Hyperlipidic diet affects body composition and induces anxiety-like behaviour in intrauterine growth-restricted adult mice.

Abstract

What is the central question of this study? What is the effect in male and female offspring of a protein-deficient diet producing intrauterine growth restriction (IUGR) in maternal mice on morphometric, metabolic and behavioural parameters before and after a challenge with a fat diet? What is the main finding and its importance? Male and female mice presented different growth trajectories after birth. IUGR favoured increased adiposity in male mice, and high-fat diet-induced anxiety-like behaviour in female mice. As there is sexual dimorphism in the response to maternal manipulations, we aimed to analyse the effects of intrauterine growth restriction (IUGR) in both sexes on morphometric, metabolic and behavioural parameters throughout postnatal development, and after challenge with a hyperlipidic diet. Female Swiss mice (n=59) were distributed into two groups (SD: standard diet, n=26; and PDD: isocaloric protein-deficient diet, n=33), 2weeks before mating and during the gestational period. After birth, offspring from SD and PDD dams were cross-fostered and nurtured by SD dams until postnatal day (PND) 28. At PND 60 all animals were challenged with a hypercaloric diet for 4weeks. Offspring birth weight was significantly reduced in the PDD group compared to the SD group (P=0.0001), but only male offspring presented a rapid catch-up during the first 21days of development. Although no differences in body weight were observed between groups after the challenge with the hyperlipidic diet, an increase in the relative perigonadal white adipose tissue (P=0.009) and a decrease in gross gastrocnemius muscle weight (P=0.010) were observed in the PDD males. In relation to behavioural tests, there was an increase in locomotion in both sexes (P=0.0001), and a decrease in female grooming (P=0.006) in the PDD group. Additionally, females from the PDD group showed increased hyperlipidic food intake. In conclusion, IUGR affected both sexes, with females showing prominent behavioural modifications and males presenting altered body composition elicited by a hyperlipidic diet.