Abstract
BACKGROUND: Increased consumption of linoleic acid (LA, omega-6) in Western diets coupled with the pro-inflammatory and adipogenic properties of its derivatives has led to suggestions that fetal exposure to this dietary pattern could be contributing to the intergenerational cycle of obesity. METHOD: This study aimed to evaluate the effects of maternal consumption of a LA to alpha-linolenic acid (ALA) ratio similar to modern Western diets (9:1) compared to a lower ratio (1:1.5) on placental and fetal growth, and to determine any cumulative effects by feeding both diets at two total fat levels (18% vs 36% fat w/w). Female Wistar rats (n = 5-7/group) were assigned to one of the four experimental diets prior to mating until 20d of gestation. RESULTS: Fatty acid profiles of maternal and fetal blood and placental tissue at 20d gestation were different between dietary groups, and largely reflected dietary fatty acid composition. Female fetuses were heavier (2.98 ± 0.06 g vs 3.36 ± 0.07 g, P < 0.01) and male placental weight was increased (0.51 ± 0.02 g vs 0.58 ± 0.02 g, P < 0.05) in the low LA:ALA groups. Female fetuses of dams exposed to a 36% fat diet had a reduced relative liver weight irrespective of LA:ALA ratio (7.61 ± 0.22% vs 6.93 ± 0.19%, P < 0.05). These effects occurred in the absence of any effect of the dietary treatments on maternal bodyweight, fat deposition or expression of key lipogenic genes in maternal and fetal liver or maternal adipose tissue. CONCLUSION: These findings suggest that both the total fat content as well as the LA:ALA ratio of the maternal diet have sex-specific implications for the growth of the developing fetus.
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Key Points
Previous studies have shown that the high omega-6:omega-3 ratio in the modern Western diets is reflected in the blood and tissue fatty acid profiles of pregnant and lactating women, as well as breast milk, however, the effect of perinatal exposure to an increased omega-6:omega-3 PUFA ratio remains unclear. Increasing omega-6 PUFA intake induced a gradual enhancement in fat mass over generations. However, the level of LA (~ 19% energy) and LA:ALA ratio (28:1) in this study were much higher than those found in typical Western diets, and the impact of different dietary fat levels was not evaluated. In addition, no studies to date have examined the effects of an increased maternal omega-6:omega-3 ratio on maternal, placental and fetal outcomes before birth.
The aim of the current study was to determine the effects of increasing the LA:ALA ratio (9:1 vs 1:1.5), in the diet of rats, on maternal weight gain, placental and fetal growth and the expression of lipogenic and adipokine genes in maternal and fetal liver and maternal adipose tissue. To determine any additive effects of altering the maternal dietary LA:ALA ratio each diet was fed at either 18% fat w/w, to reflect dietary recommendations of fat intake, or at a higher fat content of 36% fat w/w.
The results of the current study demonstrate that varying the fat content and LA:ALA ratio in the diet during pregnancy results in significant shifts in the fatty acid profile of the dam, placenta and fetus in late pregnancy with dietary LA:ALA ratio eliciting potentially sex-specific effects on placental and fetal weights. Importantly, these effects occurred in the absence of any impact of dietary LA:ALA ratio on maternal energy intake, bodyweight or fat deposition. Doubling the fat content of these experimental diets had the expected impact on maternal food and energy intake but was not associated with any significant alterations in maternal, placental or fetal weights or maternal fat deposition.
The study demonstrated that both the total amount of fat and the ratio of LA and ALA in the maternal diet have significant effects on placental and fetal weight, supporting the hypothesis that the quality, as well as the quantity, of fat in the maternal diet can impact on fetal growth and development. Importantly, the LA:ALA ratio in the current study was designed to reflect that of typical Western diets of many countries, and our results show that consuming this high LA diet was associated with alterations in placental and fetal weight in comparison to a LA:ALA ratio considered to be ‘optimal’ for human nutrition. The observed changes in placental and fetal weight may contribute to future metabolic and physiological function of the offspring, given the established association between reduced fetal and placental growth and increased future risk of obesity and poor metabolic health. However, further studies are required in order to determine the longer-term impacts of maternal dietary LA;ALA ratio and total fat load on the growth, body composition and cardiometabolic health of the offspring. Human studies that have assessed the potential implication of a higher omega-6:omega-3 ratio and/or elevated maternal omega-6 intakes on growth, body composition or metabolic health of the children are also limited and further studies (or re-evaluation of existing studies) are needed. The results of the current study have also demonstrated that at least some of the effects of maternal dietary fat load/LA:ALA ratio elicited sex-specific responses, which may in part be due to differences in the placental response to omega-3 LCPUFA between male and female placentas.