Effects of litter size and diet composition on the development of some lipogenic enzymes in the liver and brown adipose tissue of the rat.

Male Sprague-Dawley rats were reared in litters of nine (normal litters) or 18 pups, and the dams were fed either a low fat (control) or a high fat diet. Offspring from each litter size and diet group were separated from the mothers on postnatal d 30, subdivided into two groups each, and fed either the control or the high fat diet until postnatal d 77. Hepatic glucose-6-phosphate dehydrogenase, malic enzyme and ATP-citrate lyase activities in the offspring from large litters were elevated during the early stages of weaning but later lagged behind enzyme activity of the normal litters. Brown adipose tissue enzymes also surged earlier in rats from large litters but did not fall below the values attained by the normal litters until postnatal d 32. Enzyme activities on postnatal d 77 revealed that large litter size and high fat feeding during or after weaning were associated with diminished hepatic enzyme activities. Hepatic glucose-6-phosphate dehydrogenase and ATP-citrate lyase activities also showed significant positive interaction between litter size and diet composition after weaning. Large litter size was also associated with diminished brown adipose tissue enzymes in the mature rats, but the composition of the weaning diet did not independently exert long-lasting changes in this tissue. Nevertheless, there was a positive interaction between litter size and diet composition during and after weaning. The data suggest that neonatal undernourishment can exert a long-term influence on the metabolic profiles of the animal, and that diet plays a role in modulating this influence.

In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin.

The effects of smoking, aspirin ingestion, and sex differences on bleeding times and bleeding time thromboxane B2 and 6-keto-prostaglandin (PG)F1 alpha production were examined. Nonsmoking men produced more thromboxane B2 (3.99 +/- 0.76 ng/ml) than nonsmoking women (2.13 +/- 0.24 ng/ml). Female smokers produced more thromboxane B2 (5.01 +/- 0.97 ng/ml) than nonsmoking women. Twenty-four hours after a single dose of 600 mg aspirin, in vitro production of thromboxane B2 in response to collagen fell by 95%, whereas in vivo production of thromboxane B2 and 6-keto-PGF1 alpha in bleeding time blood fell by 87% and 66%, respectively. Subjects with the lowest absolute levels of thromboxane B2 24 hours after aspirin were also those with the longest postaspirin bleeding times. Recovery of 6-keto-PGF1 alpha production was faster than recovery of thromboxane B2 production, but 6-keto-PGF1 alpha production for most subjects was still below basal 72 hours after aspirin. The influence of two different doses of long-term aspirin (80 mg every other day and 325 mg daily) on the in vivo production of thromboxane B2 and 6-keto-PGF1 alpha was studied in normals and diabetics. After 14 days of 80 mg aspirin every other day, thromboxane B2 and 6-keto-PGF1 alpha production were both substantially inhibited (93% and 78%, respectively). After 14 days of 325 mg aspirin daily, thromboxane B2 production was similarly substantially inhibited (93%), whereas 6-keto-PGF1 alpha was significantly less affected (only 45% inhibition). Study of a second group of five normal subjects confirmed that 6-keto-PGF1 alpha production was significantly inhibited 24 hours after the first dose of 325 mg aspirin but was not significantly less than basal after 14 days of 325 mg aspirin. The results suggest that 325 mg aspirin daily is more antithrombotic compared with 80 mg every other day due to the superior preservation of prostacyclin production.