Maternal Dietary Ethanol Consumption Is Associated With Hypertriglyceridemia in Adult Rat Offspring
Authors: Pennington J. S. , Shuvaeva T. I. , Pennington S. N. 
Published: April 2006

Background: The consumption of significant amounts of alcohol (ethanol, EtOH) may markedly increase serum triglyceride levels. This study describes a significant increase in fasting serum triglyceride (TG) levels in adult male rats whose mothers consumed EtOH. The hypertriglyceridemia occurred although the offspring never directly consumed EtOH and had consumed only rat chow for the preceding 14 months. Furthermore, both male and female adult offspring had an additional, significant increase in TG levels if their mothers consumed EtOH and experienced stress (restraint) during the pregnancy.Methods: Harlan‐derived Sprague Dawley® female rats were dosed during pregnancy with EtOH via a liquid diet, and their offspring were compared with offspring of mothers who were either fed ad libitum or pair‐fed the liquid diet without EtOH. At birth, the offspring of EtOH mothers exhibited no visible abnormalities except reduced weight, and all offspring were surrogate fostered within 48 hr of birth to mothers who had consumed commercial rat chow throughout their pregnancy. After weaning, all offspring consumed only commercial rat chow, and they were examined over the next 14 months for changes in triglyceride homeostasis as a function of maternal alcohol intake.Results: Adult male offspring of mothers that consumed EtOH during their pregnancy had significant increases in fasting serum triglycerides associated with an increase in the very low density lipoprotein serum fraction. Acute administration of insulin to the offspring of all maternal dietary groups resulted in a rapid clearing of the serum triglycerides, and there were no differences in basal or heparin‐releasable lipoprotein lipase activity between any of the progeny. Castration of the male offspring of EtOH‐treated mothers prevented the development of elevated TG levels. Administration of testosterone to littermate female offspring increased circulating TG levels compared with testosterone‐treated offspring of pair‐fed mothers. EtOH‐consuming mothers who also underwent five periods of restraint‐induced stress (approximately 10 min each session) produced offspring whose fasting serum TG levels were higher than those whose mothers consumed EtOH but experienced no restraint or who experienced restraint but no EtOH. Maternal stress significantly reduced lipoprotein lipase activity in some offspring treatment groups, but the changes did not correspond to changes in the serum TG levels of the offspring. That is, maternal restraint‐induced stress was associated with a loss of heparin‐releasable lipoprotein lipase activity by male progeny from pair‐fed and EtOH‐fed mothers and the female offspring of ad libitum‐fed and EtOH‐fed mothers.Conclusions: Although serum triglycerides increased with age in all offspring, the increase was much more pronounced in the progeny of mothers who consumed EtOH during their pregnancy. The hypertriglyceridemia was significantly more pronounced in the male offspring and in female offspring treated with testosterone. Castration of male offspring inhibited the hypertriglyceridemia development, which suggests that male sex hormones may play a role in the development of this condition. Maternal EtOH consumption coupled with maternal restraint‐induced stress significantly increased the level of hypertriglyceridemia in both male and female offspring compared with offspring whose mothers experienced restraint but no EtOH or EtOH with no restraint. If this study models the human condition, the results could represent an unrecognized risk factor in a number of adult disease states hypothesized to be associated with hypertriglyceridemia, such as cardiovascular disease, hypertension, and diabetes.