The effects of varying maternal dietary fat quantity and composition on disease programming in the offspring: a focus on essential fatty acids

Draycott, Sally Anne Victoria (2020) The effects of varying maternal dietary fat quantity and composition on disease programming in the offspring: a focus on essential fatty acids. PhD thesis, University of Nottingham.

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The nutritional environment that an individual is exposed to during development has been shown to affect growth and fat deposition as well as disease risk in later life. In particular, the effects of a maternal diet high in fat are relatively well characterised in animal models and are typically associated with a range of offspring phenotypes, including high blood pressure, increased adiposity and impaired insulin and glucose homeostasis. These high-fat diets often contain high amounts of saturated fatty acids (SFA), however, changes in dietary recommendations over the past 60 years have resulted in increased consumption of vegetable oils. As such, dramatic increases in the intake of omega-6 polyunsaturated fatty acids (PUFA), specifically linoleic acid (LA), have been observed in Western populations. This increase in omega-6 fatty acid consumption has not been matched by an increase in the intakes of omega-3 fatty acids, which has remained stable over this period of dietary change. The effect of this dietary pattern on offspring risk of obesity and cardiometabolic disturbance is yet to be established, however, studies have demonstrated a pro-adipogenic effect of omega-6 fatty acids suggesting increases in the intake of LA may be linked to the increasing prevalence of obesity.

Broadly, this research aimed to elucidate the effects of a maternal dietary LA to alpha-linolenic acid (ALA; omega-3) ratio similar to that consumed in the Western diet (9:1) compared to a proposed ‘ideal’ ratio of 1:1.5, on offspring growth, fat deposition and potential markers of cardiometabolic disturbance. Due to the increasing amount of women of reproductive age consuming a high-fat diet and, since total dietary PUFA intake also influences PUFA metabolism, we also investigated the effect of feeding each dietary fat ratio at either 18% fat w/w (in line with dietary recommendations) or at a higher fat level of 36% fat w/w. A rat model was utilised to achieve the study objectives by allowing for tight control of dietary manipulation as well as invasive end points.

The main findings of this research have demonstrated that a low LA:ALA ratio in the diet was effective at increasing circulating levels of long chain omega-3 PUFA, specifically eicosapentaenoic acid (EPA), in the dams which was largely reflected in the offspring. However, improving the omega-3 status of the offspring had no discernable beneficial effect on adiposity during early-life. In fact, a maternal low LA, low fat diet was associated with increased fat mass in the offspring. Whether the fluctuations in the lipogenic capacity of tissues observed in these studies in the offspring during early-life is indicative of later metabolic disturbance remains to be established. Further to this, a maternal high fat diet, irrespective of the LA:ALA ratio, was associated with a 15% reduction in bodyweight in both male and female offspring when compared to a low fat diet (P<0.0001). This was independent of any maternal weight gain and was persistent throughout early-life.

Finally, maternal consumption of a high LA, high fat diet was associated with significant upregulation of genes associated with cholesterol packaging and transport across the placenta. This implicates the placenta as a potential mechanistic mediator of the effects of maternal diet on offspring health. This hypothesis was also tested in pregnant women of different body mass index (BMI) classifications. In women, however, maternal BMI was associated with fewer inconsistent alterations in gene expression. However, the absence of nutritional intake data from these participants was a limitation of the study and comparability to rodent data.

In summary, the results of this thesis indicate that the adipogenic effects previously associated with omega-6 fatty acids do not appear to be contributing towards increased risk of adiposity in offspring when consumed in the maternal diet. The capacity for early-life alterations in tissue function and structure to elicit long-term consequences for individuals remains to be established and should be a focus of future studies. However, a maternal high fat diet, where the predominant fat source was not saturated fats, still elicited unfavourable outcomes in the offspring despite no evidence of increased weight gain or adiposity in the mothers. This has the potential to impact on recommendations to expectant mothers around reducing the quantity of fat within their diet even if it has not had any unfavourable phenotypic effects on the individuals themselves. Future studies should consider more mechanistic approaches however, the preliminary investigations in this thesis highlight the placenta as a likely contributor to the observations between maternal diet and offspring health.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Langley-Evans, Simon C
Elmes, Matthew J
Muhlhausler, Beverly S
Keywords: Pregnancy, Fatty acids, Developmental origins, Obesity, Nutrition, Omega-3, Omega-6, Maternal diet, Developmental programming
Subjects: Q Science > QP Physiology > QP501 Animal biochemistry
Faculties/Schools: UK Campuses > Faculty of Science > School of Biosciences
Item ID: 59988
Depositing User: Draycott, Sally
Date Deposited: 31 Jul 2020 04:40
Last Modified: 24 Jul 2022 04:30

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