Safety of n-3 PUFAs during pregnancy and effects on the metabolic phenotype of the offspring

Abstract

Maternal obesity is the strongest predictor of obesity in the offspring, as it leads to alterations in metabolism in the offspring, perpetuating obesity across the generations. Obese pregnancy is characterised by inflammation and exaggerated insulin resistance, which cause excess transfer of nutrients to the fetus. As omega-3 fatty acids (n-3 PUFAs) are insulin sensitising and antiinflammatory they may counteract this effect. Thus, supplementing n-3 PUFAs in overweight and obese pregnancy might improve metabolism and body composition of the children. In addition, supplementing oxidised fish oil to rats during pregnancy led to greater newborn mortality. As supplements are often oxidised, there is a need to determine the safe dose of oxidised fish oil during pregnancy. The central hypothesis in this thesis is that n-3 PUFAs supplementation in overweight and obese pregnancy will improve metabolism and lower body fat percentage in the offspring. Four predictions were tested: 1) n-3 PUFA supplementation will improve the insulin sensitivity of mothers in overweight or obese pregnancy 2) and will improve the metabolism and body composition of their infants 3) maternal n-3 PUFAs will ameliorate the adverse metabolic effects of a maternal highfat diet on the offspring through alterations in gene expression in metabolic tissues 4) the toxicity of oxidised fish oil in pregnancy will be dose related. I utilised a double-blinded randomised controlled trial to investigate the effect of n-3 PUFA supplementation in overweight and obese women during pregnancy and lactation on the body composition of the offspring. n-3 PUFA supplementation did not lower the body fat percentage in the infants or affect insulin sensitivity during pregnancy. However, it reduced the triglyceride levels in mothers during pregnancy and in the infants. In the animal model of insulin resistant pregnancy (maternal high-fat diet), supplementation with unoxidised fish oil prevented the development of insulin resistance in the offspring and partially ameliorated the adverse effects of high-fat diet on the hepatic metabolism. A human-relevant dose of a highly oxidised oil increased neonatal mortality in rats, but no adverse effects were seen of oils oxidised within recommended limits, suggesting that risk is low for women consuming store-purchased fish oil.