Programming effects of an early-life diet containing large phospholipid-coated lipid globules are transient under continuous exposure to a high-fat diet

Breastfeeding is associated with a lower risk of developing obesity during childhood and adulthood compared to feeding infant milk formula (IMF). Previous studies have shown that an experimental IMF (eIMF; comprising Nuturis®), programmed mouse pups for a lower body weight and fat mass gain in adulthood when challenged with a high-fat diet (HFD), compared to a control IMF (cIMF). Nuturis has a lipid composition and structure more similar to breastmilk. Here, the long-term effects were tested of a similar eIMF, but with an adapted lipid composition, and a cIMF, on body weight, glucose homeostasis, liver and adipose tissue. Nutrient composition was similar for the eIMF and cIMF; the lipid fractions comprised ~50% milkfat. C57BL/6JOlaHsd mice were fed cIMF or eIMF from postnatal (PN) day 16-42 followed by a HFD until PN168. Feeding eIMF versus cIMF in early life resulted in a lower body weight (-9%) and body fat deposition (-14%) in adulthood (PN105). The effect appeared transient, as from PN126 onward, after 12 weeks HFD, eIMF-fed mice caught up on controls and body and fat weights became comparable between groups. Glucose and energy metabolism were similar between groups. At dissection (PN168), eIMF-fed mice showed larger (+27%) epididymal fat depots and a lower (-26%) liver weight without clear morphological aberrations. Our data suggest the size and coating but not the lipid composition of IMF fat globules underlies the programming effect observed. Prolonged exposure to a HFD challenge partly overrules the programming effect of early diet.