Breastfeeding duration modifies the association between maternal weight status and offspring dietary palminate oxidation

Authors: DIAZ, EVA - Arkansas Children'S Nutrition Research Center (ACNC); WILLIAMS, DAVID - Arkansas Children'S Nutrition Research Center (ACNC); COTTER, MATTHEW - Arkansas Children'S Nutrition Research Center (ACNC); SIMS, CLARK - Arkansas Children'S Nutrition Research Center (ACNC); WOLFE, ROBERT - University Arkansas For Medical Sciences (UAMS); ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC); BORSHEIM, ELISABET - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/5/2022
Publication Date: 4/11/2022
Citation: Dias, E.C., Williams, D.K., Cotter, M., Sims, C.R., Wolfe, R.R., Andres, A., Borsheim, E. 2022. Breastfeeding duration modifies the association between maternal weight status and offspring dietary palminate oxidation. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqac097.
DOI: https://doi.org/10.1093/ajcn/nqac097

Interpretive Summary: Children born to women with excessive weight are prone to develop obesity and other metabolic disorders which increase their chance of adverse events in adulthood (i.e., heart attack, stroke). Animal studies show that offspring born to mothers with obesity favor the storage of dietary fat over utilization. The process of using fat from the diet to produce energy is called dietary fat oxidation (DFO). Evidence regarding the impact of maternal obesity on offspring DFO in humans is lacking. Human studies with controlled measurements over long periods represent the best option to assess DFO in the context of maternal programming of offspring metabolism. This is because factor such as maternal gestational weight gain, early life nutrition, and parenting styles can modify offspring metabolism as well therefore these factors must be taken into consideration. The purpose of this study was to evaluate the association between maternal weight and DFO in 2-year-old children taking into consideration other factors that may influence this outcome. The GLOWING is a longitudinal observational study conducted at the Arkansas Children’s Nutrition Center. Women (n=55) with normal (NW) and excessive (EW) weight were enrolled early or before pregnancy. Physical activity was measured at enrollment using accelerometers, weight gain was measured at the research facility. Composition of human milk was measured at 6 months post-partum. Feeding practices, breastfeeding duration, etc., were assessed throughout the first two years of life. At age 2, parental feeding practices were assessed, and DFO measured using stable isotopes which allowed direct measurement of dietary fat utilization by the body. Contrary to our hypothesis, DFO was 50% higher in offspring born to women with excessive weight compared to women with normal weight. Further analyses showed that breastfeeding duration was an important determinant in this finding. Specifically, children born to women with EW had higher DFO compared to children born to women with NW provided that they were breastfed for at least 9 months. We measured the association of human milk components and offspring DFO. We found that DFO increased with increasing concentrations of hormones (leptin, insulin) in human milk. These hormones are known to be elevated in the milk of women with EW. Interestingly, maternal physical activity early in pregnancy, parental feeding restriction practices at age 2 years, dietary quality, and male sex associated with higher DFO in children. All in all, our data indicate that the association between maternal weight and offspring DFO is modified by breastfeeding duration. In addition, obesity – induced compositional changes in human milk hormones are involved in this finding. Importantly, our study identified maternal physical activity early in pregnancy as a factor that increases offspring DFO. This may indicate that exercise in early pregnancy may favorably modify physiological responses in the offspring directly associated with fat deposition and utilization. In addition, boys had higher DFO compared to girls. These data highlight the importance of studying both sexes in metabolic research, as sexual differences apparent even in early childhood.

Technical Abstract: Offspring of obese rodents develop a metabolic phenotype that favors fat deposition over dietary fat oxidation (DFO). Data regarding the impact of maternal obesity on offspring fuel usage in humans is scarce. The objective of this study was to evaluate the association between maternal weight and DFO in 2-year-old children considering potential confounders and modifiers. Women (n=55) were enrolled by the 1st trimester of gestation. Maternal physical activity (PA, accelerometers) at enrollment, and gestational weight gain (GWG), were measured. Offspring sex, race, birthweight, and breastfeeding (BF) duration were self-reported. Human milk (HM) composition was determined at 6 months post-partum. At age 2 years, dietary quality (healthy eating index, HEI) as well as parental feeding practices (Child Feeding Questionnaire, CFQ) were assessed. Offspring DFO (%/h) was measured using deuterated palmitic acid (2H31-palmitate). Generalized linear regression analysis was used to model the associations between offspring DFO, maternal weight status [normal weight (NW), vs. excessive weight (EW)] and other variables of interest. DFO was 50% higher in the EW vs. the NW group (p = 0.03). Maternal weight interacted with BF duration in association with DFO (p = 0.04). Specifically, DFO increased with increasing BF duration, but only in the EW group. To explore mechanisms related with this finding, associations between HM components and DFO were measured. DFO increased with increasing HM insulin and leptin concentrations. PA early in pregnancy, parental feeding restriction, and male sex positively associated with DFO while HEI negatively associated with DFO. The association between maternal weight and offspring DFO at age 2 years was modified by breastfeeding duration. HM insulin and leptin concentrations seem to contribute to DFO. There was sexual dimorphism in DFO. Modifiable factors such as maternal PA in as well as parental feeding restriction associated with higher rates of DFO.