Associations between maternal adiposity and appetite-regulating hormones in human milk are mediated through maternal circulating concentrations and might affect infant outcomes

Abstract

BackgroundAppetite-regulating hormones (ARH) in human milk (HM) are suggested to affect infants’ milk intake and possibly infant growth. Maternal adiposity might contribute to higher levels of ARH in HM, either from the mammary gland or from raised circulating levels due to higher adiposity. Counterfactual-based mediation analysis can define indirect and direct effects between HM ARH and maternal and infant factors, and might be an important tool when investigating the mother-milk-infant triad.ObjectiveWe aim to investigate whether potential associations between (1) maternal adiposity and HM ARH and (2) HM ARH and infant milk intake and growth are mediated through maternal and infant plasma ARH, respectively.Materials and methodsMaternal and infant anthropometry and body composition, HM and blood samples were collected from 223 mother-infant dyads participating in the Mother, Infant and Lactation Quality study at three postpartum visits from 1 to 8.49 months. Leptin, insulin and adiponectin were analyzed using immunoassays. Mediation analyses using linear mixed-effect models were applied to investigate the direct and indirect effects through maternal and infant plasma hormone concentrations.ResultsA positive association between maternal body-mass-index (BMI) and HM leptin was mediated by maternal plasma leptin by 29% when fixing BMI to < 25 kg/m2, and through 51% when fixing BMI to ≥ 25 kg/m2 (pinteraction < 0.01). There was no mediated effect through plasma insulin in the association between BMI and HM insulin (p = 0.068). We found negative and positive associations between HM insulin and total milk intake and infant weight, respectively, however, these diminished in mediation analyses with reduced sample sizes.ConclusionOur main results suggest that the association between maternal adiposity and HM leptin was mediated through circulating leptin to a stronger degree for mothers with overweight compared to mothers with normal-weight. This indicates that excess maternal adiposity, and the resulting rise of circulating leptin and possible concomitant low-grade inflammation, may be reflected in HM composition.Clinical trials registry numberNCT03254329.

Leptin receptor expression in blood mononuclear cells of lactating women is associated with infant body weight: Potential role as a molecular biomarker

“…Previous findings on this association have been unclear. Our results are consistent with other authors, 48,49 but on the other hand, a positive association with maternal BMI 18,19 and adiposity or fat mass 18,28,50 has also been reported. The association of plasma and milk insulin with infant growth has not been as extensively studied as for leptin.…”

“…Human milk is a biological fluid characterized by a wide variation of metabolite and hormone contents. 14,15 The presence of leptin and insulin in milk is well documented, 16,17 their concentration correlates with maternal plasma levels [18][19][20] and varies depending on population characteristics and maternal lifestyle, diet and health status. 14,15 Insulin is believed to be actively transported into milk by mammary epithelial cells, 19,20 and leptin is produced in adipose tissue and mammary epithelial cells.…”

Gestational Diabetes Mellitus and Colostral Appetite-Regulating Adipokines

“…The available data [86,89] indicate that adipokine concentrations might be related to milk maturation stages and, because of this, Ça giran Yilmaz and Özçelik [90] found a positive relationship between the first month milk leptin level and the mother's anthropometric measurements (weight and BMI), but not with the newborn's weight. Similar to our findings, other authors [91] did not find any associations between either milk leptin or adiponectin but found that maternal BMI was positively associated with milk leptin and insulin. Despite the fact that determinations of leptin and adiponectin levels in biological material are valuable, the leptin/adiponectin ratio has a higher diagnostic accuracy as a marker of insulin resistance and metabolic syndrome [92][93][94].…”

“…Recently, Jara et al [105] stated that even such a non-obvious factor as race affects adiponectin and leptin levels throughout pregnancy. Overall, appetite-regulating adipokines in human milk are suggested to affect newborn's and infants' milk intake and possibly offspring growth [91,106,107]. According to Adamska-Patruno and coworkers [108], the shift in the balance between serum ghrelin and other appetite-regulating hormones affects energy homeostasis [109][110][111].…”

The Effects of FABP4 on Cardiovascular Disease in the Aging Population

“…DNA methylation acts as a mediator between transient adverse environmental factors in early life and metabolic health risk in adulthood [103]. In humans, FABP4 has been shown to vary during lactation and shows strong correlations with adiponectin and leptin in breast milk [104], and maternal adiposity and breast milk composition may be linked to infant growth [105]. At the same time, weight trajectories in individuals with different polygenic risks for obesity start to diverge in early life [106], and the effects of an obesogenic environment on health are most pronounced in those with a genetic predisposition [106,107].…”