood pressure (15-22 mmHg) relative to the control group. An inverse relationship between maternal protein intake and the systolic blood pressure of the offspring was observed. Blood pressure remained elevated in the offspring of the 9 and 6% protein fed dams until 21 weeks of age. The observed hypertension was associated with increased pulmonary angiotensin-converting enzyme activity in the low protein groups.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of RU 486 (mitepristone), an antagonist of type II glucocorticoid receptors (GR), on the development of obesity in young 5-wk-old obese fa/fa rats has been investigated. After 15 days of treatment, body composition of obese RU 486-treated rats was similar to that of lean-vehicle rats. Analysis of body composition changes showed that RU 486 effectively reversed the obesity. It stopped fat deposition in obese rats but increased protein deposition to the level of lean-vehicle rats. RU 486 prevented the development of hyperphagia and reduced gross energetic efficiency in the obese rats but had little effect on lean rats. Brown adipose tissue mitochondrial GDP binding was increased in obese rats but was reduced in lean rats by RU 486 treatment. RU 486 also reduced the elevated activity of hippocampal glycerophosphate dehydrogenase, a glucocorticoid-responsive enzyme, of obese rats to the level of lean rats. The evidence suggests that abnormal activity of glucocorticoid GR receptors or abnormal cellular responsiveness to corticosterone receptor complexes may be important in the development of obesity in the fa/fa rat.
The immune system has been previously demonstrated to be under the influence of maternal nutrition in pregnancy. Assessment was made of the effects of low protein diets (12, 9 and 6 g casein/100 g diet) fed before conception and during pregnancy on the immune system of the resulting offspring in early adulthood. Control animals were fed a diet containing 18 g casein/100 g. At the end of pregnancy all dams were fed a nonpurified diet containing 18.3 g protein/100 g. Male pups were weaned onto this diet, which they consumed until the age of 7 wk. Rats exposed to 18 g casein/100 g diet in utero mounted a typical acute phase response following E. coli endotoxin challenge at age 7 wk. Food intake was 75% lower, hepatic zinc concentrations 25% greater, and serum albumin 15% lower than in saline-injected controls. Pulmonary glutathione levels were 35% greater in endotoxin-treated rats than in saline-treated controls. In rats exposed to low protein diets in utero the trend was for the acute phase response to be blunted. This was most noticeable with respect to the anorectic response, hepatic zinc uptake and pulmonary glutathione uptake. In rats not challenged with endotoxin, maternal diet had pronounced effects on tissue zinc status at the age of 7 wk. Liver zinc concentrations were 21% and 16% lower in the groups exposed to 9 and 6 g casein/100 g diets relative to the control group exposed to 18 g casein/100 g diet. Glutathione status was altered in all groups exposed to low dietary protein in utero.(ABSTRACT TRUNCATED AT 250 WORDS)
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