Sex Differences in Long-term Metabolic Effects of Maternal Resveratrol Intake in Adult Rat Offspring

Abstract Maternal nutrition can affect the susceptibility of the offspring to metabolic disease later in life, suggesting that this period is a window of opportunity for intervention to reduce the risk of metabolic disease. Resveratrol, a natural polyphenol, has a wide range of beneficial properties including anti-obesogenic, anti-atherosclerotic, and anti-diabetic effects. We previously reported that maternal resveratrol intake during pregnancy and lactation has early metabolic effects in the offspring with these effects at weaning depending on the type of diet ingested by the mother and the offspring’s sex. Here we analyzed whether these metabolic changes are maintained in the adult offspring and if they remain sex and maternal diet dependent. Wistar rats received a low-fat diet (LFD; 10.2% Kcal from fat) or high fat diet (HFD; 61.6% Kcal from fat) during pregnancy and lactation. Half of each group received resveratrol in their drinking water (50 mg/L). Offspring were weaned onto standard chow on postnatal day 21. Maternal resveratrol reduced serum cholesterol levels in all adult offspring from HFD mothers and increased it in adult female offspring from LFD mothers. Resveratrol increased visceral adipose tissue (VAT) in LFD offspring in both sexes but decreased it in male HFD offspring. Resveratrol shifted the distribution of VAT adipocyte size to a significantly higher incidence of large adipocytes, regardless of sex or maternal diet. These results clearly demonstrate that maternal resveratrol intake has long-lasting effects on metabolic health of offspring in a sex specific manner with these effects being highly dependent on the maternal diet.