BackgroundIncreased 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.MethodThis 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.ResultsFatty 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.ConclusionThese 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.

Exposure to maternal obesity during early development programmes adverse metabolic health in rodent offspring. We assessed the relative contributions of obesity during pregnancy and suckling on metabolic health post-weaning. Wistar rat offspring exposed to control (C) or cafeteria diet (O) during pregnancy were cross-fostered to dams on the same (CC, OO) or alternate diet during suckling (CO, OC) and weaned onto standard chow. Measures of offspring metabolic health included growth, adipose tissue mass, and 12-week glucose and insulin concentrations during an intraperitoneal glucose tolerance test (ipGTT). Exposure to maternal obesity during lactation was a driver for reduced offspring weight post-weaning, higher fasting blood glucose concentrations and greater gonadal adiposity (in females). Males displayed insulin resistance, through slower glucose clearance despite normal circulating insulin and lower mRNA expression of PIK3R1 and PIK3CB in gonadal fat and liver respectively. In contrast, maternal obesity during pregnancy up-regulated the insulin signalling genes IRS2 , PIK3CB and SREBP1-c in skeletal muscle and perirenal fat, favouring insulin sensitivity. In conclusion exposure to maternal obesity during lactation programmes offspring adiposity and insulin resistance, overriding exposure to an optimal nutritional environment in utero , which cannot be alleviated by a nutritionally balanced post-weaning diet.

Exposure to maternal obesity during early-life can have adverse consequences for offspring growth and adiposity. We aimed to assess the relative contributions of exposure to maternal obesity, induced by a highly varied cafeteria diet, during pregnancy and lactation on these measures in rat offspring prior to weaning. Female Wistar rats were fed either a control (C) or cafeteria diet (O) for 8 weeks before mating, throughout pregnancy and lactation. Offspring were cross-fostered at birth to a dam on the same (CC,OO) or alternate diet prior to birth (CO,OC). Feeding a cafeteria diet based on 40 different foods, was associated with a sustained period of elevated energy intake before birth and during lactation (up to 1.7-fold), through increased sugar, total fat and saturated fat intake, and lower protein consumption. Cafeteria fed dams sustained greater weight than animals fed a control chow diet and greater perirenal adiposity by the end of lactation. Exposure to obesity during pregnancy was associated with lower offspring birth weight and body weight in early-postnatal life. In contrast, exposure during lactation alone reduced offspring weight but increased adiposity in male CO offspring before weaning. This research highlights that exposure to maternal obesity during lactation alone can programme adiposity in a sex specific manner.

Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) have been shown to inhibit lipogenesis and adipogenesis in adult rats. Their possible early life effects on offspring fat deposition, however, remain to be established. To investigate this, female Wistar rats (n = 6–9 per group) were fed either a 9:1 ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) or a lower 1:1.5 ratio during pregnancy and lactation. Each ratio was fed at two total fat levels (18% vs. 36% fat w/w) and offspring were weaned onto standard laboratory chow. Offspring exposed to a 36% fat diet, irrespective of maternal dietary LA:ALA ratio, were lighter (male, 27 g lighter; female 19 g lighter; p < 0.0001) than those exposed to an 18% fat diet between 3 and 8 weeks of age. Offspring exposed to a low LA (18% fat) diet had higher proportions of circulating omega-3 LCPUFA and increased gonadal fat mass at 4 weeks of age (p < 0.05). Reduced Srebf1 mRNA expression of hepatic (p < 0.01), gonadal fat (p < 0.05) and retroperitoneal fat (p < 0.05) tissue was observed at 4 weeks of age in male and female offspring exposed to a 36% fat diet, and hepatic Srebf1 mRNA was also reduced in male offspring at 8 weeks of age (p < 0.05). Thus, while offspring fat deposition appeared to be sensitive to both maternal dietary LA:ALA ratio and total fat content, offspring growth and lipogenic capacity of tissues appeared to be more sensitive to maternal dietary fat content.