Prenatal essential fatty acid deficiency in mice results in long-term gender-specific effects on body weight and glucose metabolism

Abstract

Abstract. Essential fatty acids are important for normal growth and development in early life. However, the long-term effects of prenatal essential fatty acid deficiency (EFAD) on the adult metabolism remain to be determined. The aim of this study was to investigate the effects of an EFAD diet given to mice during late gestation on body weight and body composition, and metabolism in the adult offspring. Pregnant dams were given an EFAD or a control diet during the last 10 days of gestation. After delivery, all mice were fed normal chow and the body weight of the offspring was measured weekly. Furthermore, food intake, energy expenditure and intraperitoneal glucose tolera nce were analysed in the adult offspring in addition to body composition (analysed by dual-energy X-ray absorptiometry), plasma levels of leptin, triglycerides and cholesterol. The body weight was lower in the EFAD offspring as compared to the controls during the first 4 weeks of age, and remained lower in the females throughout the study. Lean body mass and plasma leptin levels were also lower in the female EFAD offspring as compared to the controls. Male EFAD offspring were found to have higher fasting glucose and insulin levels as well as higher insulin levels during the glucose tolerance test compared to the controls. However, no differences were found in blood lipids, food intake or energy expenditure between EFAD and control mice of either gender. These results demonstrate that an EFAD diet given during the last 10 days of gestation results in long-term gender-specific effects on body weight and insulin sensitivity in the adult offspring. IntroductionMaternal nutritional status during pregnancy and lactation is a significant factor in the adult health of the offspring. The combination of inadequate nutrition early in life and overnutrition later in life is thought to increase the risk of obesity and associated metabolic disorders such as type 2 diabetes (1). Essential fatty acids are required for normal growth and development in early life, and deficiency in humans results in growth retardation during the neonatal period (2). Low plasma levels of essential fatty acids have been observed in children with malnutrition (3-5), and in preterm infants (6). However, essential fatty acid deficiency (EFAD) in humans rarely occurs in isolation, but is common in general undernutrition or in dietary protein deficiency. Therefore, experimental animal models are useful to separate the specific long-term effects of EFAD from those of undernutrition and protein malnutrition.Adult rats subjected to EFAD from perinatal life and onwards had decreased body weight, but increased insulin levels before and during a glucose tolerance test to which these rats were subjected (7). In diabetes-prone BB rats, an EFAD diet commencing at 10 weeks of age reduced the incidence of autoimmune diabetes, and this reduction was associated with the depletion of omega-6 fatty acids (8). Metabolites of omega-6 fatty acids, such as prostaglandin E 2, are known to suppress glucose-...

An Increased Dietary Supply of Medium-Chain Fatty Acids during Early Weaning in Rodents Prevents Excessive Fat Accumulation in Adulthood

“…To test our hypothesis, the offspring of two rodent species, C57Bl/6j mice and Wistar rats, were used; both of which are commonly used models to study metabolic programming [16,17,18,19,20]. The experimental design, intended to expose offspring to increased MCFA levels during lactation and early post-weaning, would enable us to selectively investigate the importance of early dietary FA composition during a critical period for WAT development [21].…”

Perinatally Imposed Essential Fatty Acid Deficiency Changes Renal Function of the Adult Rat

“…The reduced birth weight and the lower body weight gain during development were a characteristic effect of EFAD [19] [20]. To reduce body weight, there is evidence that EFAD leads to increased basal metabolism [21] [22], although its actual mechanism is not yet known.…”

Perinatal programming by diets with essential fatty acid deficient/high saturated fatty acids or different n‐6/n‐3 ratios for diseases in adulthood

“…In mice, given the EFA deficient/high saturated fat diet only during second half of pregnancy, the birth weight of the offspring was lower than in the control group and remained so in the female offspring to adulthood at 15 weeks of age . The dams were switched to ordinary chow at delivery, so the offspring was mainly raised on milk from normally fed dams and continued ordinary chow after weaning.…”

“…Intraperitoneal glucose tolerance test (IPGTT) at 12 weeks of age showed that both gender had a similar glucose tolerance as controls but the male offspring from the experimental group had higher fasting insulin and glucose and a significantly higher insulin production up to 60 min after injection, while the females had a completely congruent insulin curve to that of the controls . The study has limitations since the pups were influenced by the dam's changed metabolism at the start of the lactation period and were not followed as long as the animals in the other studies, making comparisons difficult.…”